A 41-year-old man was admitted to our hospital because of 11 days of sudden discomfort and pain in the chest. Approximately 3 months previously, the patient experienced chest tightness and discomfort, lasting for approximately 5 min, during exercise, excitement, and emotional upset. These symptoms were relieved with rest. He also experienced fatigue and coldness. Eleven days before admission, he had sudden onset of chest tightness and crushing pain, which persisted without relief and did not radiate to the surrounding areas. On admission, the patient showed a dull facial expression and minimal attentiveness and concentration, and his skin was rough. A physical examination showed that his vital signs were stable. His blood pressure was 120/70 mmHg, heart rate was 85 beats/min with regular rhythm, and no pathological murmurs or pericardial friction rubs were heard over each valve area after auscultation. No obvious abnormal signs were observed in the lungs or abdomen, and there was no pitting edema in the bilateral lower extremities. He denied a previous history of hypertension or diabetes. An electrocardiogram performed on admission showed sinus rhythm, complete right bundle branch block, pathological Q waves in leads V1–V3, and T wave changes in some leads (). Color Doppler echocardiography revealed abnormal echoes in the mid and apical segments of the left ventricular anterior wall and segmental wall motion abnormalities, which were consistent with ultrasound features of coronary heart disease. The apex of the left ventricle was dilated at the right ventricular apex. The ventricular wall was thin and the thinnest area was 17 mm. The ventricular wall bulged outwards and downwards and it showed paradoxical movements. Mural thrombus was not observed, and a left ventricular apical aneurysm had formed. The left ventricular ejection fraction was 36%. Echocardiography showed left ventricular systolic and diastolic dysfunction (). Thyroid function tests showed the following: triiodothyronine (T3) level, 0.504 nmol/L; free triiodothyronine (FT3) level, 1.66 pmol/L; thyroxine (T4) level, 12.35 nmol/L; free thyroxine (FT4) level, 1.91 pmol/L; thyrotropin (TSH) level, 168.531 mIU/L; antithyroglobulin antibody (TgAb) level, 69.9I U/ml; thyroid peroxidase antibody (TPOAb) level, 486.9 IU/ml; total cholesterol (TC) level, 6.08 mmol/L; triglycerides (TG) level, 5.87 mmol/L; high-density lipoprotein cholesterol (LDLC) level, 0.97 mmol/L; low-density lipoprotein cholesterol (LDLC) level, 4.36 mmol/L; apolipoprotein A (apoA) level, 1.08 g/L; apolipoprotein B (apoB) level, 2.53 g/L; prothrombin time (PT), 14.9 s; international normalized ratio (INR), 1.14; activated partial thromboplastin time (aPTT), 57.8 s; thrombin time (TT), 111.2 s; fibrinogen (FIB) level, 3.23 g/L; aspartate aminotransferase (AST) level, 110 U/L; lactate dehydrogenase (LDH) level, 251 U/L; creatine kinase (CK) level, 169 U/L; creatine kinase-MB (CKMB) level, 10 U/L; hydroxybutyrate hydrogenase (HBD) level, 128 U/L; and troponin T level, 12.3 pg/ml. Ultrasound of the thyroid showed Hashimoto's thyroiditis. Coronary angiography showed that there was no obvious stenosis in the left main coronary artery. Additionally, 40–50% stenosis was found in the proximal LAD, plaques and MB were observed in the distal LAD, and forward flow was TIMI grade 3. There was no obvious stenosis in the left circumflex coronary artery or right coronary artery, and forward flow was TIMI grade 3 (). Left ventricular angiography, which was performed using a pigtail catheter, showed formation of ventricular aneurysm ().
The abovementioned findings suggested the diagnosis of coronary atherosclerotic heart disease, old myocardial infarction, and ventricular aneurysm formation. Acute myocardial infarction was excluded. On the basis of our findings of thyroid function tests showing decreased T3, FT3, T4, and FT4 levels and increased TSH and TPOAb levels, hyperthyroidism was excluded, and the diagnosis of hypothyroidism and Hashimoto's thyroiditis was made.
A total of 75 mg of clopidogrel with 100 mg of Bayaspirin was administered orally once daily to inhibit aggregation of platelets. Additionally, 20 mg of atorvastatin calcium tablets were administered orally once daily for lowering lipid and stabilizing plaques. Furthermore, a 23.7-mg metoprolol succinate extended-release tablet was administered orally once daily to slow down heart rate. The patient also received thyroid hormone replacement therapy (levothyroxine). The starting dose of levothyroxine was 12.5 μg/day with a progressive increase of 25 μg/day every 2 weeks. He was also treated with conservative medical therapy for ventricular aneurysm.
After 8 days of treatment, the chest tightness and pain of the patient were relieved, and he was then discharged. The patient was advised to follow a low-sodium, low-fat diet; take medications as prescribed; and exercise appropriately. He was not advised to consume foods containing iodine. He was asked to return to the clinic regularly every month to test thyroid function and to have echocardiography and thyroid ultrasound performed. The dose of levothyroxine was adjusted to 50 μg/day. Additionally, oral administration of clopidogrel (75 mg/day), Bayaspirin (100 mg/day), atorvastatin calcium tablets (20 mg/day), and metoprolol succinate extended-release tablets (23.75 mg/day) was continued. After 6 months of follow-up, thyroid function returned to normal. There was no complaint of chest tightness, fatigue, or coldness, and his skin was smooth and thin. He provided correct answers to asked questions, he had high attentiveness and concentration, and his condition further improved (). The patient refused to receive further cardiac surgery for left ventricular aneurysm.


The first patient was a woman in her 60s who was diagnosed with stage IIIB NSCLC (cT4N2M0 according to the eighth edition of the TNM classification). The primary tumor was >8 cm with hilar and mediastinal lymph node metastases detected using enhanced chest computed tomography (CT) and positron emission tomography (PET). Genetic testing showed no druggable alterations. The tumor proportion score for programmed death-ligand 1 expression was <1%. Although radical irradiation was considered, we decided against it because the estimated lung V20 was >35%. Instead, treatment with pembrolizumab plus platinum-based chemotherapy (carboplatin [CBDCA]) plus nab-paclitaxel (nab-PTX) was initiated. The primary site and lymph nodes underwent remarkable shrinkage after three cycles of this immunochemotherapy, and the recalculated lung V20 was 34.2%. Given this satisfactory shrinkage, we sequentially performed definitive concurrent CRT (CBDCA + PTX 2 cycles/RT [60 Gy/30 Fr]). Adverse events (AEs) during CRT comprised only grade 2 neutropenia as a hematological AE, and this was tolerable. After CRT, maintenance using durvalumab was initiated, and the patient completed 1 year of maintenance therapy without disease progression (Figure ).


The second patient was a man in his 60s who visited our hospital because of a chronic cough and mild respiratory difficulty. He was diagnosed with SCLC on the basis of histological analysis of a transbronchial biopsy. Enhanced CT and PET revealed a primary tumor in the right upper lobe and showed multiple lymph node metastases in the right mediastinum and right hilum. Pleural effusion was also noted. A cytological examination did not find malignancy in the pleural effusion, and he was therefore diagnosed with limited-stage SCLC.
The lung V20 in the radical radiation field was >35% (V20 was approximately 50%), and the patient was treated with systemic immunochemotherapy (atezolizumab + CBDCA + etoposide [ETP]). After two cycles of immunochemotherapy, marked shrinkage of the tumor was observed on CT, including the primary site and lymph nodes, which involved 15.0% of the lung V20. After completion of immunochemotherapy, the patient underwent concurrent CRT (cisplatin + ETP, two cycles/45 Gy) (Figure ). AEs during CRT were neutropenia, nausea, and esophagitis, all of which were mild (grade 2). At the time of writing this report, the patient has remained alive without tumor progression for over 1 year after completion of CRT.


A 14-year-old male with a history of asthma presented to the emergency room with isolated right frontal headaches that became worse with activity. There was no history of recent trauma and review of systems was otherwise negative. The patient was neurologically intact. An MRI of the brain demonstrated a large right MCF AC (Figure ). Neurology consult recommended conservative management of his headache. Ophthalmological exam revealed no papilledema and the patient was discharged with follow up imaging planned several weeks later.
On his routine follow-up CT head, a new right chronic SDH and a new left acute SDH was found (Figure ). He was brought in to the emergency room for evaluation where he was found to be neurologically intact but endorsed two recent episodes of morning emesis. Hematological workup was negative for bleeding disorders. Contrast-enhanced brain MRI revealed pachymeningeal enhancement and decreased AC size (Figure ).
Serial imaging remained stable and he was discharged with plans for repeat imaging. As of 3.5 years later, the patient is doing excellent clinically and his MRI brain demonstrates resolution of bilateral SDH and decreased size of the AC (Figure ). The patient remains asymptomatic and is doing well in school.


A 60-year-old woman was referred to our Urticaria Center of Reference and Excellence because of ColdU, from which she suffered since the age of 30. Localized pruritic wheals occurred when the ambient temperature was below approximately 18 °C for longer than 3-4 minutes, upon exposure to cold wind, or when touching cold objects. A cold provocation test (TempTest) was positive at a temperature of 18 °C and lower (). The dermatology life quality index was 16, indicating a large impact on her quality of life.
Her general medical history included hypertension and monoclonal B-cell lymphocytosis. The latter was diagnosed 7 years prior to presentation. A wait-and-see policy was maintained, since lymphocyte counts were stable during follow-up. The family history was negative for chronic urticaria and auto-inflammatory diseases. Treatment with at least 3 different H1-antihistamines at up to 4-fold of the standard dose, omalizumab dosed up to 600 mg every 4 weeks subcutaneously, and cyclosporin up to 5 mg/kg was unsuccessful. Because of the severe and refractory nature of her ColdU, further investigations were performed. This revealed type I cryoglobulins (monoclonal IgG), which were associated with the monoclonal B-cell lymphocytosis. No mutations associated with auto-inflammatory conditions were found with whole exome sequencing.
We hypothesized that, in this patient, the cryoglobulins detected were of pathophysiologic importance for her ColdU and started treatment with rituximab, a therapeutic monoclonal antibody directed against CD20 that reduces autoantibody production via depletion of memory B-lymphocytes. The patient received 2 intravenous administrations of 1000 mg rituximab with a 2-week interval. Three months later, the patient reported a remarkable improvement of her symptoms. She could now walk outside at a temperature of 8 °C for 3 hours and was able to touch cold objects without developing signs or symptoms of ColdU. Also, the cold provocation test was now negative (), the lymphocyte count normalized, and the cryoglobulin level decreased to 0.05 g/L (). At the time of writing, the complete response was still maintained 7 months after rituximab treatment, and cryoglobulin levels were decreased further, to 0.02 g/L.


