A 71-year-old type II diabetic, smoker, and hypertensive Caucasian male patient presented to the surgical service of our hospital for evaluation of splenomegaly and pancytopenia. A laboratory workup found that he had anemia (hematoglobin 7.0 g/dL), leukopenia (white blood count 2.19 k/μL), thrombopenia (platelets 50 k/μL), and hypoalbuminemia (3.1 g/dL). He complained of upper left abdominal pain but denied fever, chills, nausea, or vomiting. A physical exam revealed no lymphadenopathy, but his left upper quadrant of the abdomen was tender on palpation, and splenomegaly was observed. An upper gastrointestinal endoscopy showed an esophageal polyp, which by pathological examination revealed Barrett's esophagus with high-grade dysplasia and evolving invasive adenocarcinoma. Due to his symptomatology, and the concern of the possible spread of either cancer, he underwent transhiatal esophagectomy, splenectomy, and cholecystectomy. He was found to have splenic pleomorphic MCL and esophageal adenocarcinoma by pathological examination. His MCL international prognostic index, which consists of age, performance status, LDH level, and leukocyte count, was 7 out of 11 points, placing him in the high-risk category. In this category, his median survival, from the time of diagnosis, would be predicted to be less than 3 years []. This would later turn out to be accurate. The patient did not have a bone marrow biopsy for lymphoma staging. Thus, his karyotype status was unavailable. The patient did not go through further chemotherapy in our oncology clinic after the operation. Follow-up for over 6 months by the surgical oncology was focused on the treatment of his postsurgical esophageal stenosis. The patient was subsequently lost to follow-up, but one year later, at another hospital, he presented with recurrent bouts of aspiration pneumonia. Radiology and bronchoscopy examinations revealed a right lower lobe lung mass. The endobronchial biopsy revealed soft tan tissues at 0.7 × 0.6 × 0.2 cm in aggregate, which turned to be poorly differentiated squamous cell carcinoma of the lung. Staging positron emission tomography (PET) scan found the lung mass at 9 cm in the greatest dimension and the tumor metastasis to the right clavicle, lower trapezius muscle, and regional lymph nodes. It was determined he had stage IV pulmonary squamous cell carcinoma. 10 days after one cycle of chemotherapy, he was hospitalized for incontinence and severe back pain. Magnetic resonance imaging (MRI) showed spinal lytic lesions at the levels of T8 and L4. During the hospitalization, he developed streptococcal bacteremia, which resulted in his port-a-cath being removed. Despite the second round of chemotherapy after discharge, the patient expired shortly thereafter.
The gross examination of his splenectomy specimen revealed a massive spleen that weighed 2639 grams and measured 30 × 19 × 9 cm. The splenic parenchyma exhibited homogeneous congested cut surfaces without overt nodularity. A splenic hilar lymph node at 1.3 cm in diameter was also dissected. A 4.2 × 3.8 × 0.4 cm partially circumferential, granular, tan-red ulcerated mass was found in the lower third of the esophagus which proximally displaced the Z-line. Some small lymph nodes in the esophageal adventitia and gastric serosa were identified. The gallbladder was morphologically normal. The microscopic study of the spleen displayed a diffuse involvement of the red pulp by a large lymphoid cell population with irregular nuclear contours and conspicuous nucleoli (). The splenic hilar lymph node demonstrated a total effacement of the architecture by the neoplastic lymphoid cells with a similar appearance to those in the red pulp. Ancillary testing performed on sections from the splenic tumor cells demonstrated strong immunoreactivity for CD20 (), PAX5, CD5 (), and BCL2; partial reactivity for CD23 (), CD45, BCL1 (), and SOX11 (); and negativity for AE1/AE3, BCL6, CD10, c-MYC, MUM1, p53, and S-100. The tumor cell proliferation index was at 30-40% by Ki-67 staining. The splenic lymphoma revealed BCL1/CCND1 break-apart signals in 41% tumor cells, using a locus-specific probe (LSI BCL1 Dual Color Break Apart, Abbott Molecular, Abbott Park, IL) for BCL1/CCND1 on 11q13 (). BCL1/IGH translocation fusion signals were detected in 65% tumor nuclei using probes for the CCND1 gene at 11q13 and the immunoglobulin heavy chain gene at 14q32 (Integrated Oncology, Phoenix, AZ) (). Both the CCND1 and IGH genes showed two to four copy numbers in lymphoma cells. The esophagus was affected by a poorly differentiated adenocarcinoma infiltrating into the submucosal layer (). The adenocarcinoma arose from Barrett's esophagus with high-grade dysplasia (). Fourteen lymph nodes in the periesophageal and perigastric connective tissue were negative for metastatic carcinoma or mantle cell lymphoma. The pathologic stage for the esophageal adenocarcinoma was pT1b, pN0, which correlates to a stage 1B cancer. The esophageal adenocarcinoma exhibited strong staining for AE1/AE3 (), BCL1 (), and p53 and was negative for synaptophysin and CD56. The FISH for the BCL1/CCND1 gene performed on the esophageal tumor showed aneuploidy in 24% of the tumor cells scored (), without gene rearrangement or break-apart signals for the CCND1 gene. Microscopic examination of his subsequent endobronchial lung biopsy one and a half years later revealed poorly differentiated squamous cell carcinoma predominantly in sheeting patterns that had pleomorphic nuclei and dense cytoplasm, with occasional keratinized cells noted. Some of the tumor cells were clustered in an acinar fashion. Immunohistochemical staining showed the lung tumor cells were positive for BER-EP4, CK5/6, CK7, CK19, and p63 and negative for CD56, CK20, chromogranin, Napsin A, synaptophysin, and TTF-1. Despite extensive communication with the hospital that had diagnosed and treated the patient's pulmonary squamous cell carcinoma, the patient's pathological imaging and additional tissue materials could not be obtained due to federal restrictions. For this reason, our discussion focuses almost exclusively on the synchronous MCL and esophageal adenocarcinoma as described.


A 34-year-old male patient was brought to the emergency department after a road traffic accident, probably due to force dorsiflexion of the left foot while tiptoeing as the patient tried to gain balance of a stumbling two wheeler and eventually the bike fell on the foot. On examination, swelling and tenderness was noted on the dorsal aspect of left foot. Toe movements of all four lesser toes were painful. Movements of the ankle worsened the pain at the lesser four metatarsophalangeal joints. Plain radiographs of the left foot revealed dorsolateral dislocation of metatarsophalangeal joints of all four lesser toes of the left foot (Figure ). Patient was taken up for emergency reduction of the joints and under spinal anaesthesia closed reduction was tried with toe traps for all four lesser toes. Three such attempts by different surgeons failed. Under tourniquet control, open reduction of four lesser metatarsal joints was performed using two 3 cm longitudinal incision over second and fourth metatarsal joints respectively. Extensor tendons identified and retracted. Interposition of capsule and longitudinal breach of plantar plate by metatarsal head were noted, which prevented the closed reduction. Reduction of the joint was then performed by incising the plantar plate, capsule was repaired. The steps were then repeated for the other three lesser toes. Congruent joint reduction was then confirmed under C-arm (Figure ). The joint was stable and reduction maintained without any need for stabilization. Postoperatively a below-knee splint with dorsal re-enforcement in neutral position at metatarsophalangeal joints was given. Dressing was changed on day four and suture removal was done on day 14. Patient was in below-knee slab for four weeks (Figure ). Progressive weight bearing was started (Figure , ) and patient was reviewed at three and six months and two years (Figure -). Patient was ambulatory without any pain and recurrence.


A 28-year-old South Asian male with no relevant past medical history presented with six months history of dry cough and fever. His cough was worse at night, associated with night sweats and 16 kg unintentional weight loss. It had worsened dramatically with shortness of breath on mild exertion and fever with chills 15 days prior to the patient seeking medical attention. He also noticed difficulty in taking steps around one month ago that progressively worsened to involve weakness in lower limbs around the same time his cough worsened.
On examination, he was found to have generalized muscle wasting and was cachectic, he had bilateral foot-drop (Figure ) as he was walking with a high steppage gait. He also had clubbing with left axillary and supraclavicular lymphadenopathy. The chest exam revealed reduced air entry on the left side with crepitations in the right lung base. Neurological exam initially was significant for loss of dorsiflexion and weak plantar flexion bilaterally with preserved ankle reflexes. Throughout his hospital stay, his neuropathy progressed with further loss of plantar flexion and ankle reflex with additional loss of pain sensation in his feet.
The patient was admitted to an isolation unit; first set of COVID testing was positive detected by reverse transcription-polymerase chain reaction (RT-PCR), his chest X-ray showed miliary shadowing (Figure ). Additionally, he had hypochromic microcytic anemia and lymphocytopenia (Table ). The patient was initiated on COVID protocol. Further evaluation showed vitamin B12 deficiency with iron stores depletion, elevated serum ferritin, and D-dimer level. HIV was nonreactive. Assessment for TB started with QuantiFERON and sputum for TB (i.e., acid fast bacilli and TB PCR), the patient was treated empirically initially with anti-TB therapy due to high clinical suspicion and chest X-ray findings despite the first set of sputum testing negative for acid fast bacilli. Mycobacterium tuberculosis was detected by PCR after repeated sets of sputum samples as bronchoscopy was delayed due to COVID-19 pandemic concerns. High resolution CT of the chest showed typical features for miliary TB (Figure ).
Peripheral neuropathy initially was attributed to vitamin B12 deficiency, but vitamin B12 replacement showed no improvement instead there was progression of his neuropathy. MRI spine did not show intraspinal, spinal cord, or thecal abnormalities. Nerve conduction study/electromyography (NCS/EMG) done at the time showed severe active sensorimotor axonal distal polyneuropathy with the involvement of bilateral posterior tibial and peroneal motor nerves, severe involvement of bilateral superficial peroneal sensory nerves, and mild involvement of right median and ulnar palmer sensory nerves and bilateral sural sensory nerves (Table ).
The patient was discharged after getting one month of anti-TB treatment and kept on close follow-up. At six weeks he was contacted over the phone (using telehealth consultation) and as per him his gait and sensations had improved and he could now move his foot upwards. Unfortunately, he was lost to follow-up at eight weeks as he had left the country for good.


