A 46-year-old man presented with tingling sensation and numbness on both lower extremities. CT showed hyper-dense masses in both cerebellopontine areas. In the preoperative MR image, a well-defined, lobulated mass with a size of about 5.6 × 2.7 × 6.1 cm is seen in the pons to the medulla area with several internal septae. The mass showed hyper-intensity on T1-weighted, hypo-intensity on T2-weighted, and hypo-intensity on diffusion-weighted images. This lesion shows no gadolinium contrast enhancement. The superior portion of this cystic lesion compressed the lower portion of the pons. The inferior portion of the lesion extended to the posterior and was surrounding the medulla, extending to the C1-C2 intervertebral level (Fig. ). A grossly subtotal surgical resection was done through the minimal lateral supraorbital approach (Fig. ). In the operation field, a shiny multi-lobulated cystic mass was seen on the cerebellopontine angle (Fig ). The trigeminal nerve and seventh and eighth nerves were surrounded by the tumor. The cyst was filled with keratinous debris arranged in laminated layers. On histopathological examination, the cysts were thin-walled and lined by stratified squamous epithelium. Cystic contents included debris and keratin materials (Fig. ). Based on these histopathological characteristics, the patient was diagnosed with an epidermoid cyst. The patient’s postoperative clinical course was uneventful, and neurological symptoms were improved. After the operation, the remnant cystic mass gradually decreased. In 15-month follow-up MR images, the remnant cyst mass completely disappeared (Fig. ).
Epidermoid tumors are rare congenital lesions originating from the ectoderm that constitute 0.3 to 1.8 % of all intracranial neoplasms [, ]. Intracranial epidermoid cysts are considered to arise from epithelial inclusions at the time of neural tube closure or during formation of the secondary cerebral vesicles, and have slow growth rates resembling that of the normal epidermis [].
Pathologically, epidermoid cysts have well-circumscribed, irregular, thin walls with squamous epithelium lining. The epithelium undergoes progressive desquamation and keratin breakdown; therefore, the cystic contents include tissue debris, keratin, water, and solid cholesterol [].
The typical imaging appearance is homogenous non-enhanced hypo-dense on CT, hypo-intense on T1-weighted MR imaging, and hyper-intense on T2-weighted and diffusion-weighted imaging. The CT density of the epidermoid cyst is usually between −2 and +10 Hounsfield units (HU) [, ]. These findings could be attributed to the lipid components and cholesterol. MR signals depend on the relative composition of cholesterol and keratin of the cystic contents. Generally, cholesterol in an epidermoid is in a solid state and appears hypo-intense on T1-weighted images. However, it occasionally presents as hyper-dense lesions on CT, making the diagnosis more difficult. Atypical intracranial epidermoid cysts show a hyper-dense signal on CT and hyper-intense signal on T1-weighted imaging as has been reported [, , ]. The suggested causes of the hyper-intensity on T1-weighted images include high protein concentration, mild calcification, and paramagnetic effects [, ]. According to Ahmadi et al., a protein level of 9.0 g or greater per 100 mL can increase the signal intensity of the cystic fluid on T1-weighted MR images []. Nagashima et al. also examined the total protein concentration of cystic fluid (15 g/dl) and suggested that the highly proteinaceous contents of the cyst contributed to the hyper-density []. The hyper-density could be attributed to the calcification of the keratinized debris and saponification of debris to calcium and also can be attributable to traumatic or spontaneous intracystic microbleeding, abundance of polymorphonuclear leukocytes, and deposition of ferrocalcium complex or iron-containing pigment [, , , ].
The treatment of choice for epidermoid cyst is a total resection of the tumor. But sometimes total resection is impossible because of anatomical complexity. This tumor was fortunately dissected easily from the adjacent structures. But we could not remove all of the tumor because of the long distance from the surgical field, not due to tumor adhesion. So some part of the tumor was left behind at the right upper cervical level. We periodically followed up the patient, and fortunately, the remnant lesion completely disappeared.
The 46-year-old man in our report suffered tingling sensation and numbness on both lower extremities. CT showed hyper-dense masses in both cerebellopontine areas which extended to the C1-C2 intervertebral level. The mass was hyper-intense on T1-weighted and hypo-intense on T2-weighted images.