We present the case of a 75-year-old male who was referred to the colorectal surgery clinic for evaluation after noting hematochezia, anal skin irritation, and rectal pain. Eight years prior, he had been diagnosed with leiomyoma of the rectum. At that time, he had undergone a biopsy of the lesion and local resection was performed several times. After each resection and biopsy, the pathology proved to be a benign leiomyoma.
Upon his latest presentation, eight years after initial local resection, a physical exam revealed a palpable mass at the anorectal junction. Biopsy of the mass was now consistent with leiomyosarcoma, including moderate atypia and a high mitotic rate (40 per 10 high power field), as compared to his previous diagnosis of leiomyoma (Figures -).
He underwent staging workup with an MRI of the pelvis (Figure ). This proved the mass to be 3.5 cm in diameter, located at the anorectal junction, with extension into the prostate and possible involvement of the urethra. The decision was made for the patient to undergo surgery. The colorectal team, combined with urological surgical teams, performed a robotic pelvic exenteration, which included cystoprostatectomy, abdominoperineal resection, and ileal conduit creation.
The final pathology resulted in a grade 2 leiomyosarcoma that invaded the prostate and skeletal muscle. Zero of 26 lymph nodes were positive. Incidentally, he was found to have Gleason 3+4 prostate cancer that was staged as pT2. The postoperative course was uncomplicated and he was discharged home from the hospital.
As an outpatient, he completed adjuvant radiation therapy to prevent local recurrence of his leiomyosarcoma. Complete surgical resection cured his prostate cancer, but urology will continue to monitor him for recurrence with interval PSA levels. As for monitoring of his leiomyosarcoma, he will continue to undergo regularly scheduled physical exams and imaging to assess the recurrence or development of metastatic disease. He is currently free of disease 18 months after surgery based on his most recent MRI scan and physical exam.


This is a case of a 71-year-old hypertensive and diabetic male with coronary artery disease status post percutaneous coronary intervention, idiopathic interstitial lung disease (ILD), and stage IVB diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy and radiation which lead to worsening of his ILD and the requirement of supplemental oxygen and daily low-dose steroid at home. Three months later, he developed a recurrence of his lymphoma and was started on salvage chemotherapy but his lung function continued to decline. Following three cycles of chemotherapy, he presented to the outpatient oncology clinic with a runny nose and nasal congestion, tested positive for rhinovirus, was breathing appropriately, and hence, was managed conservatively. After ten days, he presented to the emergency department with progressive dyspnea and hypoxia with minimal exertion at home with associated subjective fevers.
On arrival, he was tachypnoeic, tachycardic, febrile, and hypoxic. The examination was significant for rhonchi in bilateral lower lung fields and observed the use of accessory muscles of inspiration. Initial laboratory investigations and chest radiographs are described in Table and Figure , respectively. He was admitted to the medical floor and was placed on 4 liters of oxygen via nasal cannula and broad-spectrum antibiotics - azithromycin and cefepime for community-acquired- pneumonia. Computed tomographic imaging of the chest is described in Figure .
On the third day of admission, the patient was desaturated to the low 80s while on a non-rebreather mask, requiring him to be placed on a high-flow nasal cannula (HFNC), and he was transferred to the intensive care unit (ICU). Extensive infectious workup was negative: cultures - blood, urine, and fungal; beta-D-glucan, Aspergillus galactomannan; cryptococcal, legionella, Histoplasma and Blastomyces antigens; HHV-6, and CMV. His acute decompensation was thought to be from viral pneumonitis leading to ILD flare and he was started on high-dose steroids with notable improvement in his oxygen saturation. Steroids were gradually tapered, and he was transferred out from the ICU on day 16.
After five days of being on the floor, his respiratory status declined again. A chest radiograph is described in Figure . He was readmitted to ICU, placed on bi-level positive airway pressure (BiPAP), restarted on high-dose steroids and broad-spectrum antimicrobials - cefepime and vancomycin for hospital-acquired pneumonia. Repeat infectious workup was done and respiratory cultures returned positive for Stenotrophomonas maltophila and C. gleum. He was started on tigecycline and trimethoprim-sulfamethoxazole (SXT) which was changed to levofloxacin after three days because of hyponatremia and once the susceptibility patterns were available (Table ). His respiratory status continued to worsen, he declined intubation and opted for comfort care measures. He passed away eventually after the removal of BiPAP.


The first case is an HIV-negative, white, cis-gendered, 40-year-old male who engages in oral sex (received/performed) and anal sex (received/performed) with male partners. He does not use condoms or PrEP. He was last tested for STIs/HIV about 6 months ago and had a new sexual partner since. He is unsure if any of his sexual partners engage in injection drug use and does not report doing so himself, nor does he report sex work. Based on these practices, clinical guidelines would indicate that this person should receive HIV testing (serology and/or a point-of-care test), syphilis serology, and gonorrhea and chlamydia testing by urine and by oral and rectal swabs. The algorithm correctly identified these recommended tests. See .
Of note, if this person were to report being HIV-positive, then HIV testing is removed. See .


The fourth case is an HIV-negative, white, 32-year-old trans-male who has internal genitals. They engage in oral sex (performs only) and anal sex (receptive only) with partners who have external genitals. They report injection drug use and no sex work. They were last tested between 3 and 6 months ago and have had new partners since. According to current guidelines, trans-males are disproportionately affected by STIs/HIV and warrant comprehensive testing. Based on the identified risk practices, this person should receive gonorrhea and chlamydia testing (oral and rectal), syphilis, HIV, and hepatitis C serology, and an HIV rapid test. The algorithm identified such testing appropriately. See .


A 54-year-old woman diagnosed with HIV 30 years prior, and noncompliant with antiretroviral therapy (ART) over the past two years, presented to the hospital with persistent minimally productive cough and progressive dyspnea of 1-month evolution, associated with night sweats of 3-months evolution. She denied hemoptysis or unintentional weight loss, and review of systems was otherwise negative. She had a 20-year smoking history but had quit 2 weeks prior to presentation.
On exam, the patient had dyspnea and accessory muscle use when carrying on conversation and was visibly weak. However, the auscultatory chest exam was grossly unremarkable.
Initial lab analysis showed a markedly decreased CD4 count (28/mm3), and mildly elevated LDH (318 U/L), but was otherwise unremarkable, and a COVID-19 swab was negative. The initial chest radiograph showed multifocal hazy ill-defined opacities bilaterally (), and CT-chest imaging revealed bilateral nodular opacities in all lobes, with ground-glass halos, in both central and peripheral locations ().
The patient was started on broad-spectrum antibiotics and admitted for further workup and monitoring. Initial microbiologic workup showed acid-fast-bacilli smears negative × 3. Her initial sputum culture was positive only for Enterococcus faecalis × 2, and a Legionella urine antigen was positive, for which the patient was suspected of having Legionella pneumonia and switched to targeted antibiotic coverage (amoxicillin-clavulanate × 1 week; azithromycin × 3 weeks total).
Repeat imaging showed progression of bilateral lung nodules with both growth and cavitation appreciated (). Given the rapid evolution of disease, bronchoscopy with transbronchial biopsy was performed, revealing purulent discharge from the right upper lobe, and pathology showed acute and chronic inflammatory changes. No microorganisms were appreciated, DFA for Legionella was negative, and cultures, while sent 5 days after antibiotic initiation, were negative for Legionella and grew only Enterococcus faecalis, interpreted as a sputum colonizer.
Given the indeterminate nature of the histopathological findings and the positive Legionella antigen test, the patient was treated as presumptive Legionella pneumonia with a 6-week course of antibiotics. Clinical status significantly improved over the following days, and the patient was discharged within the week after being restarted on ART. On outpatient follow-up, the patient remained on ART and had complete resolution of her respiratory symptoms. Repeat imaging at 2-months postdischarge revealed near-complete resolution of consolidations and cavitations previously seen.


In February 1996, a 40-year-old Caucasian woman consulted an orthopaedic surgeon because of persistent pain in the right foot. On radiograms, a lytic tumoral process was discovered in the right os naviculare. Curettage was performed, and anatomopathological revision of the obtained tissue at the Mayo Clinic Rochester (Dr. Unni) confirmed the diagnosis of a clear cell chondrosarcoma (). In June 1996, local progression of the disease was discovered and an amputation of the right lower leg was performed. Subsequently, she was followed with annual chest X-ray examination and clinical examination by her treating orthopaedic surgeon.
In April 2016, her chest radiogram showed a new dense opacity in the left upper lung lobe. On CT scan, two opacities in the left upper lobe were detected, with a diameter of 6 mm and 3 mm, respectively (). After multidisciplinary consultation, close follow-up was advised given the aspecific and small diameter of the lesions. Three months later, only one lesion remained on CT scan. Further follow-up with annual radiograms was organised. In December 2019, a slight increase in diameter in the nodule in the left upper lobe was seen. Subsequently, a new CT scan was performed, which showed a single nodule of 13.5 mm. Apart from a dry cough, the patient was asymptomatic at the time of this finding. A lung function examination was performed and showed no abnormalities. Further staging with an abdominal CT showed no other lesions suspected for metastases. There was no history of smoking. A CT-guided lung biopsy was performed, and the patient was referred to our tertiary sarcoma centre for further diagnostic examination and treatment because of the probable diagnosis of a chondrosarcoma metastasis.
At the time of referral, the patient was in good health and had no symptoms other than a transient dry cough. She did not have complaints of weight loss or exhaustion. Clinical examination showed no abnormalities besides the lower right leg amputation after surgery for the chondrosarcoma.
Histopathological examination of the lung biopsy showed the presence of an atypical chondroid tumoral proliferation composed of atypical spindled to rounded chondroid cells embedded in a chondroid matrix (). No obvious clear cell morphology, high-grade cytonuclear atypia, or mitotic activity was observed in this biopsy. Immunohistochemically, the atypical cells showed a diffuse expression of S100 and Podoplanin (D2-40). These morphological and immunohistochemical findings were suspected for a metastasis of a chondrosarcoma.
After discussion in our multidisciplinary bone and soft tissue sarcoma board, a video-assisted thoracoscopic wedge resection was performed. Histopathological examination of the resected lung nodule showed a 15 mm large, well-circumscribed chondroid tumoral proliferation composed of atypical rounded cells with a centrally placed, large round nucleus and abundant clear to slightly eosinophilic cytoplasm. Intermingled within these atypical clear cells, osteoclast-like giant cells, a chondroid matrix, and calcifications were observed. The atypical cells stained strongly with antibodies against S100 and Podoplanin (D2-40), further confirming the diagnosis of a lung metastasis of the known clear cell chondrosarcoma ().
She recovered well from surgery. Given the extended time frame between the primary tumor and the development of this single lung metastasis (20 years) and the insensitivity of clear cell chondrosarcomas to chemotherapy, a conservative approach was held with regular imaging as follow-up, meaning a chest CT every six months during the first year.