First case
A 29-year-old male presented with a year history of right cheek mass that was gradually increasing in size. A superficial parotidectomy was initially done in another hospital, and subsequently, was diagnosed as adenocarcinoma. He was presented to our institution with residual disease. Computed tomography (CT) with contrast revealed an ill-defined mass measuring 8.8 cm in greatest dimension in the right parotid gland with central necrosis. It was invading the overlying skin and bulging into the right neck space (Figure ). CT scans showed no radiological evidence of metastasis. Reviewing of his prior pathology showed a neoplasm predominantly comprised of small round blue cells arranged in solid nests and separated by fibrous stroma (Figure , B). Tumor nests were composed of monomorphic cells with indistinct cytoplasm and nuclei with finely granular chromatin, occasional prominent nucleoli and high mitotic rate (Figure ). Focal area of chondro-osseous differentiation was identified (Figure , D). Immunohistochemical staining showed positivity of tumor cells for P16, CK5/6, CK8/18, P63, CD99 (strong and diffuse membranous staining), PGP9.5, and focally for CK20, chromogranin and CD56. Synaptophysin was weakly positive and Ki67 showed >20% proliferation index (Figure ). However, tumor cells were negative for CDX2, TTF1, GFAP, CK7 and desmin (Table ). Based on the morphological and immunohistochemical features, FISH for EWSR1 gene rearrangement was performed, and positive results were obtained. EWSR1-FLI1 fusion transcript gene rearrangement was detected by RT-PCR confirming the diagnosis of ALES. Accordingly, the patient was treated with five cycles of chemotherapy. Post-treatment, the patient showed partial response in terms of tumor size. Subsequently, right radical parotidectomy with neck dissection was performed. Gross evaluation revealed a poorly demarcated nodular mass with white cut surface. Microscopic examination demonstrated the same histological features as diagnosed previously for ALES. The resection showed positive resection margins, angioinvasion and perineural invasion. Postoperatively, the patient received adjuvant chemotherapy and radiation therapy. Twenty-two months after the radical resection, the patient presented with local recurrence, multiple pelvic-abdominal deposits and spinal bone metastatic lesions. Patient was referred to palliative care for continuing symptomatic management.
Second case
A 46-year-old female presented with a history of swelling behind the right ear over the parotid area for two years. The case was a referral from outside hospital to our institution. She had a history of multifocal papillary thyroid microcarcinoma seven years before, for which a total thyroidectomy was done, and radioactive iodine was given. Radiologically, a solid mass measuring 2.0 cm in greatest dimension was identified, occupying the superficial lobe of the right parotid gland (Figure ). A right total parotidectomy with facial nerve and neck dissection were subsequently performed, and the specimen was submitted for pathologic evaluation. The referring hospital had diagnosed the patient with poorly differentiated carcinoma with neuroendocrine features. Microscopic examination of the outside slides, submitted to our institution for revision of diagnosis, demonstrated a nested basaloid proliferation infiltrating the gland parenchyma with significant fibrosis and desmoplasia (Figure , B). Tumor surrounded and extended into some salivary ducts but did not appear to originate from these ducts (Figure ). Tumor cells were monomorphic with fine chromatin and small prominent nucleoli. Some areas showed stippled salt and pepper chromatin reminiscent of neuroendocrine type of chromatin (Figure ). Occasional areas of focal necrosis, lymphovascular invasion and mitosis were also found (Figure ). Focal areas of pseudorosettes were evident. Occasionally, scattered cells with abundant eosinophilic cytoplasm, representing squamous differentiation, were seen (Figure ). A specimen submitted as fascial nerve was also found to be involved in the tumor. Immunohistochemically, tumor cells showed diffuse positivity for p63. However, CK5/6 and CD99 showed strong and diffuse membranous staining by the majority of tumor cells. Staining with synaptophysin showed patchy positivity (Figure ). Vimentin, chromogranin, TTF1, CD56, HER2, CD117, and CK7 were negative. (Table ). FISH for the EWSR1 gene rearrangement was positive in 100% of the nuclei (Figure ). Patient received concurrent chemo-radiotherapy cycles and travelled abroad to continue her treatment.


A 47-year-old nulliparous, virginal woman presented to the emergency department with a 2-day fever and acute abdominal pain. She also complained of a 2-month history of foul-smelling vaginal bleeding. She had pyrexia, with a temperature of 38°C (100.4°F), and marked tenderness of the whole abdomen. She has a past medical history significant for breast cancer, which was treated with six cycles of CAF (cyclophosphamide, [doxorubicin] Adriamycin, fluorouracil), adjuvant radiotherapy, and tamoxifen for 4 years; the doses are uncertain since she had taken those therapies in the other institutes. She has not had a gynecological evaluation for over 8 years since the end of her breast cancer treatment, and she had discontinued her tamoxifen.
Laboratory investigation demonstrated a hemoglobin level of 12.3 g/dL (normal range, 12–16 g/dL), a white blood cell count of 12,600/mm
3 (normal range, 4,000–10,000/mm
3) and a C-reactive protein of 157.9 mg/L (normal range, 0.1–5.0 mg/L). Mild elevation of her liver enzymes was observed, with a total bilirubin of 2.2 mg/dL (normal range, 0.2–1.4 mg/dL) and a direct bilirubin of 0.7 mg/dL (normal range, 0.0–0.5 mg/dL).
A dynamic CT scan of the liver was performed to evaluate for biliary infection as this patient had been known to have a history of gallbladder stones for years along with complaints of upper abdominal pain. The CT scan revealed a 16-cm uterine mass and increased free fluid in the pelvic cavity, including both paracolic gutters, the perihepatic space, and the perisplenic space. Consequently, she was referred to our obstetrics and gynecology department.
Transrectal ultrasonography showed a bicornuate uterus and an 18.6- × 9.1-cm mass with heterogeneous echogenicity within the left uterus. The mass appeared to extend through the cervix into the vaginal cavity. Its irregular-shaped margins and increased blood flow suggested the possibility of malignancy (
). Because her vital signs were stable (aside from fever), the patient received an oncological evaluation and antibiotic treatment before surgery. Since F-18 FDG were ordered and needed time to arrive, PET/CT were planned two days later, and the surgery was planned for the next day. Antibiotics (piperacillin 4g, tazobactam 0.5g, metronidazole 0.5g) were injected intravenous every 8 hours, and administered for about 48 hours until just before surgery.
Pelvic MRI was performed on the day after the patient’s initial presentation, revealed underlying uterus didelphys with an approximately 15- × 9- × 17-cm mass with mixed signal intensity in the lower abdominal area (
) and an approximately 6- × 2.7- × 3-cm mass of the left cervix and lower uterine body on T2-weighted imaging. These MRI findings suggested the possibility of hemoperitoneum or cancer peritonei due to rupture of (1) endometrial cancer, (2) uterine sarcoma, or (3) large myoma with degeneration.
A whole-body PET/CT scan was ultimately performed (two days after presentation) and showed an intensely hypermetabolic subserosal mass with accompanying hemorrhage and possible rupture; further, hypermetabolic peritoneal nodules and peritoneal infiltration with ascites were observed (
).
The patient underwent diagnostic laparotomy three days after presentation. Surgical exploration revealed a ruptured bicornuate uterus with a large mass within the left uterine horn (
). The mesentery of the small bowel and appendix were partially adhered to the uterine mass. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed, and invasive cancer implants within the bowel were removed. Estimated surgical blood loss was approximately 1500 mL.
Pathological analysis confirmed an undifferentiated uterine sarcoma with tumor size up to 23 × 13 × 6 cm. Because a tumor in her left fallopian tube and one of her bowel mass implants tested positive for cancer, she was diagnosed with FIGO Stage IIIA (from the International Federation of Gynecology and Obstetrics cancer staging system)
.
Postoperatively, the patient was treated with a combination of etoposide (150 mg/m
2 for 3 days), ifosfamide (1.5 g/m
2 for 3 days), and cisplatin (70mg/m
2 for 1 day) once every 3 weeks. Chest and abdomen CT were performed for follow up 2 weeks after. There were no sign of cancer recurrence in the chest and abdominal CT.


A 66-year-old obese female with essential hypertension, paroxysmal atrial fibrillation and atrial tachycardia was referred for a transesophageal echocardiogram prior to an elective electrophysiology study and ablation. On physical exam, she was morbidly obese with a body mass index of 37.7. Her cardiac exam was unremarkable with normal S1 and S2 heart sounds and absence of murmurs. The respiratory exam was unremarkable. Blood pressure and peripheral pulses were equal bilaterally. The chest X-ray was unremarkable. Mediastinum was within normal limits. Laboratory studies were unremarkable with the exception of mild normocytic anemia (hemoglobin of 10.2 g/dl).
Transthoracic echocardiography revealed a normal sized left ventricle with an estimated ejection fraction of 60–65%. The left ventricular wall thickness and diastolic parameters were normal. The right ventricle was dilated but demonstrated normal systolic function. The aortic root, sinotubular junction and ascending aortic diameters were within normal limits. The aortic valve was trileaflet with no significant regurgitation. No other significant valvulopathy was noted.
The patient underwent a transesophageal echocardiogram in the EP lab under general anesthesia with endotracheal intubation due to high risk neck anatomy. The study confirmed normal left ventricular parameters and no significant valvulopathy. The left atrial appendage velocity was normal on pulse doppler imaging. There was no LAA thrombus. Evaluation of the descending thoracic aorta revealed an additional echolucent lumen located posteriorly (, ). Color Doppler imaging demonstrated flow directed away from the probe (). Pulse wave Doppler was suggestive of venous flow (). A possible Stanford type B dissection in the descending thoracic aorta could not be excluded. No dissecting flap was noted in the ascending aorta. Additionally, a small sized atheroma was visualized in the proximal descending thoracic aorta. The patient underwent CT angiography for evaluation of suspected aortic syndrome.
CT angiography showed a normal descending aorta with no evidence of dissection, however it did reveal a dilated accessory hemiazygos vein (, , ). The left internal jugular and left subclavian were stenotic with a string-like appearance and there was an absent left brachiocephalic vein.