A 55kg, 11-year-old male underwent a right craniotomy and frontal lobectomy for resection of a seizure focus identified by prior intraoperative subdural EEG electrode grid application four days prior. The patient’s previous history was significant for pansinusitis complicated by right holohemispheric subdural empyema and thrombosis of the anterior third of the superior sagittal sinus in January 2019. This was treated with antibiotics and a right frontal craniotomy. In April of 2020, he developed seizures that were fulminant in presentation and rapidly became intractable. Seizure semiology included poor attention at school, body stiffening episodes, and periods of “spacing out.” The increase in seizure frequency had resulted in worsening academic performance (A to C student), blunting of effect, inability to continue with soccer, and impaired peer relationships. He was scheduled for right frontal lobe resection for focal, lesional epilepsy.
On the morning of surgery, he received his scheduled valproic acid and levetiracetam but experienced breakthrough seizure activity immediately prior to surgery. Therefore, he was transferred from the Pediatric Intensive Care Unit to the operative suite urgently. The patient was induced with rocuronium and propofol for endotracheal intubation. Maintenance included total intravenous anesthesia (TIVA) with propofol and remifentanil infusions in order to accommodate the need for intraoperative neuromonitoring. The case proceeded uneventfully for 12 hours, and approximately one hour prior to the conclusion of surgery, the propofol and remifentanil infusions were discontinued. The total propofol dose throughout the case was approximately 2500 mg. Sevoflurane was initiated at 0.5 MAC in order to expedite emergence. Of note, these actions correlated with the conclusion of neuromonitoring and the beginning of dural closure. During the closure, the patient exhibited gross signs of full-body rigors. In the absence of neuromonitoring, seizure activity could not be confirmed or refuted by that diagnostic modality. At the request of the neurosurgeon, 2 mg of midazolam and 500 mg levetiracetam were given. Despite the cessation of all anesthetics for almost one hour, the patient failed to exhibit spontaneous respiratory effort or response to oral and tracheal suctioning. It also appeared that the patient had a downward gaze of his eyes, but pupillary reflexes were intact. He was brought directly from the operating room to CT to identify a possible post-surgical cause for his delayed emergence.
CT revealed left to right midline shift into the surgical bed with diffuse loss of grey-white differentiation thought to reflect cerebral and cerebellar edema. The surgeon performed a bi-frontal craniotomy for reexploration based on these findings, which did not reveal a definitive cause. After the surgery, the skull fragment was not replaced in order to accommodate for swelling. The patient’s neurologist was consulted in the OR, and a loading dose of 1000 mg of intravenous fosphenytoin was recommended and administered. The patient remained hemodynamically stable throughout both anesthetics. The patient was transferred to the PICU with plans to maintain deep sedation, ICP monitoring, and continued aggressive seizure prophylaxis for at least 48 hours or until brain edema decreased. Results of an MRI without contrast obtained later that evening included “extensive cerebral and cerebellar edema without evidence for cytotoxic edema. The possibility of toxic or metabolic etiology is favored, florid posterior reversible encephalopathy syndrome (PRES) could also be considered”. The patient had an uneventful ICU course; no observed seizure activity, continuous negative EEG, normal neurologic exams, and was extubated on a postoperative day four after sedation with fentanyl and midazolam infusions weaned, and extubation criteria met. Upon discharge, a non-focal neurologic exam was elicited. The patient exhibited no neurologic sequelae at subsequent outpatient follow-up visits with his neurologist with a significant improvement from his baseline symptoms and was free to resume all activities.


A 15-year-old female underwent minimally invasive transaxillary thyroidectomy due to a diagnosed right thyroid lobe nodule. Immediately after the surgery, she experienced shoulder and elbow paralysis and hoarseness. Examination indicated severe upper trunk plexopathy, brachial plexus injury with upper trunk rupture, and right recurrent laryngeal nerve injury. She was referred to Sina Hospital, Tehran, Iran in winter 2020 after 30 sessions of unsuccessful physiotherapy to reconstruct.
All the procedures and possible outcomes discussed and she and her parents signed informed consents to start reconstructive treatments. During first surgery, through medial proximal right arm incision, nerve fascicles transferred from the ulnar nerve to the biceps brachii of the musculocutaneous nerve and from the median nerve to the brachialis branch of the musculocutaneous nerve ().
About three weeks later, in the second surgery, via posterior approach, with a transverse incision in upper scapula border the spinal accessory nerve was transferred to the suprascapularis nerve under the microscope coaptation (). Next, through an incision of posterior arm, the radial branch of the long head of the triceps brachii was identified using the nerve stimulator and eliciting triceps muscle contraction, and this nerve was transferred to the anterior branch of the axillary nerve under the microscope (). She had been under strict nerve stimulation and physiotherapy for about 4 months and fortunately gained most of shoulder and elbow activities accordingly.


We present a 23 yr old man with chief complaint of facial asymmetry. He had past medical history of left hemifacial lymphatic malformation that underwent surgery in childhood. During surgery buccal branch of left facial nerve was injured. After surgery gradually patient developed dentofacial deformity. After puberty patient underwent prolonged orthodontic treatment (pre and post-op), bimaxillary surgery, genioplasty, mandibular body and angle implants.
In clinical examination his facial countur was not optimal and there was no mouth opening limitation and his occlusion was acceptable with slight deviation of the mandible to the left. Totally patient was asymptomatic. We requested maxillofacial CT-scan. CT-scan revealed intrusion of left mandibular condyle into middle cranial fossa (). Because patient was asymptomatic we did not do any surgical Intervention and we decided to follow him regularly.
Informed consent was obtained from the patient. (Ethical Code: IR.SUMS.REC.1400.403).


A 50-year-old man visited the emergency department with persistent right upper quadrant pain and vomiting. He was a chronic alcoholic who drank 1 or 2 bottles of Soju daily and often vomited after drinking. Before presentation, he had an episode of vomiting while brushing his teeth, with associated severe abdominal pain with a numerical rating scale of six points. Tenderness and rigidity were noted on physical examination of the upper abdomen. He had a medical history of hypertension and dyslipidemia. At the time of hospital visit, his vital signs were stable with a blood pressure of 150/100 mm Hg, pulse rate of 95/min, respiration rate of 18/min, and body temperature of 36.6°C. No significant findings were noted in the initial blood tests, including complete blood count, blood chemistry, cardiac markers, and C-reactive protein. Abdominal computed tomography (CT) showed extraluminal air bubbles around the paraesophageal area, esophagogastric junction, and a focal wall defect of the lower esophagus (Fig. ). On the basis of the clinical history and CT findings, Boerhaave's syndrome was suspected. After the immediate commencement of systemic intravenous antibiotics, laparoscopic surgery was performed for the esophageal perforation. On the surgical field, an approximately 5 cm sized laceration, extending through one-third of the wall's thickness, was noted at the gastroesophageal junction (Fig. ), and primary closure was performed using the monifix and omental patch. After the operation, he was fasted for 5 days and given parenteral nutrition, which relieved his pain.
On the fifth day postoperation, esophagography showed extraluminal contrast leakage at the anastomotic site. Esophagoscopy showed an approximately 15 mm perforation at the site of the anastomosis at the esophagogastric junction. Endoscopic closure with OTSC was initially performed for the primary closure (Fig. A); however, effective closure was difficult due to scarring and presence of fibrotic tissue around the perforation site, which prevented efficient suctioning of the surrounding area. An anti-migration covered metal stent was planned as a secondary treatment, as he had a high fever of 39°C, and a follow-up esophagography showed persistent extraluminal contrast leakage at the anastomotic site. A 6 cm anti-migration covered metal stent (Hanaro Shim's stent, M.I.Tech Co., Ltd., Gyeonggi-do, Korea) was successfully placed at the gastroesophageal junction (Fig. B). To prevent stent migration, a nylon thread, which was connected to the proximal part of the stent, was hung around the patient's ear. Despite efforts to prevent stent migration, the stent dislodged into the stomach five days after the procedure. Fortunately, extraluminal contrast leakage was not observed on follow-up esophagography, and extraluminal air bubbles around the site of the anastomosis had decreased on abdominal CT. There were no specific findings in his clinical symptoms and laboratory tests; therefore, he was discharged with an assessment of improvement of postoperative anastomotic leakage after stenting.
However, 9 days after discharge, he was re-hospitalized on account of abdominal pain and fever. Blood tests showed increased inflammatory markers with a C-reactive protein of 4.9 mg/dL (0–0.5, normal range). Esophagoscopy showed a perforation at the anastomosis site, and an approximately 2.5 cm slender leakage tract was traced when a contrast dye was injected into the perforation site (Fig. A). As a rescue treatment, 2.0 cc of N-butyl-2-cyanoacrylate (Histoacryl, B. Braum Korea Co., Ltd., Seoul, Korea) and lipiodol mixture (at 1:1) was injected into the leakage tract through the perforation (Fig. B). He showed improvement in the abdominal pain and on laboratory findings a day after the procedure. On the second day after operation, he started a clear liquid diet and was fine with a full liquid diet on the third day. Finally, the patient was discharged on solid diet and oral antibiotics. A month after cyanoacrylate treatment, a complete scar formation was observed at the previous perforation site, and the previous anastomotic leakage site had healed completely (Fig. ). Up to now, the patient has been followed up at the outpatient clinic for eight months without recurrence.


A 76-year-old female presented to the clinic with a several-month history of numbness in the left half of her face - forehead, cheek, and chin - accompanied by sharp shooting pain. It was also characterized by a prominent lack of sensation of the left upper and lower gums and the inside of the cheek pouch, without inadvertent painless cuts. Taste and salivation were unaffected. She also complained of a dry and itchy left eye, which had been treated with saline eye drops, and an unintentional weight loss of 10 pounds over the past year. There were no complaints related to vision, swallowing or speech difficulty, or acral numbness.
Her past medical history was significant for a two-year history of idiopathic polyarthritis treated successfully with hydroxychloroquine 200 mg twice daily. Additionally, she had a history of breast cancer requiring a lumpectomy and six cycles of chemotherapy with Taxotere and cyclophosphamide, completed in 2012, followed by radiation therapy. She was noted to be in remission with regular screening for malignant disease, with a recent negative positron emission tomography (PET) scan. She was on maintenance tamoxifen therapy 20 mg daily. Her other medications included vitamin D supplementation and once-monthly intramuscular injections of 1-mg vitamin B12. She had no history of smoking and denied any fatigue, headaches, shortness of breath, or other constitutional symptoms.
She was 5 feet 6 inches tall, weighed 114.1 pounds, with a body mass index of 18.4 kg/m2. Her vitals revealed a blood pressure of 172/90 mmHg, a heart rate of 63 beats per minute, and oxygen saturation of 98%. On physical examination, the patient appeared thin but well-nourished and in no acute distress. She was oriented to person, place, problem, and time with appropriate mood and affect. Gait stance and cadence were normal. Tandem walking was normal and the Romberg sign was absent.
The cranial examination revealed hypesthesia to touch in the V1, V2, and V3 distribution of the left trigeminal nerve. The corneal reflex was preserved to touch. The masseter function was also preserved with clenching of the teeth, but there was bilateral wasting of the temporal fossae. Motor function of the left seventh cranial nerve was entirely normal to forehead elevation, smiling, and blowing of the cheeks. Pterygoid function with jaw deviation and masseter function with teeth clenching were also normal. The rest of the cranial nerve examination was normal.
Motor function of the upper and lower extremities revealed normal muscle bulk and tone, and a 5/5 motor response on the Medical Research Council (MRC) rating scale. The handgrip was symmetric without pronator drift. Skeletal examination of the joints, bones, and muscles showed no signs of contractures, malalignment, tenderness, or bony abnormalities and there was a normal range of all extremities. Deep tendon reflexes were intact in both upper extremities. Deep tendon reflexes at the ankles bilaterally were absent. No spastic catch was noted in the arms and the plantar Babinski sign was absent bilaterally. Coordination with finger-to-nose and heel-to-shin was normal bilaterally. Sensory examination was normal to touch-pressure, vibration, and joint-position-sense in the fingers and toes.
An MRI of the brain with and without contrast revealed an 11-mm enhancement of the left mandibular nerve within the left foramen ovale on T1-weighted sequences (Figure ).
A lumbar puncture with cerebrospinal fluid (CSF) analysis was performed and the findings are summarized below (Table ).
Oligoclonal banding testing was performed by using isoelectric focusing (IEE) and immunoblotting. Zero oligoclonal bands were observed in the CSF. However, four paired bands were observed in both the CSF and serum. Paired bands suggest an immune response to an inflammatory process outside the central nervous system (CNS) and are unlikely to represent a CNS inflammatory disease.
Sjögren’s syndrome serology testing revealed findings that are summarized below (Table ).
Furthermore, a serum paraneoplastic panel including anti-acetylcholine receptor ganglionic neuronal antibodies, anti-amphiphysin antibodies, anti-glial nuclear antibody type 1, anti-neuronal nuclear antibody type 2, anti-neuronal nuclear antibody type 3, collapsin response-mediator protein-5 (CRMP-5) immunoglobulin G, neuronal voltage-gated potassium channel antibodies, calcium channel antibody P/Q-type and Purkinje cell cytoplasmic antibodies were all found to be negative. An ear-nose-throat (ENT) referral and evaluation revealed no cervical adenopathy or neck masses.
Our provisional diagnosis was Sjögren's syndrome-associated trigeminal neuropathy based on the sicca symptoms of dry eyes, the positive serology for Sjögren's syndrome, trigeminal ganglion and mandibular nerve enhancement, and prior history of hydroxychloroquine-responsive polyarthritis. Significantly, a PET scan was negative for metastatic disease given her prior history of breast cancer. Furthermore, an ENT evaluation precluded the presence of a head-and-neck malignancy. Interestingly, CSF analysis revealed four oligoclonal bands in both serum and CSF, implying a systemic autoimmune disease, supporting the diagnosis of Sjögren's syndrome. The patient was given a titrating dose of prednisone at 0.5 mg/kg for one month without relief of facial numbness and dysesthesias. A course of duloxetine at 60 mg a day improved the neuropathic symptoms of dysesthesia and sharp tingling pain.


A 72-year-old male presented with a two-day history of right upper quadrant pain on a background of a metastatic, small bowel, well-differentiated NET diagnosed 5 years previously. The tumour was a low-grade mesenteric NET with a ki67 of 8% at diagnosis. He had multiple liver metastasis, which were stable. Carcinoid syndrome was well controlled on a long-acting, monthly dose of a somatostatin analogue with last dose being 28 days prior to presentation and due in three days. His comorbidities included hypertension, an infrarenal aortic aneurysm and chronic obstructive pulmonary disease. He presented with right upper quadrant tenderness and the liver edge was palpable 4 cm below the costal margin. Initial blood tests showed a white cell count of 18.9 × 109/L, C-reactive protein 212 mg/L and liver function tests within normal limits. Vital signs were reassuring, and an abdominal ultrasound described a thickened gallbladder wall, mobile sludge and an 8.5-mm common bile duct suggestive of cholecystitis (). Computerised tomography (CT) of the abdomen was noted to show multiple segment V liver masses with capsular deformity suggestive of central necrosis. He was initially managed with analgesia and intravenous piperacillin-tazobactam. After a discussion with the patient and consultation with his treating oncologist regarding his relatively stable disease burden and reasonable prognosis, a laparoscopic cholecystectomy was performed.
During cholecystectomy, extensive carcinoid metastases were encountered (). To perform the operation laparoscopically required retraction of the left liver lobe. However, the liver was stiff and inflamed making exposure of the biliary tree difficult. The gallbladder was mobilized, a critical view of safety and an unremarkable intraoperative cholangiogram was obtained. The length of the operation was 1 h and 35 min. Histopathology of the gallbladder showed benign, chronic outlet obstruction, patchy serosal mixed inflammation and one lymph node containing metastatic disease.
During the procedure, the patient developed a persistent tachycardia and an octreotide infusion was initiated. He developed hypotension, wheeze, sweating, bronchospasm and flushing. Venous pH was 7.14. Electrocardiogram showed pronounced ST-segment elevation in leads V3 and V4, multiple ventricular ectopic beats, bigeminy and bundle branch block. Troponin levels rose to >50 000 ng/L. A bedside echocardiogram showed hyperdynamic left ventricular function and septal regional wall abnormality. Profound vasodilatory and cardiogenic shock resulted requiring vasopressin at 6 mL/h (0.04 IU/min) titrated over 7 hours and noradrenaline at 5 mL/h (5ug/min) titrated over 6 h. Later, cardiac angiography showed minor coronary disease and within 24 h, he was extubated, his pain resolved, and inflammatory markers had normalised within 48 h.


A 60-year-old African American female with a past medical history of hypertension, chronic obstructive pulmonary disease (COPD), hyperlipidemia, sickle cell trait, class III obesity, presented to the hospital with shortness of breath two days ago, associated with a progressively worsening tongue and neck swelling that developed for five days. She was referred to the emergency room from her Primary Care Physician (PCP) office for high clinical suspicion of angioedema. Earlier that day the patient had presented to her PCP office with a progressively worsening, asymmetric (right greater than left) tongue swelling for five days. The tongue swelling had disrupted the patient's sleep and made it difficult for her to swallow solid food. She also endorsed associated painful neck swelling and shortness of breath. She did not notice any rash on her body and denied itching. She also reported having a dry cough for two months, which was persistent despite trying all cough remedies. Her home lisinopril was discontinued four weeks ago with some improvement of cough. She had previously tolerated ACE inhibitor for months without any issue. Upon arrival at the hospital, on physical examination, her vital signs included a temperature of 37.1ºC, blood pressure of 164/89 mmHg, heart rate of 102 beats per minute, respiratory rate of 22 breaths per minute, and oxygen saturation of 93% on room air. She was alert and oriented, speech and voice with wet quality, without stridor, head and neck exam was significant for lower lip swelling, diffuse neck swelling with tenderness, palpable cervical, and retro auricular lymph nodes. A heart exam revealed regular rate and rhythm. Lung examination was notable for decreased air entry bilaterally without any added sounds. Skin exam was without evidence of any erythema, swelling, or rash. The remainder of the examination was unremarkable. Her initial lab work including a comprehensive metabolic panel and complete blood count were within normal limits. Her erythrocyte sedimentation rate was elevated at 59 mm/hr. An initial chest x-ray and x-ray of the soft tissues of the neck were unremarkable. A clinical diagnosis of angioedema related to either ACE inhibitor use or other etiology was made. The patient immediately received steroids, histamine 2 (H2) receptor blockers, Icatibant, and fresh frozen plasma. The patient was evaluated by an otolaryngologist with transnasal flexible fiberoptic laryngoscopy (FFL), which revealed symmetric bilateral watery edema on the lateral edges of the lingual surface of epiglottis without evidence of laryngeal involvement. She was transferred to the Intensive care unit for closer monitoring and anticipated intubation. Further lab testing revealed normal C-1 esterase levels, complement C3 levels, complement C4 levels, and C-reactive protein. The patient’s symptoms persisted on the next day and a repeat FFL evaluation remained unchanged from prior. A computed tomography scan with intravenous contrast of the soft tissues of the neck was obtained which revealed an unremarkable exam of pharyngeal mucosal spaces, larynx, and neck spaces. She was started on antihistamines, H2 receptor blockers, and steroids. The patient received a total five-day course of steroids and had resolution of swelling without requiring intubation. In the absence of associated itching, hives, and normal C-1esterase levels; bradykinin mediated angioedema in the setting of prior ACE inhibitor use was deemed the cause of her angioedema. ACE inhibitor-induced angioedema was permanently added to the list of her allergies. She was transferred to a regular medicine floor within three days and discharged home after a seven-day hospital course with an outpatient follow-up with PCP.