A 55-year-old male presented with worsening fatigue. Upon evaluation, he had leukocytosis (white blood cell count—103 × 109/L), thrombocytopenia (platelets—25 × 109/L), and anemia (hemoglobin—7.6 g/dL). Review of the peripheral blood smear revealed 57% circulating blasts, and flow cytometry was compatible with AML with monocytic features. Myeloblasts comprised 15% of cells and showed expression of CD13, CD33, CD117, CD34, HLA-DR, partial CD123, minimal CD64, CD38, and partial cMPO; the blasts were negative for CD56, CD15, CD11b/C, CD14, TdT, and B and T cell markers. There were around 8% immature monocytic cells present which expressed dim CD45, CD13, CD117, CD33, CD15, partial CD11b, and partial CD64 and were negative for CD34. There were also 14% mature monocytic cells.
A comprehensive bone marrow evaluation was diagnostic for acute myeloid leukemia involving a hypercellular bone marrow (100%) with decreased erythropoiesis, decreased megakaryopoiesis, increased eosinophils, 19% monocytes, and 24% blasts and promonocytes. Morphologically, the blasts appeared large, with irregular and convoluted nuclear contours, dispersed chromatin, and small amounts of basophilic cytoplasm. They were admixed with an increased number of promonocytes that had delicately folded nuclei, dispersed chromatin, inconspicuous nucleoli, and finely granulated cytoplasm. Importantly, there were increased eosinophils that had increased and coarse basophilic granules (). Flow cytometry evaluation of the bone marrow biopsy yielded a hemodiluted specimen with myeloblasts expressing CD34, CD13, CD33, CD117, and HLA-DR comprising 1.1% of total cells.
Conventional cytogenetics at diagnosis demonstrated two-related clones. Two metaphases had pericentric inversions of chromosome 16 (). The second related clone was observed in majority of the metaphases, and each had a Philadelphia chromosome with the classic (9;22) translocation along with an inversion 16 abnormality (). Fluorescence in situ hybridization (FISH) assays were positive for CBFB rearrangement and BCR/ABL1 translocation in 94.0∼95.0% of the interphase nuclei (Figures and ). A FISH assay for rearrangement of RUNX1T1/RUNX1 was normal ().
A qualitative reverse transcriptase polymerase chain reaction (RT-PCR) was positive for an e1a2 BCR-ABL1 fusion transcript coding for the 190 kDa BCR-ABL1 fusion protein. A hematologic neoplasm next generation sequencing (NGS) 141 gene panel that was obtained based on the first bone marrow reported only two mutations of unknown significance in TET2 (p.L1322R) and P2RY2 (p.V77A). There were no pathogenic variants detected for FLT3 exon 14 (internal tandem duplication), FLT3 exon 20 (tyrosine kinase domain), NPM1 exon 11, CEBPA, and KIT exon 17 p.D816V at a minimum allelic fraction of 1.0%.
The patient was initially treated with a 7 + 3 cytarabine-based induction regimen: seven daily doses of cytarabine (100 mg/m2) from day 1 to day 7, three daily doses of daunorubicin (90 mg/m2) from day 1 to day 3, and a single dose of Mylotarg (gemtuzumab ozogamicin, 4.5 mg/m2) on day 1. The detection of p190 BCR-ABL1 transcript at day 5 led to the addition of daily doses of 100 mg of dasatinib (tyrosine kinase inhibitor, TKI) from day 7 onwards. Intrathecal cytarabine therapy was omitted due to a low number of platelets. The patient was pancytopenic and needed multiple red blood cells and platelets transfusions. On day 14, peripheral blood showed severe pancytopenia and bone marrow showed a hypocellular (<5%) bone marrow with decreased trilineage hematopoiesis and 1% blasts. Although flow cytometry evaluation revealed a negative immunophenotypic study, FISH studies were positive for t(9;22) and inv(16) in 25.1–27.1% of the interphase cells. Conventional cytogenetics did not yield enough metaphases for a complete study. Dasatinib was stopped on day 21 due to persistent leukopenia. G-colony stimulating factor was given once on day 21 and on day 23. Notably on day 20, the patient's clinical course was complicated by a skin ulceration in his toes that later resulted in disseminated Fusarium infection (). Unable to obtain a bone marrow biopsy to evaluate for hematopoietic recovery, dasatinib was restarted on day 34. On day 45, peripheral blood was significant for absolute lymphopenia and monocytosis. Day 45 bone marrow biopsy showed a hypercellular marrow (80%), increased trilineage hematopoiesis, and less than 1% blasts. Flow cytometry on the same specimen was reported as a negative immunophenotypic study. The conventional cytogenetic study showed normal karyotype, and RT-PCR analysis for p190 BCR/ABL1 transcript was undetectable. His clinical status was in complete remission (CR), and the patient was eventually discharged on day 60.
Patient was kept on a continued daily dose of 100 mg of dasatinib. However, the patient had gradually increasing Fungitell values and eventually developed fulminant Fusarium infection. He was admitted for bilateral pneumonia on day 120 and was treated with amphotericin (5 mg/kg). He was later enrolled on a clinical trial for an alternative oral-based antifungal medication therapy. His fungal infection was reported to have improved with decreased pulmonary infiltrates and a healed foot wound. The patient returned on day 180 for bone marrow transplant evaluation. His peripheral blood smear was remarkable for pancytopenia and 9% circulating blasts. His bone marrow showed persistent AML with 64% blasts and blast equivalents involving a mildly hypercellular bone marrow (50–60%) with decreased trilineage hematopoiesis. The corresponding flow cytometry on the bone marrow specimen revealed 30% of aberrant myeloid blasts that were positive for CD45 (dim), CD34, CD117, HLA-DR, CD13, CD33, and CD38. Chromosome study showed complete resolution of the t(9;22) subclone (negative by FISH and RT-PCR); however, the inv(16) clone resurfaced with other additional abnormalities significant for clonal evolution (). Fungitell values were again high, and CT scan showed findings consistent with pneumonia and pansinusitis. Bronchial lavage cultures and blood cultures were negative for microorganism growth. Bone marrow hematopoietic stem cell transplantation (HSCT) was eventually contraindicated. The patient preferred hospice care and died two months after.


A 78-year-old man with a history of hepatitis C and surgical resection of HCC was followed up for end-stage renal disease (ESRD) due to diabetes. The patient’s medical history included hepatic steatosis, hypertension, diabetes mellitus type 2 and ESRD. He had been prescribed metformin, pantoprazole, enalapril, felodipine, metoprolol. The patient was a non-smoker and non-drinker. At the age of 74 years, the patient was introduced to our hospital for HCC surgery (). His physical examination on admission was unremarkable. Liver enzymes and function tests, namely bilirubin (0.44 mg/dL), albumin (4.0 mg/dL), and International Normalized Ratio (1.06) were within the normal range, while creatinine was slightly elevated at 1.74 mg/dL. The patient underwent right lobectomy of the liver for HCC, and dialysis was initiated after surgery. At 5 months after the hepatic resection, computed tomography and chest radiography revealed multiple tumors in the lung, indicating metastatic disease (). At that time, serum protein induced by vitamin K absence or antagonist II (PIVKA-II) was abnormally elevated (648 mAU/mL). The serum alpha fetoprotein (AFP) level was 5.7 ng/mL. The patient did not receive any anticancer therapy because of his ESRD and the advanced stage of HCC. We subsequently followed up on his natural course with serial imaging. Chest radiography revealed an increase in the size and number of lung metastases, and tumor markers were significantly elevated 4 months after recurrence (AFP, 1198 ng/mL; PIVKA-II, 214155 mAU/mL). However, 13 months after recurrence, the metastatic lesions suddenly decreased in size and number without receiving any specific treatment or herbal medicine (). Follow-up imaging showed no evidence of disease progression, and tumor makers were significantly decreased (AFP, <1.0 ng/mL; PIVKA-II, 46 mAU/mL) (). There were no signs of new lesions on imaging or an increase in tumor markers over 41 months after the recurrence.


A 30-year-old male with no medical history was admitted to the nearby hospital with a worsening cough and low-grade fever that had persisted for a month. Chest computed tomography (CT) revealed an abscess in the left lower lobe of his lung, and clinical laboratory tests showed elevated white blood cells of 13,200/μl (normal range, 4000–8000/μl) and C-reactive protein of 5.97 mg/dl (normal range, < 0.40 mg/dl). Treatment with sulbactam/ampicillin was initiated. Since no improvements were confirmed by the imaging and laboratory findings, antimicrobial treatment was changed to tazobactam/piperacillin on day 3 post admission, and was subsequently changed to meropenem (MEPM) on day 25 post admission. Treatment with voriconazole (VRCZ) was added on day 17 post admission because his β-D-glucan level reached to 123 pg/ml (normal range, < 20 pg/ml). However, it was discontinued 8 days later. Transbronchial biopsy and bronchoalveolar lavage performed to assess the mass did not detect malignancy or significant levels of bacteria, including mycobacteria and fungi. On day 27, the patient was referred to our tertiary center for further examination and treatment by specialists in respirology and infection and potential thoracic surgery. Since the definitive diagnosis could not be made, the patient was transferred to our hospital for further examination and treatment on day 27.
On admission, his vital signs were as follows: a body temperature of 36.6 °C, blood pressure of 120/66 mmHg, heart rate of 84 beats per minute, and a respiratory rate of 12 breaths per minute. The arterial oxygen saturation measured via pulse oximetry was 98% in the examination room. A physical examination including respiratory sound revealed no significant finding. Clinical laboratory tests showed that the patient had elevated C-reactive protein levels of 15.56 mg/dl (normal range, < 0.40 mg/dl) and his Aspergillus antigen test was positive (cut-off index of 3.5). Human immunodeficiency virus antibody and interferon-gamma releasing assay were negative. In addition, the β-D-glucan level decreased to a normal range (14.7 pg/ml). Chest X-ray and contrast-enhanced CT were performed on admission. Chest X-ray showed an infiltrative shadow in the left lower lung field (Fig. ), and CT showed a massive lesion in the left lower lobe of the lung, emphysematous changes, ectatic bronchi, and a nodular lesion that was thought to contain a mucoid impaction within its lingular segment. The bronchus was disrupted proximal to the mass lesion of the left lower lobe (Fig. a–c). Consequently, bronchial atresia in the inferior and anterior basal segments of the left lung was suspected based on imaging findings. Since the presence of a malignant lesion could not be excluded, bronchoscopy was performed on day 2 after transfer to our hospital. An endobronchial ultrasound-guided transbronchial needle aspiration was performed on the small mass lesion near the left second carina (Fig. d). The disrupted bronchus could not be confirmed via bronchoscopy because the disrupted site was located too peripherally. Histopathological analyses revealed no malignant findings, but presence of a filamentous fungus was indicated in Grocott staining (Fig. ). Although cultures did not detect any microorganisms, based on these findings, a lung abscess due to Aspergillus spp. was suspected. Therefore, VRCZ was reintroduced on day 9 after transfer. To perform treatment and confirm the suspected diagnosis of a lung abscess due to an Aspergillus infection, the patient underwent surgical resection of the lingular and basal segments of the left lung on day 22 after transfer. The abscess formation was macroscopically confirmed (Fig. ), and histopathological examination revealed emphysematous changes and ectatic bronchi within the lingular and left basal segments (Fig. a, b). These findings were compatible with bronchial atresia [], and no malignant lesions were confirmed. Although histopathological analyses did not reveal filamentous fungus, a tissue culture resulted in A. fumigatus growth. MEPM and intravenous VRCZ were continued for a total of 4 weeks and 3 weeks, respectively, and the patient was discharged on day 32 after transfer with continuing oral treatment with VRCZ. VRCZ was discontinued 5 months after the initiation of treatment because of poor medication compliance and the side effect of alopecia, and subsequent recurrence of the infection has not been confirmed.


A 79-year-old Japanese woman complained of blurred vision in her left eye presumably due to a pterygium-like tissue growth. She had a medical history of limbal dermoid from birth, which was removed at 12 years of age. Her decimal best-corrected visual acuity (BCVA) was 1.2 oculus dexter and 0.5 oculus sinister (OS) with hyperopia. Slit-lamp microscopy revealed a markedly thick growth of pterygium-like triangular ocular surface tissue from the temporal conjunctiva toward the apex of the cornea. Corneal opacity was observed around the head of the tissue OS (Fig. a). Because of visual impairment with a severe irregular astigmatism, we performed pterygium surgery and ocular surface reconstruction. Eight months after the operation, her BCVA improved to 0.8 OS without obvious recurrence of the lesion (Fig. b).