A 48-year-old male with a past medical history of alcohol use disorder, myeloid sarcoma, and AML presented to the emergency department complaining of dizziness, fatigue, and fever after receiving cytarabine chemotherapy earlier in the day. He denied chest pain, abdominal pain, nausea, vomiting, headaches, and leg swelling. Of note, five months prior, the patient was diagnosed with AML, which presented as myeloid sarcoma, and he was subsequently started on chemotherapy with idarubicin and cytarabine. The patient’s initial vital signs included a temperature of 99.1 F, pulse rate of 112, respiratory rate of 30, and blood pressure of 101/61 mmHg. Physical examination was notable for pale conjunctiva, tachypnea, slow capillary refill, and tachycardia; the remainder of the examination was unremarkable.
The patient's laboratory findings are shown in Table , demonstrating leukocytosis with bandemia, severe anemia, severe thrombocytopenia, decreased lymphocytes, elevated metamyelocytes, and elevated myelocytes. The patient was given 1 unit of packed red blood cells for symptomatic anemia and started on vancomycin 1.25 g intravenously (IV), cefepime 1 g IV, and azithromycin 500 mg orally (PO) for empiric broad-spectrum antibiotic coverage due to concerns for sepsis. Shortly after the transfusion, the patient was found to be persistently tachypneic with respiratory rates greater than 30 and had difficulty completing his sentences; consequently, he was started on bilevel positive airway pressure via a face mask. A chest x-ray (Figure ) and computed tomography (CT) of the chest with intravenous contrast (Figure ) was obtained and revealed diffuse bilateral, ground-glass opacities, which was concerning for transfusion-related acute lung injury (TRALI) given the recent transfusion. Due to the patient’s increased work of breathing and impending respiratory failure, the patient underwent elective endotracheal intubation and was admitted to the intensive care unit (ICU).
Despite halting blood product transfusions for several days, the patient’s respiratory status worsened, evidenced by progressively increasing requirements of fraction of inspired O2 levels, positive end-expiratory pressures, and peak inspiratory pressures. The patient’s white blood cell count continued to increase despite broad-spectrum antibiotics and a negative sputum culture. His hemoglobin levels were persistently less than 5, prompting a bronchoscopy with bronchoalveolar lavage, which revealed progressively bloody effluent on serial lavage. As a result, a diagnosis of DAH was made, and the patient was started on a five-day course of methylprednisolone 1000 mg IV. The hematology and oncology specialists reviewed the patient’s case and concurred with the diagnosis of DAH and recommended blood product transfusion as needed to maintain a hemoglobin level of >7 g/dL and a platelet count of >20,000 cells/μL.
During the subsequent days of his ICU course, the patient had difficulty weaning from mechanical ventilation, despite transfusion of blood products and empiric antibiotic coverage. Repeat chest x-rays did not reveal improvement in the patient’s bilateral pulmonary infiltrates. Repeat sputum and blood cultures were negative. The patient was later found to be in asystole on telemetry and, unfortunately, resuscitative measures failed to rescue the patient.


A 38-year-old female presented to us complaining of pain and stiffness of her left ring finger for six weeks. She had a history of fracture of the affected finger following a minor injury initially treated with splinting for six weeks at another hospital. Subsequently, she was treated with hand therapy, and serial radiographs were done regularly.
The lateral view (Figure ) and oblique view (Figure ) of the left ring finger show a fracture at the base of the proximal phalanx of the ring finger.
The fracture is seen through an abnormality in the metaphyseal region of the proximal phalanx with an associated nonaggressive expansile lytic lesion without cortical breach. There is no associated periosteal reaction, matrix calcification, or ossification. The subsequent follow-up images at two months (Figure ) show a near-complete consolidation of the fracture callus at the base of the proximal phalanx of the ring finger. Six months later (Figure ), there is a bony union at the fracture site. Still, the lytic lesion persists with sclerosis in the distal half of the lesion at six months.
After six months, she underwent a curettage of the enchondroma and reconstruction with a bone graft (freeze-dried allograft). Following surgery, the hand was splinted for six weeks, and hand therapy was started a few days after surgery. She regained almost complete range of motion at one year (total active motion (TAM): 240°), QuickDASH score of 15/100, and no tumor recurrence. The X-ray image at 15 months follow-up showed good bony consolidation and incorporation of bone graft with no recurrence of enchondroma (Figure ).


A 57-year-old male presented in 2009 with sudden onset aphasia, with a brain MRI demonstrating a 39x34x32mm left parietal cystic mass with ring enhancement. He underwent cyst fenestration with subtotal tumor debulking and was diagnosed with a left parietal GBM, WHO Grade IV. The tumor showed >50% MIB-1 positivity and was positive for GFAP and S-100. MGMT and IDH1 status were not available. Although the tissue was banked and re-reviewed to confirm the diagnosis at a future date, further genetics were never performed on this sample. He received Gamma Knife (GK) SRS to the left parietal target (32x35x33mm) with 16Gy to the 50% isodose line (IDL). He then received intensity-modulated radiation therapy (IMRT) to a dose of 45Gy in 25 fractions (fx) to the left parietal resection bed and residual tumor with a margin with concurrent temozolomide (TMZ), completed three months after surgery. Imaging following his radiation course showed reaccumulating fluid within the cystic component of the mass, and two months later, an Omaya reservoir was placed within the mass to drain fluid as symptoms required. He had clinical and radiographic signs of infection of the Omaya reservoir one month after its placement and had it removed, followed by a course of antibiotics. Unfortunately, he presented again one month later with signs of cranial infection, which required washout and an additional antibiotic course.
He was planned for 6-12 cycles of adjuvant TMZ and had completed two cycles of TMZ before his course of infections. Three months after the Omaya reservoir was removed, when he was deemed clinically stable, he was considered for resumption of his TMZ adjuvant therapy. However, a brain MRI completed at this time showed signs of disease progression. As a result, he was transitioned to bevacizumab and irinotecan combination therapy for 20 months, followed by bevacizumab as a single agent for 15 months, which was stopped due to proteinuria.
His disease remained stable on serial imaging for approximately six years when a brain MRI showed signs of disease progression. He underwent a left posterior parietal subtotal resection four months later, with pathology showing an IDH wildtype astrocytic neoplasm, with some similarities to his prior GBM pathology. MGMT was not evaluated on this specimen. Of note, given the unusual disease course, his original pathology was retrospectively reviewed at this time, and it was confirmed that he did initially have GBM. On multidisciplinary review of the case, this was considered as a recurrence. He later developed hydrocephalus and underwent right frontal ventriculoperitoneal shunt placement shortly after the surgery. He was then restarted on bevacizumab one month later, which was stopped after eight months when a brain MRI showed four new lesions, each under 2cm, suspicious for recurrence. He underwent GK SRS to all four lesions with 15Gy to the 65% IDL to the right occipital lobe, 14Gy to the 50% IDL to the left occipital lobe, and 14Gy to the 50% IDL to two left temporal lobe lesions. This was followed by a cycle of pembrolizumab, which was subsequently stopped due to severe diarrhea, and he continued without systemic therapy. Four months after his prior GK treatment, he was found to have five new lesions in the corpus callosum, pineal region, left temporal lobe, and two lesions in the left occipital lobe, which were each treated with GK SRS with 14Gy to the 50% IDL, 14Gy to the 50% IDL, 14Gy to the 80% IDL and 14Gy to the 60% IDL, respectively.
Use of GammaTile
His follow-up brain MRI, which occurred three months after his last GK treatment, showed a good response of the previously treated lesions as they were overall stable in size. However, when compared to the prior GK treatment planning MRI, there was an increased enhancement in the left temporal lobe anterior to the prior GK treatment location. On multidisciplinary review, this was thought to represent tumor recurrence rather than radiation necrosis. Additionally, he was doing well clinically with no new neurologic deficits on examination and a Karnofsky Performance Status of 90. He was not on systemic therapy, dexamethasone, or anti-epileptics. He was deemed a good surgical candidate and once again was planned for resection of this recurrent lesion with consideration of additional radiotherapy. Given the location of the recurrent disease within the 45Gy volume of the initial IMRT plan and additional dose overlap with multiple prior GK SRS treatments, EBRT options were felt to carry an unacceptable risk of radiation necrosis. As an alternative, the patient was offered resection followed by intracranial brachytherapy with Cesium-131 seeds (GammaTile) implantation. The radiation oncologist reviewed the T1 weighted preoperative MRI with gadolinium to determine the number of tiles needed for the procedure. This was estimated based on the preoperative gross tumor volume and the anticipated cavity volume that would require coverage with 60Gy prescribed to a 5mm depth. Following this assessment, eight GammaTiles containing 32 Cs-131 seeds were preordered before the expected date of surgery. A comprehensive reported protocol, similar to what was completed for this patient, has been published by Ferreira et al [].
The patient underwent maximal safe resection and GammaTile placement shortly after this recurrence was discovered. On the day of surgery, numerous tissue samples from various areas of the resection cavity were sent to the frozen section to confirm which areas had tumor relative to radiation necrosis. Maximal safe resection occurred but was limited due to the proximity to the Wernicke’s area and the visual cortex. The surgeon placed a total of eight GammaTiles containing 32 Cs-131 seeds with the assistance of the radiation oncologist. The placement was guided based on the results of the prior biopsies, which identified which areas of the resection cavity had tumor. The placement was evenly spaced with no overlapping GammaTiles in an arrangement sufficient to cover the full extent of the treatment area. The procedure was completed successfully over five minutes. The operative room was surveyed before, during, and after the procedure with no detection of radioactivity above background levels. Post-operative MRI confirmed subtotal resection. Post-operative MRI was then fused with the post-implant CT to determine dose distribution and target coverage. A CT simulation was performed using 1mm slice thickness, and the brachytherapy seeds were delineated by the physicist and confirmed by the radiation oncologist. The gross tumor volume (GTV) was defined as the operative bed adjacent to the placed tiles and expanded 5mm to create a clinical target volume (CTV) to which 60Gy was prescribed to a 5mm depth. The post-implant dosimetry was calculated using the Eclipse™ treatment planning system (Varian Medical Systems Inc., Palo Alto, California). An axial slice from this treatment plan can be seen in Figure . The patient was discharged two days after the operation without any complications. Molecular testing was completed on the resected sample following the surgery and showed the tumor to be IDH wild type and MGMT methylated. The final pathology suggested a high-grade astrocytoma. However, in the context of the patient’s prior history and specimens, pathology felt the lesion was compatible with recurrent GBM.
The patient was seen two weeks following the procedure by neurosurgery with subjective complaints of new-onset double vision without any new visual deficits on examination. Shortly after, he presented to the hospital with complaints of nausea, vomiting, aphasia, and weakness. He underwent a CT Head, which was normal, and was placed on dexamethasone 4mg BID, which largely improved his symptoms. One month later, he reported back pain, which prompted an MRI of the spine that revealed diffuse leptomeningeal disease (LMD), most prominently in the thoracic spine. He was treated from T5 to T12 with a dose of 20Gy in five fractions with a three-dimensional conformal radiation therapy plan. Around the same time, he reported worsening of speech and right-sided weakness. A brain MRI showed numerous areas of recurrence and a new mass-like T2 fluid-attenuated inversion recovery (FLAIR) signal abnormality measuring 4.6 x 5.4 x 5.6 cm in the left frontal lobe with extension across the corpus callosum. In the parietal resection cavity where GammaTiles were placed, there was increased enhancement reflecting recurrent disease or inflammatory changes.
A few weeks later, the patient saw neurosurgery and medical oncology and reported worsening aphasia, fatigue, and right-sided weakness. He declined additional treatment and transitioned to comfort care and hospice. He later passed away approximately 11.5 years since his initial GBM diagnosis.


A 30-year-old male presented to our surgical outpatient department after being referred from the medicine department with a complaint of morbid obesity. The patient had obstructive sleep apnea, impaired glucose tolerance and hypertension that was difficult to control on antihypertensive medication. The patient had a BMI of 81.2 kg/m2 (258 kg) and has own hotel business. Initially, pharmacological treatment along with physical activity was started by the medicine unit, but the patient’s weight and symptoms were refractory to conservative management. He was investigated, and his hormonal profile was normal. The patient had been married for four years and had one child and a normal reproductive life. Bariatric surgery was planned in a multidisciplinary meeting that included the surgery, anaesthesia, medicine and cardiology departments. The patient and his family were informed about the benefits and risks of the treatment, and the patient underwent laparoscopic sleeve gastrectomy in 2014, which was successful; the immediate post-operative period was unremarkable, and the patient was discharged home with multi-vitamins and in order to maintain a proper calories dietitian was also involved. The patient had regular follow-ups, which showed no active issues. The patient was losing weight, and his symptoms of obstructive sleep apnea improved. He started his routine life activities and had a good sleep pattern. He was weaned from antihypertensive medication, and glucose control was optimal without any medication. At the patient’s last visit in March 2018, he had achieved a BMI of 46.4 kg/m2 (147 kg). The only abnormality was that the patient and his wife has been unable to conceive in the four years following his surgery; therefore, an initial workup, including semen analysis, was done. He also complained about a change in the consistency of his semen. Semen analysis showed nil sperm count, and the patient was diagnosed with azoospermia by repeating sample after seven days of sexual abstinence and consultation with a urologist.


The second case was a 48-year-old man who presented to our department with morbid obesity and restricted life activities due to excessive weight gain. The patient’s appetite was normal. The patient had a BMI of 52 kg/m2 (189 kg) with no known co-morbidities. The patient had no addictions and was not taking any medicines regularly. The patient had been married for nine years and had three children with a normal reproductive life and was a lecturer in a university. The patient had a history of follow-up with a nutritionist and a physical trainer, but his weight was not decreasing. Bariatric surgery was decided upon in a multidisciplinary meeting, and the family agreed to the treatment plan. The patient underwent laparoscopic sleeve gastrectomy in 2016. He experienced no immediate complications and he was discharged with multi-vitamins and regular dietitian consultation to meet his caloric requirements. He also attended regular follow-ups. The patient was losing weight successfully and starting daily routine life activities. One year following his bariatric procedure, he had lost 68 kg and achieved a BMI of 41.2 kg/m2; he had also married his second wife. They had not been able to conceive, and he was investigated for infertility, which found no hormonal or reproductive issues. He then underwent semen analysis and repeating sample after 7 days of sexual abstinence it showed azoospermia and a urologist consultation was done (Table ).


A 41-year-old woman with a medical history of hypertension, gastroesophageal reflux, and obesity (BMI: 50.1 kg/m2) was transferred to the emergency department (ED) due to progressive dyspnea and inspiratory stridor over the last three days. The patient showed no dysphagia or dysphonia. A transnasal flexible laryngeal endoscopic examination revealed a right-lateral, subglottic mass (Figures -).
No further laryngeal malformation was detectable. A subsequently performed CT of the neck, thorax, and abdomen demonstrated a 2.2 cm x 1.5 cm sized lesion with well-defined margins located in the right-sided, subglottic larynx with profound stenosis (Myer-Cotton grade III) of the lumen but no extraluminal extension or distant metastases (Figure ).
Tissue samples were obtained by microlaryngoscopy and translaryngeal tracheoscopy in jet ventilation. Histology revealed a moderately cellular myofibroblastic lesion with a noticeable myxoid matrix. The tumor cells had tapering or ovoid nuclei without any atypia or pleomorphism and indistinct palely eosinophilic cytoplasm. Multifocally, prominent osteoclastic giant cells were present, and the myxoid stroma contained scattered chronic inflammatory cells. Immunohistochemistry showed uncharacteristic partial positivity for smooth muscle actin (SMA) and negative staining results for AE1/AE3, desmin, S100, CD34, STAT6, and EMA. The ki-67 proliferative index was 3%. Fluorescence in situ hybridization (Figure ) identified a USP6 (ubiquitin-specific protease 6) gene rearrangement. In summary, the findings fit well with NF.
After tumor debulking and steroid infiltration (triamcinolone; 10%), a regrowth tendency quickly became apparent and due to progressive dyspnea a tracheostomy had to be performed. The patient rejected laryngectomy. After multiple transoral and transstomal tumor resection attempts, postoperative radiotherapy was conducted according to an interdisciplinary tumor and sarcoma board decision to limit regrowth tendency. A conformal photon radiation therapy (6 mV) in the subglottic region was performed with a total of 36.0 gray applicated over 18 sessions. Subsequently, a significant reduction of the tumor volume could be observed after treatment and in the follow-up period. There were sufficient translaryngeal airflow and phonation evident while temporary closure of the tracheostomy, which is why a definite operative closure of the tracheostomy was done 12 months after radiotherapy was completed.
Nevertheless, a discrete stenosis of the subglottic lumen persisted due to the formation of sail-shaped scar tissue in the dorsal (sub)glottic region visible in transnasal flexible laryngeal endoscopic examination, which was not showing any signs of functional limitations in spirometry 16 months after definite therapy (Figure ).


A 63-year-old woman was referred to our center in September 2017, following a 2-year history of progressive asthenia, macroglossia, dysphonia, and significant weight loss. Despite multiple consultations, including a 2014 neurological exam confirming the presence of highly suggestive bilateral carpal tunnel syndrome (CTS), no clear diagnosis was established. Upon admission, she presented with poor general condition, cachexia, ECOG 2, and typical amyloidosis clinical manifestations including dysphonia, hypophonia, dysphagia, macroglossia, submandibular hypertrophy, periorbital hyperpigmentation, autonomic dysfunction with orthostatic hypotension, constipation, paresthesia, and perimalleolar edema. In contrast to general physical wasting, the patient presented with distinct muscular hypertrophy in the lower limbs. Muscle strength was normal, grade 5/5 Medical Research Council, and deep tendon reflexes were slightly diminished.
Further tests were performed to confirm the high clinical suspicion of systemic amyloidosis and to determine the extent of organ involvement. The involved serum free light chain showed a 2000-fold increase compared to the normal maximum value (9310 mg/L), with a high difference between involved and uninvolved serum free light chains (307 mg/L), with immunoparesis, while the bone marrow smear was consistent with a 9% plasma cell infiltration. Fluorescence in situ hybridization for del17p, t(14;16), or t(4;14) was negative. Renal involvement manifested as nephrotic syndrome, with severe proteinuria (9 g/24 h), and mild creatinine clearance decrease (eGFR>50 mL/min/1.73 m2). Although the electrocardiogram and echocardiogram showed no clear amyloidosis-associated changes, NT-proBNP was high (2741 pg/mL), with increased troponin I and troponin T levels. No liver or spleen involvement was observed. Whole-body low-dose CT excluded the presence of osteolytic bone lesions suggestive of multiple myeloma. Abdominal fat pad biopsy confirmed the presence of typical Congo red amyloid deposits with apple-green birefringence under polarized light.
Nerve conduction studies were consistent with bilateral CTS and mild lower limb sensitive polyneuropathy. Needle electromyography described a moderate myopathic pattern in the proximal muscles of the lower limbs, with fibrillation potential.
Subsequently, we confirmed the diagnosis of systemic λAL stage IIIA (European modification of Mayo 2004) with cardiac, renal, soft tissue (musculoskeletal, macroglossia, and CTS) and autonomic nervous system involvement.[
According to existing treatment guidelines for transplant ineligible patients, in September 2017, we initiated the first line of therapy, consisting of bortezomib, cyclophosphamide, and dexamethasone. Despite initial clinical improvement, with partial hematologic (free lambda 1510 mg/L) and renal response (58% reduction of 24H-proteinuria), after 2 cycles of therapy, the patient presented with symptom setback, shortness of breath, accentuated muscular hypertrophy with painful myalgia, fasciculation, and worsening paresthesia. Additional extensive neurological evaluation showed no significant changes compared to baseline, with persistent CTS, mild sensitive polyneuropathy, and electromyographic myopathic changes. Since the cause of the progressive muscular hypertrophy was not entirely clear, an open muscle biopsy of the left vastus lateralis was performed. The initial histopathology report described nonspecific changes, consisting of atrophic and rare hypertrophic fibers associated with mild denervation. Although corticotherapy could have explained the findings, the samples were minutely re-analyzed with additional Congo red staining under polarized light. Surprisingly, apple-green birefringent amyloid deposits, unnoticed on routine staining, were located around the microvessel walls. Immunohistochemical staining revealed sarcolemma hyperexpression of MHC class I. No additional signs of necrosis, mitochondrial abnormalities, fibrosis, rimmed vacuoles, or reducing bodies were observed (Fig. ).
Considering the clinical deterioration, insufficient hematological response, and progressive muscular hypertrophy, now regarded as a direct sign of additional light chain deposition, a second line of therapy was initiated. The new lenalidomide-based regimen (bortezomib, lenalidomide, and dexamethasone) conferred a deepened hematological response (free lambda 516 mg/L) and clinical improvement. After completing 6 bortezomib, lenalidomide, and dexamethasone cycles, the treatment was continued with lenalidomide maintenance. Unfortunately, after just 2 months, she showed symptomatic disease progression, with a significant increase in free lambda chains (969 mg/L), water retention, dyspnea, increased muscle contracture, and dysphagia.
In May 2018, a third line of therapy was initiated, consisting of the second-generation proteasome inhibitor carfilzomib, associated with the lenalidomide backbone (carfilzomib, lenalidomide, dexamethasone). The new regimen led to a complete hematological response, full resolution of muscle pseudohypertrophy, complete renal response (absent 24H-proteinuria), and cardiac response (decrease in NT-proBNP).
During the most recent follow-up, more than 1 year after therapy completion, the patient maintained a deep, durable, and complete hematological response. Clinically, the patient has persistent macroglossia and periocular hyperpigmentation, but remarkably, a complete resolution of muscular and neurological manifestations. Moreover, nerve conduction studies and needle electromyography were within the normal range.