We report a case of a 40-year-old man who presented with 7 days history of visual disturbance, leg weakness, pain, and unsteadiness. He reported seeing “spots” in his visual fields, double vision, and some retro-ocular pain. He described burning pain in his right thigh and proximal weakness of his right leg which restricted his daily activities. However, he was fully independent on presentation.
He had a medical history of relapsing-remitting multiple sclerosis for the last 15 years for which he was currently on monthly natalizumab for the last 9 years and received a total of 107 infusions over this period. Past disease-modifying therapies for multiple sclerosis (MS) included beta interferon and glatiramer acetate which were switched due to recurrent relapses. His serology for John Cunningham virus (JCV) was positive since 2012 as shown in Fig. .
He also had epilepsy for last 10 years, with a seizure semiology of partial with secondary generalized tonic-clonic seizures. He was on 4 anti-epileptics: levetiracetam 4gm/day, lamotrigine 600 mg/day, carbamazepine 700 mg/day, phenobarbitone 105 mg/day. The other regular medications included fesoterodine 8 mg, pyridoxine 100 mg, and vitamin D 2400 units daily.
His pertinent examination findings were horizontal nystagmus with diplopia in central and right gaze without any restriction in the eye movements. The right leg had reduced power grade in hip adduction, abduction, and flexion 4/5. His reflexes in bilateral lower limbs were 3+ with bilateral extensor plantar responses. There was past pointing on the right finger to nose test.
It was suspected that his current symptoms may be due to MS relapse. He was started on intravenous methyl prednisolone 1 g/day, and MRI brain was done as shown in Fig. (day 1). The MRI brain prompted further investigation due to the atypical location and radiological features of the lesion including a lumbar puncture and CSF analysis for JCV-DNA PCR. Results received 3 days later showed a JCV viral load of 6620 copies/ml. Another lumbar puncture was done to further confirm the results 5 days that showed a viral load of 48,300 copies/ml.
He was started on mirtazapine at 60 mg daily doses. Cidofovir 5 mg/kg per dose, two doses 1 week apart followed by fortnightly doses a total of 6 doses over 12 weeks were administered. Mefloquine was considered but due to the potential of causing seizures in our patient was not commenced.
The clinical course is summarized in Table over a 6 months period from PML onset to his transfer to a rehabilitation facility. Over this course, he deteriorated from being functionally independent to being wheel chair bound. There was a major deterioration in weeks 7–15 before his clinical condition stabilized and later improved with a major morbidity.


A 35-year-old woman presented with history of weakness, metrorrhagia and exertional dyspnea was referred to hematology department. Lab tests revealed leukocytosis (27.7 × 109 /L), anemia (hemoglobin:9.2 g/dl), and thrombocytopenia (56 × 109/L). Peripheral blood smear showed abnormal monocytic cells with significant number of blast (50%) that suggestive of acute leukemia. A diagnosis of AML-M4 was made based on bone marrow aspiration, as acute leukemia with differentiation along both myeloid and monocytic lines were observed (Fig. ) and also flow-cytometry result. The chemotherapy consisting of Cytarabine and Daunorubicin was initiated immediately after the diagnosis.
Five days after initiation of chemotherapy, she also complained of sudden painless paracentral visual field defect and photopsia in her right eye. Visual acuity was 20/20 in both eyes. Intraocular pressure was within normal limits. Slit lamp biomicroscopy of the anterior segment was unremarkable. Fundus findings revealed multiple hemorrhages with white or pale center (Roth’s spots) around the optic disk and vascular arcades in both eyes. OCT demonstrated hyper-reflectivity of the outer nuclear layer (ONL) and outer plexiform layer (OPL) associated with attenuation of the ellipsoid zone (EZ) nasal to the fovea of the right eye (Fig. ). Outer retina segmentation en-face OCT revealed hyperreflective patch (Fig. ). These findings did not involve the fovea. They were compatible with the diagnosis of AMN.
Nine days after AMN diagnosis, dyspnea, malaise, and cough was gradually initiated. Although the lungs were clear in the CT scan performed at the admission, the CT scan after deterioration of the systemic status of the patient showed multilobar peripheral ground glass haziness and patchy consolidation foci (Fig. ). Based on the positive result of nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and leukopenia (0.5 × 109 /L), the diagnosis of coronavirus disease 2019 (COVID-19) was confirmed. The patient deceased after 6 days because of severe pneumonia.


We report the case of a patient with autism spectrum disorder (ASD) who presented a complex symptomatology and required hospitalization and careful observation to arrive at a correct diagnosis.
A is a 7-year-old boy diagnosed with ASD; he presents low cognitive functioning and moderate level of autistic symptomatology. Previously, genetic investigation (karyotype, CGH-array), metabolic screening, and brain magnetic resonance imaging (MRI) were performed, with negative results. Electroencephalogram (EEG) during sleep showed nonspecific atypia, bilaterally on the central-temporal regions. A attends the first year of primary school with support of a teacher, practices psychomotor, speech, and music therapy. His level of language consisted of simple sentences, used above all for requests. He used some descriptive gesture; pointing was present as request and declarative function. Personal autonomy in the acts of daily life was quite sufficient: he used the bathroom and ate independently. There were frequent stereotyped movements (mannerisms and flickering). Six months before he visits the hospital, he presented a period of behavioral control disorder, with an increase in hyperactivity and agitation in concomitance with the separation of his parents. For this reason, the hours of therapies have been increased, the figures in the rehabilitation setting have been changed, and highly structured behavioral techniques have been introduced (e.g., use of operating conditioning). A showed a progressive loss of verbal and motor skills and loss of previous interests. At the time of admission, A had no initiative, mimicry characterized by a “smiling” facial expression, not congruent to the emotional state, and absence of response to questions and requests. He presented loss of autonomy with the need for continuous assistance (to be fed during meals, exhorted, and helped to go to bathroom). At the neurological examination, focal signs were absent, but A presented a fixed posture and involuntary movements, typically patterned as twisting, involved upper and lower limbs. According to clinical criteria [], these involuntary movements seemed to assume characteristics of dystonic features. Detailing, movement distribution was multifocal, and phenomenology was persistent during the day and not linked to specific triggers; moreover, no others neurological manifestations occurred. At beginning, an isolated dystonia was hypothesized. A complete evaluation was assessed in order to consider possible etiology. The patient underwent blood tests to evaluate the endocrinological, metabolic, coagulative, and autoantibody profile, which result all within normal range. He repeated EEG confirming the result of the previous exam. The ophthalmologic consultation and fundus examination were normal. Neuroradiological examination with brain MRI resulted without significant pathological findings. An organic pathology (metabolic, genetic, or acquired conditions) underlying the disorder was excluded. Considering clinical, instrumental, and anamnestic information, it was hypothesized that the abnormal dystonic movements and postures of the patient might be a phenomenology of a catatonia disorder associated with ASD. Parents refused drug therapy. Treatment was modified with reduction of hours, return of the previous operators, and beginning of a parent training program. In particular, the introduced highly structured behavioral techniques were removed, in favor of a work aimed at supporting the functions of intersubjectivity (i.e., support ludic interest and functional use of objects, improve social playful exchange, and communication functions). Family routines, changed due to parental separation, were resumed. The case was monitored by telephone on a weekly basis. After a month, A showed a slight improvement, involuntary movements were no longer present, the motor picture was more fluid with reduction of fixed posture, and he had started to say a few words. In the following months, he improved gradually, with recovery of skills and autonomy. After four months, the previous level of motor and daily functioning was resumed, confirming that dystonic phenomenology was a manifestation of catatonia.


A 42-year-old man visited our clinic for routine follow-up 1 year after left upper lobe lingular segmentectomy for T1bN0M0 lung adenocarcinoma. He had never smoked and had no medical history. He had no symptoms and physical examination showed no significant findings. Chest computed tomography (CT) showed a newly developed pleural mass on the left hemithorax. The tumor was 34 mm × 25 mm and located in the pleural space (Fig. A). Positron emission tomography (PET) revealed mild 18F-fluorodeoxyglucose uptake with a maximal standardized uptake value (SUVmax) of 2.7 within the tumor (Fig. B). There was no distant metastasis on PET and brain magnetic resonance imaging. The carcinoembryonic antigen value was 2.38 ng/mL, which was similar to the preoperative value.
Given that pleural recurrence of a lung adenocarcinoma was highly suspected, we decided to perform an exploratory thoracotomy. A well-circumscribed ovoid mass was found in the parietal pleura around the fifth intercostal space, which corresponded to the previous thoracotomy site. En bloc resection of the tumor, ribs, and intercostal muscle was performed, followed by chest wall reconstruction. Histopathology showed fibroblastic proliferation appearing as small bundles of spindle cells in abundant fibrous stroma and the spindle cells were positive for vimentin and β-catenin immunohistochemical staining, which was consistent with a desmoid tumor (Fig. ). Next, we performed NGS to confirm the diagnosis and to identify any genetic alterations that might be relevant for the prognosis of this tumor. A missense mutation S45F (serine to phenylalanine substitution at codon 45) of CTNNB1 was detected. Previous studies have reported that the presence of CTNNB1 mutations can be a diagnostic marker for desmoid tumors among spindle-cell tumors, and a specific genotype, S45F mutation, is associated with a high recurrence rate compared to other genotypes.[ Therefore, we were able to confirm the patient's diagnosis and predict the aggressive behavior of this tumor. We decided to perform adjuvant radiotherapy to prevent local recurrence of the tumor. A total of 56 Gy was delivered to the resection bed in 28 fractions during the daily course. There were no postoperative or radiotherapy-related complications during the treatment.
The patient underwent periodic follow-up examinations, including laboratory tests and CT every 3 months, and is currently alive without recurrence of lung cancer as well as a desmoid tumor 38 months after the last surgery.


A male in his 40s with a past medical history of T2DM and hyperlipidemia was diagnosed with COVID-19 three days prior to presentation to the ED. The patient came for the evaluation of worsening symptoms of fatigue, non-productive cough, and poor appetite for six days. He also admitted to several episodes of non-bloody, non-bilious vomiting, and poor oral intake. When questioned, he reported compliance with his home medications including 25 mg of empagliflozin daily, 3 mg of semaglutide daily, 500 mg of metformin twice per day, 40 mg of atorvastatin daily, and 200 mg of modafinil daily. On physical examination, significant findings showed that he was diaphoretic and actively vomiting. His vitals signs were significant for a heart rate of 113 beats per minute, temperature of 37.6 °C (99.7 °F), blood pressure of 122/95 mm Hg, 20 breaths per minute, and 97% oxygen saturation on room air. Comprehensive metabolic panel (CMP) results were notable for a serum sodium level of 133 mEq/L (corrected sodium of 134 mEq/L), carbon dioxide 11 mEq/L, creatinine of 1.5 mg/dL, glucose 177 mg/dL, and calculated anion gap of 25 mEq/L. Complete blood count (CBC) results were significant for a white blood cell count of 11.76 × 103/μL and red blood cell count of 20.4 × 106/μL. Beta-hydroxybutyrate resulted in 8.62 mmol/dL. Venous blood gas (VBG) determined a pH of 7.06, partial pressure of carbon dioxide of 37 mm Hg, partial pressure of oxygen of 31 mm Hg, bicarbonate level of 10.0 mEq/L, and lactate 2.3 mmol/L. Urinalysis was positive for glucose (≥1000 mg/dL) and ketones (>80 mg/dL). Other non-specific laboratory results for active COVID-19 infection revealed a lactate dehydrogenase level of 259 U/L, ferritin 591 ng/mL, creatine kinase 59 U/L, and C-reactive protein level of 94.2 mg/L. His chest x-ray was negative for acute disease (Figure ). Upon initial evaluation in the ED, the patient was administered 2 L of normal saline, 4 mg of intravenous ondansetron, and 20 mg of intravenous famotidine. After laboratory evaluation and diagnosis of eu-DKA, he was started on continuous intravenous (IV) regular insulin at a rate of 1.5 units/hour and a continuous IV infusion of D5 one-half normal saline at a rate of 100 mL/hour. The patient was admitted to the medical ICU for further management of eu-DKA in the setting of active COVID-19 infection. The patient’s hemoglobin A1c was determined to be 10.6% at admission. While in the ICU, the patient was continued on the same regimen of IV insulin and D5 one-half normal saline that was started earlier in the ED. His bicarbonate improved to 22 mEq/L and his anion gap normalized to 10 mEq/L. He was transferred to the general medicine floor after three days, and his regimen was transitioned to 25 units of subcutaneous insulin glargine every night and 10 units of subcutaneous insulin lispro before meals, as recommended by endocrinology. Four days later, he was discharged home in a stable condition and instructed to follow up with endocrinology for his eu-DKA episode and T2DM management. Throughout his entire hospital admission, his COVID-19 respiratory symptoms remained fairly mild.


The patient was a 46-year-old man, 169 cm in height, and weighing 60 kg. He was diagnosed with myotonic dystrophy type 1 5 years previously, with weakness in the distal muscles and electrophysiological tests. The patient complained of vision disability due to cataracts, and phacoemulsification and intraocular lens implantation for both eyes were scheduled under general anesthesia.
Serum creatine phosphokinase level was 2921 U/L (normal range, 43–272 U/L). There were no further abnormal findings on preoperative tests, including an electrocardiogram and transthoracic echocardiogram. Although the relationship between myotonic dystrophy and malignant hyperthermia is controversial, we planned to use total intravenous anesthesia in this case.
The use of propofol, which is a commonly used intravenous anesthetic, might cause prolonged recovery after anesthesia in patients with myotonic dystrophy []. Therefore, we planned to use remimazolam to achieve fast recovery in this case.
No premedication was administered. We administered 6 mg/kg/h of remimazolam intravenously for 1 min. The patient lost the response to the verbal command after the infusion of remimazolam (Fig. ). Continuous infusion of remifentanil (0.2 μg/kg/min) and remimazolam (0.5 mg/kg/h) was started. Neuromuscular monitoring of the left ulnar nerve was commenced using a train-of-four (TOF) stimulus (TOF watch, MSD). Three minutes after administration of 40 mg rocuronium, all four twitch responses disappeared, and tracheal intubation was performed. During surgery, the remimazolam dose was planned to maintain a bispectral index (BIS) value between 40 and 50 with continuous remifentanil infusion (0.1 μg/kg/min). However, the BIS value remained below 40 at a continuous infusion rate of 0.25 mg/kg/h, a 1/4 dose of the standard infusion rate. At this dose, the electroencephalogram showed continuous alpha wave spindles and delta waves (Fig. ). Therefore, we judged that an appropriate anesthesia level was achieved. An additional 5 mg rocuronium was administered 60 min after the first dose because the first twitch response was observed. The surgery time was 46 min, and the infusion of all anesthetics was stopped. At the end of the procedure, TOF showed the first twitch response, and then 180 mg(3 mg/kg) of sugammadex was administered. Three minutes after administering sugammadex, the TOF recovered to 100%. Six minutes after remimazolam discontinuation, the patient opened his eyes on verbal command with sufficient spontaneous respiration. Next, the tracheal tube was removed. Finally, flumazenil (0.2 mg) was administered to boost the recovery, and the postanesthetic course was uneventful. A post-operative interview with the patient was performed on the day and the next day. He had no memory during the surgery.


A 34-year-old-lady, known to have a migraine, presented to the emergency at 31 weeks gestation with a severe right-sided headache for two days. There was preceding continuous, mild headache for two weeks along with photophobia and phonophobia. The headache was partially responsive to paracetamol. She initially took it as her usual migraine, but her pain became severe, mainly involving the forehead and right periorbital region. There was no associated nausea, vomiting, fever or visual complaints. A thorough neurological exam was normal on the day of admission. The patient refused an MRI brain on day one, believing it to be harmful to the fetus. She was kept under observation and prescribed analgesics with an impression of migraine. A day later, her examination revealed partial right ptosis and right sixth nerve palsy with bilaterally reactive pupils and normal fundi. Serum leukocyte count and C-reactive protein were mildly raised. With differential diagnoses of ophthalmoplegic migraine, cerebral venous sinus thrombosis (CVST) or retro-orbital infection, MRI brain without contrast with orbital cuts and MR venogram (MRV) were obtained after counselling the patient. MRI brain revealed almost complete opacification of right frontal, maxillary and bilateral ethmoid sinuses with proptosis of the right eyeball and preorbital soft tissue swelling (Figure ).
There was no evidence of cerebral venous sinus thrombosis. Infectious disease specialist was consulted immediately, and intravenous amphotericin was started with a high suspicion of fungal infection while bacterial coverage was started empirically with meropenem and vancomycin. Amphotericin had to be discontinued after the first dose due to an allergic reaction. Otorhinolaryngology consultation was solicited on day two when she developed proptosis of the right eye along with inflammation of the eyelid and periorbital region. An impression of acute bacterial sinusitis with cellulitis was made. The patient refused for sinus washout. Hence nasal endoscopy was done, and cultures were taken. On day three, the patient’s proptosis and headache worsened. Until then, three consecutive nasal swabs were negative for fungal or bacterial growth, and ongoing blood cultures were also negative. Late at night on day three, the patient had to be rushed to the operating room due to acute development of right-sided facial swelling and an unbearable headache. Right maxillary sinus washout was done that revealed frank pus. Meropenem and vancomycin were continued. Gram stain of pus drained from right maxillary sinus grew gram-positive cocci initially and revealed MRSA finally. Fetal health was unaffected by sinus drainage. The patient improved dramatically after the drainage of pus. Her headache was relieved, and proptosis and ptosis improved. On day five, she was discharged home with advice to continue intravenous antibiotics. On a follow-up one week after discharge, the patient had complete recovery without any complications.


A 46-year-old female presented to us with multiple episodes of increased hunger, diaphoresis, palpitations, tremors, anxiety, and dizziness for the last eight months. These episodes usually occurred in the fasting state. During one such episode, her blood glucose recorded by glucometer was 35 mg/dl. Her symptoms were reversed by intake of carbohydrate diet. Though Whipple’s triad was not established as plasma glucose was not measured, the symptomatology did merit for further evaluation []. She had no history of diabetes, chronic liver disease, chronic kidney disease, or history of intake of any drug known to cause hypoglycemia.
On further probing, she revealed history of recurrent renal stones for the past 16 years. In addition, she had history of galactorrhea and oligomenorrhea for the past two years. Apart from this, there was no other significant history. She was the index case in her family. However, her family history did reveal that she was part of a large kindred. She had five siblings and 22 step siblings from the five marriages of her father. Patient’s father who had similar episodes of neuroglycopenic symptoms [suspected (?) insulinoma] and history of renal stones (Figure ) had expired before evaluation. There was history suggestive of at least one MEN1-associated endocrine tumor among eight of her siblings. The pedigree chart is shown in Figure .
After admission in our ward, the patient had an episode of spontaneous hypoglycemia, and critical sample was analyzed that revealed non-ketotic hyperinsulinemic hypoglycemia (blood glucose of 40 mg/dl with corresponding serum insulin 19.4 µU/ml and C peptide of 4.9 ng/ml, blood ketones of 0.1 mmol/L) []. Serum insulin and C peptide were measured by electrochemiluminescence (ECLIA) assay (Cobas e411, Roche diagnostics, Germany), while blood ketones were measured on a finger prick test using a point of care device (normal range 0.4-0.5 mmol/L). Patient also had parathyroid hormone (PTH)-dependent hypercalcemia with hypercalciuria [serum total calcium 12.3 mg/dl (normal range: 8.5-10.5 mg/dl), serum intact PTH of 210 pg/ml (normal range 15-65 pg/ml), 24-hour urinary calcium of 450 mg/day (normal range < 250 mg/day)]. Serum calcium was measured on Roche Hitachi 917 (automated analyzer), while serum intact PTH was measured on ECLIA (minimum detection limit 1.5 pg/ml). Her serum prolactin level, measured by ECLIA, was also elevated, 92.6 ng/ml (normal range, 10-29 ng/ml). Other pituitary hormones were within normal limits.
A suspicion of MEN1 syndrome was made, which was later confirmed by positive screening test for MEN1 gene mutation (Deletion: c.824-832delGGTACCCCA in exon 5 of MEN1 gene on whole gene sequencing).
For evaluation of PTH-dependent hypercalcemia, she underwent technetium-99m SESTAMIBI scan that revealed involvement of three parathyroid glands (left superior, left inferior, and right paratracheal) (Figures , ). However, the four-dimensional computed tomography (4D CT) (Figure ) and four-dimensional magnetic resonance imaging (4D MRI) (Figure ) showed involvement of all the four glands.
For evaluation of hyperinsulinemic hypoglycemia, she underwent multiphase contrast-enhanced computed tomography (CT) of abdomen that revealed two mass lesions in the pancreatic head and tail, respectively (Figures , ).
Patient also underwent Ga-68-DOTANOC positron emission tomography (PET)/computed tomography (CT) that revealed somatostatin receptor (SSTR) expressing lesions in the head of the pancreas (1.6 cm x 1.5 cm) and tail of the pancreas (3.2 cm x 2.2 cm) (Figures -). She also underwent endoscopic ultrasonography (EUS) that revealed multiple hypoechoic round lesions in the pancreas (max: 3.5 cm x 2.1 cm x 0.8 cm) with vascularity in the lesions, two lesions of diameter 2.1 cm and 1.1 cm in the body of pancreas, and four small lesions in the tail of pancreas (~8 mm each).
For evaluation of pituitary disease, she underwent an MRI sella that revealed a 9-mm pituitary adenoma (Figures , ).
She underwent removal of all parathyroid glands, cervical thymectomy, and auto-transplantation of normal parathyroid tissue into left forearm. Postoperatively, she was managed with calcium supplements and calcitriol. She also underwent total pancreatico-duodenectomy along with splenectomy. Post-surgery, glycemic control was achieved with insulin. Exocrine functions were managed with pancreatic enzyme supplements. For prolactinoma, she was started on tablet cabergoline 0.5 mg twice a week.
Histopathology of parathyroid specimens revealed parathyroid hyperplasia, while that of pancreatic specimen revealed well-differentiated neuroendocrine neoplasm, grade 1 (G1), with multiple multicentric microadenomas (pathological stage: pT2N0). Patient was counseled regarding the importance of regular follow-up. Investigations and their intervals were planned as defined for MEN1 patients [].
Her brother, who was a 42-year-old male, also had symptoms suggestive of spontaneous hypoglycemia corrected by intake of carbohydrate diet and acromegaloid habitus. He too was admitted for evaluation and was found to have acromegaly with pituitary macroadenoma, primary hyperparathyroidism with adenomas in all the four parathyroid glands, and hyperinsulinemic hypoglycemia with multiple insulinomas. He too underwent total parathyroidectomy along with auto-transplantation of normal parathyroid tissue in non-dominant forearm, with cervical thymectomy. For pituitary macroadenoma, he underwent trans-nasal trans-sphenoidal surgery (TNTS) with uneventful recovery. However, he refused to undergo pancreatic surgery and instead resorted to medical therapy with frequent, low carbohydrate meals.