A 45-year-old male presented to the Emergency Department with two episodes of hemoptysis and progressive exertional wheezing over a 9-month period. The patient's past medical history was unremarkable apart from a previous 20 pack-year smoking history. He reported a single episode of hemoptysis 8 years priorly and was lost to follow-up after initial radiologic investigations identified a 3.1 cm mass. He denied any interim respiratory symptoms.
On physical exam, the patient had normal vital signs and was in no apparent distress. His chest exam was normal and there were no stigmata of chronic lung disease. There was no palpable lymphadenopathy. Chest CT imaging revealed a calcified 4.2 cm hilar mass with associated right middle lobe collapse (). The radiologic differential diagnosis included granuloma, carcinoid tumour, or benign nodule. Bronchoscopy confirmed the presence of a highly vascular and obstructive endobronchial mass (). Fine needle aspiration (FNA) of the mass was indeterminate due to low cellularity, despite multiple aspiration attempts. Due to the bronchoscopic appearance, the tumor was presumed to be a carcinoid tumor and so a thoracic surgical opinion was sought for consideration of resection. A right bilobectomy was then undertaken with an intraoperative consultation for preliminary diagnosis and to determine the bronchial resection margin status.
Intraoperative gross specimen assessment revealed a hard, well-circumscribed, ossified 5.0 cm mass () encasing the bronchial resection margin. The firm consistency of the mass precluded conventional tissue sectioning for frozen section evaluation. Cytology scrape smears (Diff Quik, H&E stains) were then prepared from a fleshy endobronchial portion of the mass. The smears contained a uniform population of tumour cells disposed singly and in loosely cohesive groups and rosettes (). The H&E scrape smear preparation confirmed the presence of a stippled “salt and pepper” chromatin pattern, characteristic of low grade neuroendocrine tumours (). A shave section of the bronchial resection margin was negative for malignancy. The preliminary diagnosis at intraoperative consultation was favoured to be carcinoid tumour with the final diagnosis deferred to permanent sections.
Microscopic examination of the formalin-fixed, decalcified mass revealed mature, anastomosing trabecular bone, with intervening nests of uniform tumour cells. The cells were occasionally arranged in trabecular structures and vague rosettes (Figures and ). Despite a prolonged decalcification process, the tumour cells were strongly positive for chromogranin, synaptophysin, and cytokeratin AE1/AE3 immunohistochemistry markers. Necrosis and proliferative activity were absent (Ki-67 index < 1%). Two associated hilar lymph nodes were negative for metastasis. The final pathologic stage was pT2aN0MX.


The patient, a male 46 years old at the time of our visit, underwent surgical resection of nasal pyramid and premaxilla including the whole upper jaw teeth sparing nasal bones. When the patient came to our clinic, apart from the defect resulting from the resection, he presented with a retraction scar crossing the upper lip from the floor of the nasal defect through the filtrum. The surgical resection was performed in another clinic the previous year, and since then, the patient experienced a severe decrease in the quality of social life including the loss of job and falling into reactive depression. The histological aspect of the neoplasia was characterized by high malignancy and contraindicated a microvascular flap reconstruction in order to allow the inspection of the nasal cavity and the facial skin nearby the nasal defect during follow-up appointments.
Furthermore, the conspicuous defect and the different kind of tissues needed would have required multiple donor sites, making the achievement of a good aesthetic and functional result quite challenging. Insofar, due to the entity of the defect, the uncertain outcome of the surgical reconstruction, time-costing evaluation and follow-up need, the patient was proposed to undergo zygoma-implant-supported prosthetic restorations.
Radiographic examination was carried out by means of CT scans of the maxillofacial complex. After the evaluation of the residual maxillary bone, insertion of four zygoma implants was planned.
The surgical intervention was performed under general anaesthesia. Our surgical treatment started with an incision extended from the palatal aspect of the second molar site to the crestal aspect of the canine site bilaterally, with two posterior release incisions. A full-thickness flap was then elevated, and the anterolateral wall of the maxilla was exposed. An oval-shaped window was first drawn and was then opened trough the upper aspect of the maxillary buttress using a large round diamond bur. These windows are used to check the right direction of the zygomatic fixtures during their insertion trough the zygomatic bone. Once the maxillary buttress has been prepared bilaterally, the zygoma implant insertion could start. The preoperative planning provided the insertion of four zygomatic fixtures (Branemark System Zygoma, Zygoma TiUnite® Implant, Nobel Biocare, Goteborg, Sweden), one through the first molar area and one through the lateral canine area on both sides (Fig. ). The reflected mucoperiosteal flap was then sutured with resorbable suture (Polysorb 4.0, Covidien, Mansfield, MA, USA).
Cortical steroids were administered for the first two postoperative days. A postoperative 10-day cycle of antibiotic therapy (amoxicillin 1000 mg TID) was administered. Analgesics were administered as required. Sutures were removed 15 days after surgery. A soft diet was recommended for the first 2 weeks.
Three months afterwards, healing abutments were connected (Fig. ) [].
Approximately 4 weeks after healing abutment connection, intraoral defect including implant abutment and extraoral paranasal defect impressions were taken. The technician managed two different casts: one cast for nasal wax up and one cast for dental wax up. Superior implant bar supported by [] zygoma implants was designed crossing the palatal defect in order to manufacture palatal obturator at a second time. Furthermore, two metal abutments were lodged and fused on the cranial surface of the bar in order to receive epithesis attachments. The abutments acted as primary crowns and secondary crowns, press-fitted on abutments and were used to take an extraoral position impression of the abutments using the nasal wax up as an individual. In this way, the technician could connect OTK (Ball abutment) attachments on the internal surface of the epithesis and thanks to secondary crowns, the nasal prosthesis can be removed for prosthetic aftercare and follow-up inspections. OTK attachments are commonly used because of their retention in overdenture prosthetic rehabilitation. The female part of this peculiar type of ball attachment is made out of Teflon™ (politetrafluoroetilene) while the male part consisted of a titanium structure. A complete implant-supported bar with two bolt prosthesis was made in order to provide superior arch rehabilitation. At the time of delivery, the palatal defect was closed by a soft base material. The nasal epithesis was made of silicone with an acrylic resin internal plate hosting female OTK attachments, whereas male parts were on the secondary crowns.
The patient received an implant-supported intra/extraoral rehabilitation with nasal epithesis and overdenture connected at the same metal framework due to the presence of an oronasal iatrogenic communication (Fig. ). The nasal defect was classified into total (soft and hard tissues) rhinectomy. The palatal defect was localized at the premaxilla and was classified into “good” defect (resection margins into hard palate). Following the delivery of the prostheses, the patient showed satisfaction both for aesthetic and functional results and reverted to normal life achieving social integration (Fig. ); he also reduced anxiolithic and antidepressive drug intake according to psychiatric counselling, and he is waiting to gradually stop them definitively. The patient did not receive radiotherapy and was non-smoker, two factors that are known to influence the success of implant therapy. He started an implant and prosthetic aftercare program.
Patients with advanced orofacial cancer may require extensive surgical resection; the wider and more evident is the amputated region, the more this condition is generating inability for patients []. Visible head site mutilation and functional impairment in speech prevent social reintegration, and abnormal self-perception leads patients to depression [].
Even if modern surgery offers many techniques for reconstruction such as free flaps and rotation flaps, they are not indicated in all clinical cases. Because of the huge number of surgical sessions often required in reaching the wishing result, the use of local or microvascular flap could not be indicated in case of elderly patients or patients affected by cardiovascular or metabolic diseases. Moreover, a multistep surgical planning is not advisable in the absence of a complete sure compliance of the patient to the treatment []. Furthermore, recipient site complication can occur before and after harvesting or radiotherapy, when required, shall compromise the healing of the flap [].
Nowadays, prosthetic extraoral rehabilitation is effective, less invasive because no additional surgical procedure is required, cosmetically satisfying and leads patients to a precocious social reintroduction. Additionally, intraoral restoration such as palatal obturator may allow speech and swallowing which play a crucial role in the retrieval of social life [, ].
Nasal defects are classified into partial, total and extended rhinectomy referred to soft tissue resection, bone and soft tissue amputation and bone and soft tissue associated to the maxilla or orbital excision [].
Extraoral defects are usually restored by means of silicon epithesis; intraoral ones necessitate maxillary rehabilitation. In our case, since the premaxilla was lost, no implant insertion in the anterior region was possible. The importance of anterior implant anchorage is well documented even if a higher failure rate than the ones placed in the posterior maxilla is demonstrated [, , ].
In palatal cleft iatrogenic defects, implants insertion depends on bone residual amount, alveolar ridge height, radiotherapy and peri-implant soft tissue conditions [, ]. In patients who undergone radical surgery, all these requirements are often unfavourable and zygoma implants represent a valid alternative in offering prosthetic anchorage [, , ].
As far as prosthetic design is concerned, it is mandatory to avoid or, if not possible, limit as much as possible distal cantilever: given the absence of the premaxilla, an anterior cantilever is already present. Implant splintage is recommended [, ], and the bar design must respect technical data (implant-to-implant distance, cross-arch stabilization avoiding to cover oronasal communication and shape offering nasal epithesis connection) and clinical requirements (patient’s aftercare, visible inspection for follow-up). One of the most important technical issues is about oronasal communication: if the bar crosses, it is close to the upper lip, no obturator can be manufactured and the lack of vestibular seal may cause nasal flow during beverage swallowing (Fig. ).
The combined zygoma-implant-supported prosthesis and nasal epithesis represents a new approach to rehabilitate wide complex midfacial defects. Nasal reconstruction, oroantral communication closure, labial competence correction and dental prosthetic rehabilitation are not commonly corrected by a unique surgical intervention or by a unique prosthetic rehabilitation. The prosthetic rehabilitation here presented allows to achieve all the above-mentioned goals by means of a single prosthesis.
Intraoral implants offer good anchorage for palatal obturator prosthesis, and extraoral implants’ use to support facial epithesis is well documented. Dawood describes a new implant design to support nasal epithesis and upper jaw prosthesis, but he reports just a single patient treatment []. Bowden reports zygoma implant placement horizontally below orbital floors and nasal prosthesis anchorage, but we managed with combined midfacial and palatal defects [].
Prosthetic aftercare usually requires patient’s instruction about bar and implants’ daily hygienic procedures and silicone nasal epithesis cleaning [, ]. Despite careful home care, silicone facial prosthesis lifespan is 1.5/2 years on average because of discoloration, clip detachment from acrylic to silicone or acrylic carrier detachment to silicone, bad fit or silicone laceration [, ]. Unfavourable events for intraoral prosthesis are screw loosening and bar dislocation or screw fracture, obturator misfitting due to soft tissue remodelling, implant failure and prosthetic teeth fracture or excessive abrasion due to occlusal loss of balance [].
Rethinking globally of the possible indications to the adoption of this technique and its advantages compared to reconstructive microsurgery, the use of zygoma-implant-supported prosthesis may be suitable for patients whose systemic conditions are poor. The duration of surgery and of the postoperative recovery would be remarkably shortened avoiding the complications related to the harvesting of a free flap. Closely related to this aspect, the cost-benefit ratio is definitely more convenient. This technique proves itself to be more easily manageable also in non-compliant patients or in patients with limited prognosis or high risk of recurrence, allowing the clinician a more effective inspection of the resected site during follow-up consults.