A 73-year-old man was diagnosed with colon cancer and underwent right hemicolectomy at our hospital. The final diagnosis of colon cancer revealed adenocarcinoma, type 2, 70 × 40 mm, tub2 > tub1, T4a (SE), int, INFb, Ly1a, V1b, Pn0, N1a (1/30), p-stage IIIB (according to the ninth edition of TNM classification). Computed tomography (CT) before surgery for colon cancer revealed a solid nodule measuring 16 mm in diameter in the laterobasal segment (S9) of the right lung (Fig. a). Three months after the surgery for colon cancer, the size of the pulmonary nodule increased (diameter, 18 mm; Fig. b). The levels of tumor markers, including carcinoembryonic antigen (1.7 ng/mL), carbohydrate antigen 19-9 (5.2 U/mL), cytokeratin 19 fragment (2.2 ng/mL), and pro-gastrin-releasing peptide (66.9 pg/mL), were all within normal levels. The pulmonary tumor was highly suspected to be a metastasis from the colon cancer because of the tumor growth. No other metastases were observed on contrast-enhanced CT. We considered preoperative bronchoscopy. However, the patient preferred surgery for diagnostic and therapeutic purposes. Preoperative three-dimensional CT (3D-CT) angiography revealed that A7a branched from the right main PA, whereas A7b branched from the A8+9+10 as usual (Fig. a, b). The A7a and A7b were located on the ventral and dorsal sides of the basal vein, respectively.
Right basal segmentectomy was performed via video-assisted thoracic surgery. The interlobar fissure between the middle and lower lobes was incomplete. Then, we dissected around the inferior pulmonary vein (IPV) to identify the border of the middle and lower lobes. Subsequently, during dissection of the cranial side of V6, we found the A7a that was close to V6 (Fig. a). The A7a branching from the right main PA was observed behind the V4+5 and middle lobe bronchus during surgery (Fig. b). The basal PA except for A7a was divided using a stapler, and A7a was ligated and divided (Fig. c). Then, the basal bronchus was divided using the stapler. After the vein of the basal segment (V7–10) was divided, the intersegmental plane was dissected using the stapler along the inflation and deflation lines. Intraoperative frozen section diagnosis revealed that the tumor was compatible with a metastasis from the colon cancer. The total operation time was 144 min, and the total blood loss volume was 30 mL.
The postoperative course was uneventful. The tumor had reached a maximum diameter of 20 mm, and the final pathologic diagnosis was combined small cell carcinoma and adenocarcinoma as opposed to the frozen section diagnosis. The pathological staging of the tumor was p-T1cN0M0, p-stage IA3. Although we proposed completion right lower lobectomy with systemic mediastinal lymph node dissection, the patient did not agree. The patient received adjuvant chemotherapy (XELOX) for colon cancer after a discussion with the cancer board in our institution. There was no recurrence of lung and colon cancer at a 1-year follow-up.


A 36-year-old male was otherwise healthy except for undergoing one session of ESWL for kidney stones 24 months ago. Kidney function (represented as serum creatinine) was normal. Twenty-four months later, he presented with fever, cough, and hemoptysis for 5 days. He was anemic with hemoglobin 75 g/L and serum creatinine was 691 μmol/L (eGFR, 8 mL/min/1.73m2). Two days later, he developed gross hematuria and serum creatinine rose to 884 μmol/L (eGFR, 6 mL/min/1.73m2), at which time he was referred to our hospital. He was a long-term cigarette smoker and had gasoline exposure 15 days ago.
On admission, he was pale and febrile with no lymphadenopathy. Breath sounds were weak in both lungs on auscultation. Serum creatinine rapidly increased to 1279 μmol/L (eGFR, 4 mL/min/1.73m2) with oliguria and hemoglobin decreased to 49 g/L. Chest radiography suggested bilateral pulmonary hemorrhage. The circulating anti-GBM antibody was positive, with the titer >200 RU/mL (Euroimmune ELISA kit, normal range <20 RU/mL), while the serum anti-neutrophil cytoplasmic antibody (ANCA) was undetected ().
Anti-GBM disease was diagnosed based on the renal-pulmonary involvement and positive serum anti-GBM antibody. The patient was prompted to plasma exchange, intravenous methylprednisolone pulse treatment, cyclophosphamide, and hemodialysis. After 17 sessions of plasma exchange, he became afebrile without hemoptysis. His serum anti-GBM antibody decreased to 33 RU/ml and serum creatine to 425 μmol/L (eGFR, 14 mL/min/1.73m2). Repeated chest radiography indicated the absorption of his hemorrhage. He was dialysis-independent on discharge and a 3-month follow-up.
Sera from this patient were tested for antigen spectrum using recombinant human α1–5(IV)NC1 chains and chimeric proteins containing epitopes EA and EB on α3(IV)NC1 (). The patient's serum recognized α1 and α3(IV)NC1 domains, and both epitopes EA and EB of α3(IV)NC1. The immunoglobulin G (IgG) subclass distribution against α3(IV)NC1 was also tested for the sera. All 4 subclasses of IgG were detected, with the dominance of IgG2 and IgG4 (; ).


A 50-year-old male undertook one session of ESWL for ureter stones with normal kidney function 22 months ago. He was a 20-year cigarette smoker but had quit smoking for 10 years. Twenty-two months later he was referred to our hospital for fever, gross hematuria, and rapidly progressive renal dysfunction. He had suffered from intermittent fever for 2 months without other indicating symptoms and it could not be resolved by antibiotics. Fifteen days prior to admission, he developed gross hematuria and the serum creatinine progressed from 160 μmol/L (eGFR, 40 mL/min/1.73m2) to 504 μmol/L (eGFR, 11 mL/min/1.73m2). No stones were found by renal ultrasound.
After admission, he was diagnosed with anti-GBM disease due to positive serum anti-GBM antibody (183 RU/mL). His serum ANCA was tested negative. He received 7 sessions of plasma exchange, intravenous methylprednisolone pulse treatment, and hemodialysis. His condition improved and hematuria disappeared afterward. Serum creatinine decreased to 353 μmol/L (eGFR, 16 mL/min/1.73m2) and anti-GBM antibody titer to 51 RU/mL on discharge. The patient was dialysis-dependent during a 60-month follow-up ().
The patient's sera reacted with all five α chains and both EA and EB epitopes of α3(IV)NC1. All 4 IgG subclasses to α3(IV)NC1 were detected with the dominance of IgG2 (; ).


A 74-year-old female received one session of ESWL for kidney stones 10 months ago when the renal function was normal. Ten months after ESWL, she complained of fever and gross hematuria with urinary irritation symptoms for 2 weeks. No leukocytosis was found, but her urinalysis revealed white and red blood cells. Initial workups showed elevated C-reactive protein (96 mg/L) and normal serum creatinine (87 μmol/L; eGFR, 55 mL/min/1.73m2). Renal ultrasound showed no stones. She was diagnosed with urinary tract infection and treated by intravenous antibiotics, after which she reported no symptom improvement but developed oliguria and bilateral edema of lower extremities. Her serum creatinine deteriorated to 1066 μmol/L (eGFR, 3 mL/min/1.73m2) within 9 days. Then she was referred to our hospital.
On admission, physical examination revealed a sick and pale woman with no rales on auscultation. Serum anti-GBM antibody was positive (196 RU/mL) while the serum ANCA was not. Renal biopsy revealed severe necrosis of glomerular capillary walls and cellular/cellular-fibrous crescents in all 32 glomeruli on light microscopy (), with no electron-dense deposits on electron microscopy. The immunofluorescence microscopy was negative on a sclerotic glomerulus. She was treated by methylprednisolone pulse and cyclophosphamide. Plasma exchange was not performed, given the poor prognosis based on renal biopsy. Her renal function did not recover and she remained dialysis-dependent. The patient died of esophagus cancer 2 years after discharge.
The patient's sera recognized all five α chains and both EA and EB epitopes of α3(IV)NC1. As for circulating IgG to α3(IV)NC1, all four subclasses were detected with the dominance of IgG2 (; ).


The patient was a four-month-old boy from first-degree consanguineous marriage (). He presented by the age of two months chronic diarrhea, recurrent respiratory tract infections, oral thrush, locoregional BCGitis, and failure to thrive. The laboratory workup showed a profound lymphopenia and an absent thymus shadow in the chest X-ray. A diagnosis of SCID was suspected, and an immunological workup was done ().
Therefore, the diagnosis of a SCID was established. He was on antituberculosis to treat the BCGitis (rifampicine, isonhiazid, and ethambutol) and antifungal (fluconazole). He received also trimethoprim-sulfamethoxazole as a prophylaxis and immunoglobulin replacement every three weeks. Each infectious episode was treated actively. Due to a lack of hematopoietic stem cell transplantation, he died by the age of 1 year and a half.


A 35-year-old Bangladeshi man presented to the emergency department at Hamad Medical Corporation, Doha, Qatar, with two-day history of progressive right lower abdominal pain, associated with four times vomiting and loss of appetite. He was doing completely well but developed these symptoms few hours after a strong direct camel kick on his right abdomen. He did not have any urological symptoms, nor any comorbidities, and his systemic review was unremarkable.
The patient was conscious and had normal vital signs. Generally, was looking well, abdominal examination showed a right lower abdominal bruise, tenderness, rebound tenderness, and involuntary guarding in the right iliac fossa. Head to toe examination showed no other signs of trauma. Laboratory tests showed high inflammatory markers (white blood cell count (WBC) 15.5 K/μL, hemoglobin 15.3 g/dL, platelets 207 K/μL, CRP: 90.5, and bilirubin: 29.1). CT abdomen with IV and oral contrast was done and showed a dilated appendix in the right iliac fossa (16 mm in diameter), with wall enhancement and periappendiceal fat stranding (). The patient was diagnosed with acute appendicitis, and an emergency laparoscopic appendectomy was performed. Intraoperative findings showed grossly inflamed appendix with fibrinous exudate with no collection or perforation (), and the inspected other intra-abdominal solid and hollow organs were normal. Postoperatively, the patient recovered well and was discharged one day after surgery. On follow-up 2 weeks in the clinic, he was completely healthy, wounds were healed, and histopathology confirmed the diagnosis of acute appendicitis.


A 61-year-old man presented to the ENT outpatient department with a history of a right tonsillar mass for 1 month. There was no history of throat pain, fever, or weight loss. The other medical and family histories were not significant.
On physical examination, there was a 3 × 2 cm, nontender, mobile mass arising from the right lateral wall of the oropharynx (). Few palpable lymph nodes were present at right levels III and IV. Hematological investigation revealed mild eosinophilia (9%). Contrast-enhanced computerized tomography (CT) scan of the neck revealed well-defined minimally enhancing isodense soft tissue mass (31 × 27 mm) in the oropharynx on the right side (). Fine needle aspiration cytology (FNAC) from cervical lymph nodes revealed reactive lymphadenitis. The patient underwent R0 resection of the oropharyngeal mass. Postoperative period was uneventful.
Histopathological examination of the specimen showed multiple lymphoid follicles with germinal centers and eosinophilic infiltration (Figures and ). The vascular component consisted of hyalinized blood vessels lined by flat endothelial cells (). The findings were suggestive of Kimura's disease. The patient was advised for immunohistochemistry (IHC) to confirm the diagnosis. On IHC, the cells were positive for CD3, CD5, CD20, CD23, and CD45. Germinal center cells were positive for CD10, and BCL2 was positive in mantle zone cells and paracortical areas. A serum IgE level was measured, which was elevated at 276 kU/L (normal: 0–75 kU/L), which further supported the diagnosis of Kimura's disease. Final diagnosis of Kimura's disease was made based on these findings.


We received a 26-day-old male newborn who was referred from a regional hospital for multiple fractures and limb deformities discovered at birth. He was born at 39 weeks through vaginal route with breech presentation and a birth weight of 2700 g. It was an uneventful twin pregnancy. Antenatal laboratory tests were normal. Three ultrasounds were done during prenatal period with no reported abnormalities. There was no consanguinity, no family history of short stature. Limb deformity was found in a 6-year-old cousin but the underlying cause was unclear (Figure ). The twin sister was in good health at birth.
At clinical presentation, anthropometric parameters included a weight of 3200 g (−1 SDS), height 47 cm (−2 SDS), and head circumference of 35 cm (+ 0.5 SDS). The child presented with reduced mobility, frontal bossing, white sclerae, moderate respiratory distress, bowed legs, and shortened limbs (Figure ). Limbs X-rays showed multiple diaphyseal fractures of long bones, demineralization, and curved bones (Figure ). Transfontanellar brain ultrasound and cardiac ultrasound were normal. Laboratory findings included normal calcium (97.2 mg/L) and increased alkaline phosphatases (374.68 IU/L). Genetic tests are not yet available in our country. According to clinical and radiographic findings, Osteogenesis Imperfecta was the more likely diagnosis of this bone fragility. We suggested OI type III as diagnosis due to early presentation. For management of this condition, the child received orthopedic treatment for recent fractures and oral Vitamin D supplements. The child is currently 9 months old with a weight of 7750 g (−1 SDS), a height of 57 cm (- 3.5 SDS), and a head circumference of 44 cm. He recently received the first dose of bisphosphonates. A recent lumbar spine X-ray revealed tiered vertebral collapse from T12 to L3 with no spinal deformities. The physiotherapist tried to maintain a semi-sitting position to avoid spinal deformities.


We received a 37-day-old male baby who was referred by a surgeon for medical management of multiple fractures and limb deformities discovered at birth. It was an eventful pregnancy with normal prenatal tests. A 3rd trimester ultrasound revealed femoral bowing and shortening. He was delivered through cesarean section at 37 weeks due to uterine scar from a 32-year-old mother. He had a birth weight of 3000 g and a height of 40 cm. At birth, he presented with limb deformities and painful mobility of lower limbs. He was admitted for an early neonatal sepsis at day 2 of life with good improvement. He is the second child of the family with no family history of consanguinity nor limb deformities.
At clinical presentation, anthropometric measurements included a weight of 4000 g (−1 SDS), height of 45 cm (−2 SDS), and head circumference of 35 cm (+0.5 SDS). The child presented with reduced mobility, frontal bossing, blue sclerae, bowed legs, and shortened limbs. Radiography of the limbs showed multiple diaphyseal fractures of long bones and curved bones (Figure ). The patient also presented with an undisplaced sternal fracture. Genetic tests are not yet available in our country. According to clinical and radiographic findings, Osteogenesis Imperfecta was the more likely diagnosis of this bone fragility. We suggested OI type II or III as diagnosis due to antenatal deformities and multiple fractures at birth. For management of this condition, the child received orthopedic treatment with several casts for recent fractures. Bone callous was formed after 8 weeks with pain improvement. He also received oral Vitamin D supplements. Bisphosphonates are planned but not yet available.


A 67-year-old Japanese man presented to the emergency department with fever and a constant headache that began 5 and 9 hours ago, respectively. The location of the headache was at the back of his head. He described the pain as pulsating and rated it 10 on a 0 to 10-point Numerical Rating Scale. He had no gastrointestinal (GI) symptoms such as nausea, vomiting, or diarrhea. He had a past medical history of hyperlipidemia and type 2 diabetes that was well controlled by sitagliptin alone; his hemoglobin A1c level was 6.1%. He drank 2-3 glasses of Shochu (alcoholic beverage) every day; however, his previous liver function tests were normal. Therefore, we considered him to be immunocompetent.
His blood pressure, pulse rate, respiratory rate, and body temperature were 123/78 mm Hg, 110/min, 18/min, and 39.1°C, respectively. He was alert and oriented. Physical examination did not reveal any abnormalities. Meningeal irritation symptoms were negative. We performed blood tests, urine analysis, chest X-ray, computed tomography (CT) scan of the head, and lumbar puncture to find the source of the fever and rule out meningitis. Laboratory tests revealed normal findings (white blood cell count, 8.3 × 109/L; hemoglobin, 144 g/L; platelets, 169 × 109/L; creatinine, 0.65 mg/dL; blood glucose, 117 mg/dL), although mild elevation of CRP levels was observed (2.5 mg/dL: normal range 0.0-0.3 mg/dL). Lumbar puncture and other tests were also normal (appearance, clear; no xanthochromy; cell counts 1/µL [monocyte]; glucose, 80 mg/dL). Although the diagnosis and the source of fever were unclear, he was admitted to our hospital for observation for headache. Blood culture was done. We treated him with drip infusion and did not start antibiotics as our initial diagnosis was a viral infection and there were no signs of a severe bacterial infection. We planned to start antibiotics if the results of the blood culture came back positive.
Six hours after hospital admission, he began having frequent vomiting and diarrhea episodes. We continued to observe him as his vital signs remained normal. Eleven hours later, he became agitated and his consciousness deteriorated. His oxygen saturation level decreased and petechia appeared on his upper and lower limbs. He was re-evaluated with blood tests and contrast-enhanced CT scan for chest, abdomen, and pelvis. His blood tests showed signs of disseminated intravascular coagulopathy (DIC) and multiorgan failure (MOF): pancytopenia (white blood cell count, 0.6 × 109/L; hemoglobin, 97 g/L; platelets, 12 × 109/L), renal dysfunction (BUN, 25 mg/dL; creatinine, 2.52 mg/dL), elevated aminotransferase (AST, 386 IU/L; ALT, 90 IU/L), and coagulopathy (PT-INR, 3.15; D-dimer, 55.4 mcg/mL; APTT > 180 seconds). The CT failed to demonstrate any possible source of infection and his spleen appeared to be normal with no signs of hypoplasia. Even though the origin was unclear, fulminant sepsis was apparent; we transferred the patient to a tertiary hospital nearby for ICU care. At this time, further history taking revealed that the patient had been bitten by his dog 7 days before admission, although we were unable to find any wounds or scar even after careful physical re-examination after learning of this history. Subsequently, we considered severe infection due to an animal bite, such as C canimorsus or Pasteurella multocida infection, as the differential diagnosis.
After transfer, he was admitted to the ICU. He became hypotensive and was given a bolus of normal saline and started on noradrenaline. He was also given broad-spectrum antibiotics (levofloxacin 500 mg and meropenem 1 g). He was intubated due to respiratory failure. Just after admission, we received a report that his blood smear (Giemsa staining) showed the presence of bacteria in leukocytes (Figure ). In spite of intensive care, he remained hypotensive and suffered from complications of GI bleeding. After 41 hours of presentation, the patient died as a result of DIC and MOF. The day following the patient's death, blood cultures tested positive for bacteremia; 28 days after his death, the bacteria were identified as C canimorsus using 16S rRNA gene sequence analysis.


A five-month-old girl was brought to the emergency room with a history of falling in the shower one week before and development of somnolence three days later. Previous history examination showed that the patient was born with a diffuse brain lesion of no defined etiology, and computed tomography (CT) of the brain at two months showed a compromised brain and compensatory enlargement of lateral ventricles associated with a thin cortical mantle (Figure ).
However, the patient grew with no head measurement abnormalities, and the fontanelles present were small.
At admission, after the fall and head trauma, she presented with somnolence, a Glasgow Coma Scale score of 10, sustained bradycardia (70 bpm) without hypertension, and hypothermia (33°C). The oxygen saturation was 98% at ambient air supply, and no bruises were noted in the physical examination.
The patient underwent CT and MRI of the brain, which showed a massive bilateral subdural hematoma with two hyperdense masses adherent to the collapsed brain (Figures -).
The non-accidental head trauma was ruled out after psychological assessment and the following measures. An ophthalmologist performed fundoscopy and observed not retinal abnormalities such as hemorrhage. In addition, the patient showed good nutrition conditions, and radiographs of her long bones showed no fractures, even in other periods.
Because of the massive fluid collection in the subdural space, we decided to perform neurosurgical intervention using neuroendoscopy, expecting to have better navigation in this case. Under general anesthesia, the patient was positioned in the supine position, with the head in a neutral position in a horseshoe headrest. A unique burr hole was made in the frontal region (Video ).
After durotomy, we drained the hypertensive and turbid fluid. Next, we introduced a peel-away sheet into the subdural space and inserted a rigid neuroendoscope with a zero-degree optic. After irrigation of the right subdural space, the hematoma was identified adherent to the arachnoid surface, which also presented a laceration. The falx cerebri presented with natural holes. After enlargement, the contralateral hemorrhage was drained. At the end of the procedure, we observed the entire middle fossa and the anterior fossa with ethmoidal arteries (Video). No drains were introduced. There was an immediate improvement of the heart rate and the level of consciousness. The patient received the discharge from the hospital after one week after the procedure. No complications were observed.
MRI obtained 30 days after the procedure showed brain expansion with a thin cortical mantle (Figure ).