A Japanese female patient underwent distal gastrectomy with regional lymph node dissection for gastric cancer when she was 63 years old. The cancer was a poorly differentiated adenocarcinoma with serosa invasion, and lymph node involvement was found. However, no liver tumor was detected during radiological examination at the initial operation. In addition, extensive microscopic examination of the resected stomach revealed no GISTs, with the exception of gastric adenocarcinoma.
Seven years after surgery, an abdominal computed tomography (CT) scan revealed a 6-cm mass in the left lateral segment of the liver, and peripheral enhancement in the arterial phase with a heterogenous appearance (Fig. ). The left portal vein and bile ducts in the lateral segment were not involved. Magnetic resonance imaging (MRI) showed a well-defined mass with hypointensity relative to the liver parenchyma on T1-weighted images (Fig. ) and moderate hyperintensity on T2-weighted images (Fig. ). The bile ducts in the left lateral sector were not dilated. The mass showed hyperintensity on diffusion-weighted images. In the late dynamic and hepatobiliary phases, the hepatic tumor exhibited clear hypointensity on ethoxybenzyl diethylenetriaminepentaacetic acid-MRI. 18F-Fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) was performed to rule out the presence of metastases throughout the body. The hepatic mass showed 18F-FDG uptake with a maximum standardized uptake value of 6.3; however, no other sites of hot 18F-FDG uptake were demonstrated (Fig. ). Upper and lower gastrointestinal endoscopic examinations did not suggest the presence of any other neoplastic lesions. Laboratory findings including levels of serum carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein were within normal limits.
The patient underwent left lateral segmentectomy of the liver because of the possibility of a primary hepatic malignancy. Intraoperative findings indicated that the hepatic tumor was palpable with a hard elastic consistency and had no lymph node involvement; no gastrointestinal tumor was found in the abdominal cavity. The hepatic tumor and the adjacent small intestine adhered firmly to each other, and thus, combined resection was performed. On gross evaluation, the hepatic tumor was well circumscribed and measured 6.8 × 5.5 cm. In cross section, the tumor had a whitish-tan color to the cut surface and focal necrotic and cystic portions (Fig. ). No malignancies were detected in the resected adjacent small intestine.
Microscopically, the hepatic tumor was composed of spindle cells with pleomorphic nuclei arranged into short fascicles. The mitotic count was 35–40 mitoses per 50 high-power fields (HPFs) (Fig. ). Immunohistochemical staining for KIT, CD34, S-100, smooth muscle actin, and desmin was performed. Positive results were observed for KIT and CD34 (Fig. ). The pathological findings indicated the presence of GISTs in the liver. Fletcher’s risk score indicated advanced-stage disease [].
Adjuvant therapy such as imatinib was not administered continuously because of adverse events involving general malaise and anorexia. The patient recovered well from the side effects and exhibited no evidence of recurrence during the 10-month follow-up period.
No other tumors except for the hepatic tumor were identified pre- and intra-operatively in the present case; moreover, no neoplastic lesions were identified after surgical treatment without chemotherapy. We made a final diagnosis of primary hepatic GIST.
GISTs are specific mesenchymal tumors located in regions of the gastrointestinal tract such as in the stomach (60–70 %), small intestine (20–25 %), colon and rectum (5 %), and esophagus (<5 %) []. However, in recent years, GISTs have been reported outside of the gastrointestinal tract as apparent primary tumors. They can also occur in the omentum, mesentery, retroperitoneum, urinary bladder, ureter, uterus, pancreas, and gall bladder [–]. They are designated as EGISTs []. According to Miettinen and Lasota, the frequency of EGISTs is ≤1 % of all GISTs of defined origin []. A PubMed search was performed using the keywords: “gastrointestinal stromal tumors,” “extra-gastrointestinal stromal tumors,” “primary hepatic tumor,” and limited to reports on human adults and English and Japanese-language publications, including case reports. Primary GIST of the liver is a type of EGIST; only eight previous case studies involving this tumor have been reported in the literature until 2015 [–]. The clinicopathological features and treatment outcomes of the reported primary hepatic GISTs, including the present case, are detailed in Table . The patients included six men and three women whose ages ranged from 17 to 79 years (mean, 56 years). There was a distinct predominance of male patients. Four of the nine patients had been asymptomatic, but five had presented with shortness of breath, abdominal fullness, loss of appetite, hypochondriac pain, nausea, and indigestion. The tumors ranged in size from 5.1 to 20 cm with a median size of 9.5 cm. Seven patients had unilobar tumors, and eight patients had solitary tumors in the liver.
All hepatic GISTs demonstrated hypoattenuation on CT scans. MRI was performed for three patients, but no characteristic findings were obtained. 18F-Fluorodeoxyglucose positron emission tomography (18FDG-PET) was performed in three patients, and high accumulation of 18FDG was found in their hepatic tumors. All patients had undergone surgery, with the exception of only one who had been treated with radiofrequency ablation. Morphologically, GISTs can be subdivided into spindle cells, epithelioid cells, and mixed types. Seven of the nine cases were the spindle cell type, one was the epithelioid cell type, and one was the mixed cell type.
The mitotic count in the tumor ranged from 0 to 75 per 50 HPFs, with a median of 20 per 50 HPFs. Fletcher et al. [] proposed a “risk of aggressive behavior” classification of GISTs based only on the tumor size and HPF mitotic count. The risk stratification divides tumors into very low-, low-, intermediate-, and high-risk categories based on size (<2, 2–5, 5–10, and >10 cm) and on the number of mitoses per 50 HPFs, typically reported as <5, 5–10, or >10. The mitotic counts were associated with the recurrence and metastasis of the disease. According to a classification that estimated the risk of aggressive behavior, five of nine cases showed high-risk tumors, including the present case. The histopathological and immunohistochemical characteristics of EGISTs are similar to those of GISTs []. Five cases had high mitotic counts of over 20 per 50 HPFs and, with the exception of the present case, had developed metastases or recurrence.
Four patients had received imatinib chemotherapy, one patient underwent adjuvant therapy, two of three patients with recurrence were effectively treated and remained alive for 36 and 66 months, and the other patient died of the disease. Patients with recurrent tumors could be expected to achieve long-term survival if they had received chemotherapies continuously.
The present case can be considered a primary hepatic GIST because of the following two findings. First, preoperative gastroscopy and colonoscopy imaging studies and extensive pathological examination of the resected stomach failed to detect any other GISTs, except for a hepatic tumor. Second, there was no evidence of recurrence and no neoplastic lesions after hepatectomy in the absence of adjuvant chemotherapy. ICCs are normally present in the myenteric plexus of the gastrointestinal tract, and they have not been identified in the liver. Consequently, is it possible that primary GISTs can occur in the liver? We initially suspected that primary hepatic GISTs might originate from the biliary system in the liver. Ahmadi et al. reported that ICCs were identified in the extrahepatic bile ducts []; unfortunately, the existence of ICCs was not recognized in intrahepatic bile ducts. However, Popescu et al. demonstrated that ICCs are present in human exocrine pancreas; such cells were named pancreatic ICC and later called ICLCs []. Subsequently, ICLCs were identified in many sites such as the following: the upper and lower urinary tracts, blood vessels, pancreas, male and female reproductive tracts, mammary glands, placenta, the heart, and the gut. Recently, ICLCs have been mostly referred to as telocytes (TCs) []. Padhi et al. reviewed 19 reported cases of pancreatic extra-gastrointestinal stromal tumors and concluded that with the discovery and characterization of pancreatic TCs, the origin of stromal tumors reminiscent of GIST seemed a real possibility []. Furthermore, Fu et al. have reported that TCs were identified in the liver and were diminished in liver fibrosis []. Regardless, TCs have not been identified in the normal liver; primary GISTs might have developed from TCs in the liver. Further investigations regarding the relationship between hepatic GISTs and TCs are necessary.


A 68-year-old Chinese male presented to the geriatric ICU in May, 2015, with a “persistent fever lasting two months and worsening shortness of breath lasting one month.” Two months prior to presenting to the ICU, the patient began to experience shivering and hyperpyrexia reaching 40°C and a cough with phlegm production. He denied chest pain and hemoptysis. One month prior to presenting to the ICU, he began to complain of palpitations and edema in his lower extremities. He received antibiotics and diuretics without any progress. Although he was previously diagnosed with chronic bronchitis and pulmonary emphysema many years earlier, PFO and VSD remained untreated. He has been a smoker for 40 years and there is nothing significant in his family history.
Vital signs at time of admission were as follows: temperature 38.8°C, pulse 150 bpm, being conscious and anicteric, no cyanosis, and an operative lymph node palpable in the left iliac region without tenderness. Coarse crackles were heard at the base of lungs bilaterally, as well as cardiac murmurs at the third and fourth intercostal space on the left bounder of the sternum. Moderate pitting edema of both lower extremities was also observed. Laboratory tests were WBC 7.37 × 10E9/l, N 75.8%, Hb 105 g/L, C-reactive protein (CRP) 89.15 mg/L, BNP 523 pg/mL, PCT 0.25, and ESR 95 mm/h. Renal function and liver enzymes were within normal limits. Blood plasmodium test and ANA spectrum were negative. Blood culture was Staphylococcus hominis (sensitive to vancomycin). ECG was paroxysmal supraventricular tachycardia (PSVT) with HR at 155 beats/min. Chest X-ray showed there was some patchy consolidation at the right upper lung and bilateral pleural effusion. The lymph nodes with reactive hyperplasia were detected by ultrasound at bilateral inguinal regions.
Transthoracic echocardiography (TTE) is shown in Figures -.
After his admission, the patient was put on intravenous cefoperazone-tazobactam 2.5 g q12h for 16 days and intravenous Vancomycin 500 thousand q8h for 5 days and then increased to q6h for 11 days. The patient was also put on Propafenone, metoprolol, Perindopril, diuretics, and glyceryl trinitrate. He continued to experience worsening shortness of breath and orthopnea and swelling in his right upper limb, and ECG telemonitoring showed repeated attack of PSVT. The patient was suspected to have developed superior vena cava syndrome; furthermore, the patient received a vascular ultrasound with no thrombosis detected, and BNP reduced to 159 ng/mL. Systemic (18)F-FDG PET/CT scan (Figures and ) revealed that the (18)F-FDG uptake in the mass located in the right atria pathologically increased. The patient finally received lymph node biopsy: large B-cell lymphoma, CD20(+) CD3 T cell(+) Bcl-6(+), CK(+) CD21(−) CD10(−) MUM-1(−) EBER(−). The patient and his family declined chemotherapy and he was discharged from the hospital. He died after 18 days of following up.