An 18-year-old male patient presented with a history of mass and pain in the thigh. After the imaging, a biopsy was taken confirming the final diagnosis of a high-grade chondroblastic/osteoblastic osteosarcoma of the distal femur stage IIB (Figure ).
The patient received neoadjuvant chemotherapy with MAP (methotrexate, doxorubicin, and cisplatinum), and limb salvage surgery was subsequently performed in October 2000. For the reconstruction, an osteochondral allograft fixed with a rigid stainless steel plate was selected. In the postoperative period, the extremity was immobilized with an articulated brace until some signs of union in the imaging were observed. The patient successfully completed the adjuvant chemotherapy course without evidence of recurrence or metastasis. The allograft unfortunately progressed to non-union, and after one year of the fixation (November 2001) a fracture in the plate was identified. The case was discussed and the decision was to revise the osteosynthesis. In the subsequent follow-up, weight-bearing was restricted until consolidation was achieved. During the rehabilitation process, an articulated brace in the knee was prescribed, with the association of progressive gain in quadriceps strength.
One year after the last surgery (November 2002), the dislocation of the extensor mechanism and posteromedial femorotibial subluxation was identified. The range of movement at this time was acceptable (10° to 90°), and the pain was manageable; therefore, no further intervention was performed until January 2004, when the patient presented with pain. At this time, several osteoarthritic changes were observed, and for that reason the knee joint was replaced with a constrained revision implant. The results were satisfactory with early recovery in the range of movement (0°-100°), without leg length discrepancy and adequate strength to achieve gait without external aids. In November 2006 (two years after the last intervention), the patient presented to the clinic with sudden loss in the range of movement and with pain. New imaging identified a supracondylar fracture in the allograft, with the subsequent failure of the knee implant (Figure ).
After considering the options available, the therapeutic decision was to perform a revision with a new APC, as it was felt that an endoprosthetic replacement would lead to important bone loss. The patient had the new intervention in February 2007, in which the fractured allograft was removed and a new massive bone allograft was placed. The reconstruction was stabilized with a revision prosthesis with a long femoral stem (28 cm) and a 12-hole plate with cables (Figure ).
The clinical progression was adequate, with a recovery of the movement and a decrease in the preoperative pain levels. During the follow-up, the integration of the bone graft was observed, with the maintenance of appropriate alignment and relationship between the prosthesis, the bone allograft, and the native bone (Figures , ).
At present, the patient is 36 years old and has been followed for 10 years since the last intervention. He is able to walk without any external aids, with no leg length discrepancy. He can perform full extension of the knee and flexion up to 90° (Figure ).
At the last visit to the clinic, no further surgical interventions have been required.


A 49-year-old male addicted to intravenous drug abuse, presented with severe pain abdomen, abdomen distension, constipation and bilious vomiting for four days. On examination, abdomen revealed a peritonitis sign and was having tachypnea and tachycardia and blood pressure was 90/60 mmHg. Blood parameters showed leucocytosis with TLC- 24,000 cubic millimeters, ABG showed mild metabolic acidosis pH being 7.23, and renal and liver profile was normal, blood culture was sterile. Anti-hepatitis C virus (HCV) enzyme-linked immunosorbent assay (ELISA) was positive. Erect X-ray of the abdomen showed air under the diaphragm. He was resuscitated and with the diagnosis of perforation peritonitis underwent exploratory laparotomy, intra-operative findings revealed around 1 litre biliopurulent free fluid in the peritoneum along with ileal perforation of size approx. 1 x 1 cm which was proximal to the stricture segment of the ileal loop (Figure. ), multiple pus flakes were present over the bowel. We did resection of the perforated ileal segment and did double barrel ileostomy. Postoperatively patient did well, oral intake was started by day 2, and was discharged by day 6. On follow-up, anti-HCV drugs were started due to raised HCV-RNA viral load. He also underwent deaddiction therapy for intravenous addiction. Surprisingly histopathology report came out as transmural necrotizing inflammation with multiple suppurative granulomas. These granulomas showed many negative shadows (Figure and B) in hematoxylin eosin-stained sections. Methenamine silver nitrate staining was carried out to identify the negative shadows and showed many easily foldable friable fungal profiles with right-angled branching (Figure and D) conforming to the morphology of mucormycosis. He did not receive anti-fungal medication as he was discharged earlier than the pathology report and was doing well in follow up. At five-month follow-up on anti-HCV therapy with no intravenous addiction and planned for restoration of bowel continuity.


A 57-year-old woman had received infliximab for psoriatic arthritis for 5 years. She was admitted to our hospital with a complaint of right nasal obstruction for 1 month. A granulomatous mass with an irregular surface was found in the anterior right nasal cavity (). A computed tomography scan revealed a tumor shadow localized in front of the right nasal cavity (). A tissue sample was obtained with nasal forceps, and histological examination showed granulation tissue. Application of steroid ointment did not reduce the size of the tumor, and therefore, the tumor was resected under local anesthesia 6 months after the first visit. The tumor was attached to the anterior nasal septum, and after excision, the base was cauterized. Pathological examination revealed an epithelioid granuloma with multinucleated giant cells. Ziehl–Neelsen staining was negative. The tumor recurred 3 months after resection. IGRA (T-SPOT.TB test) was positive, and we performed tissue culture for mycobacteria because of suspected nasal tuberculosis. The smear microscopy was grade 1, and the polymer chain reaction tests for tuberculosis and Mycobacterium avium complex were negative. Individual orange-yellow colonies developed after 8 weeks of incubation on liquid (MGIT) media at 37°C and after 3 weeks of incubation on 2% Ogawa egg medium at 30°C. M. marinum was identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The lesion disappeared 2 months after administration of oral minocycline (4 weeks, 100 mg twice daily) followed by oral clarithromycin (4 weeks, 200 mg twice daily) and discontinuation of infliximab (). After the clinical diagnosis was confirmed, a detailed life history was taken. The life history revealed that she has many tropical fish and sometimes uses her bare hands to clean fish tanks.
The patient provided written consent for the use of her clinical details in this case report. The study was conducted in accordance with the Declaration of Helsinki (1964).


A 70-year-old man presented to our hospital with complaint of right thigh pain. A computed tomography (CT) scan revealed a hematoma in the right thigh. We recommended hospitalization, but the patient wanted outpatient treatment with tranexamic acid because he had received the same treatment earlier for this condition. He received hemostatic infusion for three consecutive days in the outpatient clinic, and hemoglobin level of 13.2 g/dl from one month ago dropped to 11.3 g/dl on the day of injury and to 7.9 g/dl two days after the injury. However, there was no further progression of anemia and the pain decreased. Therefore, the infusion was stopped on the fourth day.
When we looked at the past medical records, he had presented to our hospital with the principal complaint of persistent subcutaneous hemorrhage at the age of 54 years. He had an abnormal prothrombin time (PT) % of 21.0% and activated partial thromboplastin time (aPTT) of 99.4 seconds. Consequently, he was referred to two university hospitals but no specific cause could be found. The doctor at the hospital had said, “factor VIII 4.7% and factor IX 0.6% suggest a broad spectrum of coagulation factor abnormalities. Although he had positive lupus anticoagulant (LAC), the diagnosis of antiphospholipid antibody syndrome could not be made. We cannot make a diagnosis, but FFP improves the coagulation activity to some extent, so use it in the event of bleeding.” Subsequently, there were numerous recurrent bleeding events, with major bleeding occurring every two years, such as in the ilium, pelvic cavity, subdural, iliopsoas, brachial muscles, and mediastinum (). However, many of these bleeds healed spontaneously within a few days with conservative treatment. For this reason, the patient was given the provisional diagnosis of “circulating anticoagulant factor disorder” at the outpatient clinic of our hospital. Considering the age of the patient, the possibility of additional serious bleeding events was high, and therefore, we decided to examine the patient again.
He had never undergone a gastroscopy or surgery until the age of 54. He had no history of chronic diseases, such as allergic diseases and collagen diseases. His only regular medication was tranexamic acid. There was no subcutaneous hemorrhaging on physical examination. Blood tests showed a prolonged PT-INR of 4.5, along with aPTT of 99.6 seconds (). As reported 16 years ago, coagulation activities of factor V, VII, VIII, IX, X, XI, XII, and XIII were all reduced (1–26.5%). In addition, lupus anticoagulant (diluted Russell snake venom time method) and cardiolipin antibodies were positive, as were anti-factor VIII and IX antibodies by the Bethesda method.
Both PT-INR and aPTT were prolonged, which led us to suspect diseases such as disseminated intravascular coagulation (DIC), liver failure, antiphospholipid antibody syndrome, vitamin K deficiency (including due to warfarin), and drugs (heparin, argatroban, and DOAC). However, platelet count, Fib, and proteins induced by vitamin K antagonism (PIVKA) test were within the normal range, and the disease course did not fit these diagnoses.
Therefore, we suspected a deficiency of coagulation factor II, V, and X which are common to the coagulation pathways evaluated by PT and aPTT. We first performed the hepaplastin test (HPT) and thrombotest (TT) to investigate whether the coagulation tests changed with factor V (FV) supplementation (). The TT value was 3.7%, while the TT value calculated from PT-INR was 21% []. We determined that the patient was FV deficient because of the difference in TT induced by a high-dose of bovine FV supplementation.
Next, we performed a cross-mixing test to determine whether FV deficiency was congenital or acquired. The results showed an immediate type of inhibitory pattern (). Incubation at 37°C for 2 hours is required for anti-factor VIII antibody because of its weak inhibitory effect, whereas anti-FV antibody has a strong binding power and does not require incubation. This case also showed an immediate inhibitory response, suggesting the presence of anti-FV antibodies.
Since anti-FV antibody measurement is a laboratory-level test, we asked other institutions to measure them. As expected, both an immunoblot assay and enzyme-linked immunosorbent assay (ELISA) using purified human plasma FV confirmed the presence of anti-FV autoantibodies [] and he was diagnosed with autoimmune FV deficiency. The plan is to treat him with immunosuppressive drugs in the future.


A 36-year-old male patient presented at metabolic bone disease clinic at the Aga Khan University Hospital with history of multiple fragility fractures and juvenile osteoporosis since childhood. There was no history of neurological or cardiovascular complications nor any urinary symptoms.
Upon physical examination, the patient's height was 159 cm and weight was 95 kg. He displayed a prominent forehead, hypertelorism, long eyelashes, and micrognathia. Furthermore, his hands were short and stubby with acroosteolysis and broad dark nails. There were no signs of local inflammation in either fingers or toes. He had lost all his teeth and had replaced them with dentures. The liver and spleen were not palpable and no abnormalities were noted on cardiovascular and neurological exams. Previous consultations in the United States of America, during his childhood had considered the possibility of HCS due to the presence of acroosteolysis. He had been taking bisphosphonates including Pamidronate and Zoledronic Acid since childhood. He was on Prolia when he presented this time.
shows the results of bone biochemistry and Dual-energy X-ray absorptiometry (DXA) findings at an interval of two years. Complete blood count, serum electrolytes, liver and renal function tests (except gamma-GT, which was marginally raised) were within the normal range on different occasions. In addition, thyroid profile, follicle stimulating hormone, and luteinizing hormone & free androgen index were also within the reference intervals.
Based on history & facial dysmorphism, he was referred for geneticist consult. DNA sequence analysis of the NOTCH2 coding sequence was performed on genomic DNA extracted from peripheral leucocytes at the Invitae Corporation, San Francisco CA 94103. A pathogenic variant in NOTCH2, Exon 34, c.6426_6427insTT (p.Glu2143Leufs*5) heterozygous was identified, consistent with a predisposition to, or diagnosis of NOTCH2 related conditions including HCS (MedGen UID: 182961) and Alagille syndrome 2 (ALGS2) (MedGen UID: 341844).
Further inquiry revealed that the patient's daughter has facial features resembling those of her father and a history of patent ductus arteriosus (PDA), acroosteolysis. He also gave history of abortion of a female fetus with cardiac developmental defect. Genetic testing was advised for confirmation of the disease and subsequent management.
During his most recent follow-up visit, the patient was found to be doing well. He was on Prolia and was advised weight reduction, lifestyle measures, and exercise with stretch bands.