The cerebellopontine angle is the most common site of the epidermoid tumors, followed by the prepontine, suprasellar, and parasellar cisterns in order. It is less frequently located in the parasellar region and the medial cranial fossa []. To the best of our knowledge, intracranial epidermoid tumors with extension into the upper cervical spinal canal are rare. There are only five such cases reported previously (Table ). Of the five reported cases, only one had atypical hyper-intensity on T1-weighted images and hypo-intensity on T2-weighted images with upper cervical extension. The reason for the unusual downward extension into the upper cervical canal remains unclear. One possibility is that the cistern is anatomically narrower at the lower portion than at the upper portion of the posterior fossa, which would encourage inferior extension. Another possibility is that these tumors tend to spread in the direction of the main flow of the cerebrospinal fluid at the base of the posterior fossa [].


A 32-year-old African American male with a clinical family history of FAP in his mother and 1 of 2 siblings was diagnosed with medulloblastoma at age 10. This was treated with surgical resection followed by RT (54 Gy to posterior fossa, 36 Gy to craniospinal axis; ).
Thirteen years later he underwent near total thyroidectomy. Histopathologic examination revealed multifocal papillary thyroid carcinoma with an insular component involving both lobes. Extensive dense fibrosis precluded total thyroidectomy. The recurrent laryngeal nerve was not visualized, so a posterior portion of the gland was preserved. Five years later, he underwent re-excision of recurrent papillary thyroid carcinoma.
The patient’s family history of FAP prompted screening colonoscopy at age 24, during which 5 sessile polyps were removed from the sigmoid colon. He opted for an extended right hemicolectomy, but after dozens of sessile polyps were found the following year he underwent subsequent total colectomy with ileoanal anastomosis.
At the age of 30, the patient presented with a 1-year history of a painful enlarging right posterior cervicothoracic shoulder mass in the paraspinal trapezius musculature that extended medially to the posterior spinous processes (). Excisional biopsy revealed an 8.3 cm small cell soft tissue osteosarcoma; this was treated with 2 cycles of high-dose methotrexate followed by adriamycin and cisplatin (). Follow-up computed tomography showed residual tumor at the biopsy site. This was re-excised just over a year after the initial biopsy. Histopathologic evaluation demonstrated a 10.5 cm osteosarcoma with 40% tumor necrosis; a positive surgical margin at the trapezius muscle prompted a repeat resection with partial scapulectomy. Six months later, solitary metastatic osteosarcoma was found in the pancreas with subsequent widespread abdominal organ involvement. He underwent additional high-dose methotrexate, adriamycin, and cisplatin therapy, followed by exploratory laparotomy for attempted resection of pancreatic and adrenal masses. Multiple liver and mesenteric masses were found perioperatively and the decision was made not to proceed with surgery. DNA sequence analysis from a blood sample identified a germline heterozygous c.3224delT deletion in exon 15 of the APC gene. This deletion is known to cause a frameshift mutation and accumulation of truncated proteins. Since the heterozygous mutation caused the classic FAP phenotype, this case is consistent with an autosomal dominant inheritance pattern that also fits the positive maternal family history.


A 60-year-old Japanese man presented to Onomichi Municipal Hospital for further investigation of an elevated serum anti-p53 antibody level. The patient had been taking no medications, and he had no history of gastrointestinal diseases. He had been undergoing annual fecal occult blood test and also blood tests which included tests for anti-p53 antibodies and CEA, as routine medical check-ups. Blood tests for anti-p53 antibodies and CEA are optional during an annual health checkup at the patient’s workplace, and these tests were included upon his request. Although his serum anti-p53 antibody level one year previously was 0.0 U/mL, the level had risen to 11.5 U/mL (normal range: 0.0–1.3 U/mL). CEA was within the normal range. A fecal occult blood test performed six months earlier was negative.
The patient had no symptoms. Physical examination revealed no abnormalities, and there was no evidence of an abdominal mass or peripheral lymphadenopathy. Laboratory tests revealed hyperglycaemia and hyperlipidaemia. Colonoscopy demonstrated an ulcerated tumour in the ascending colon (). Moderately differentiated adenocarcinoma was detected in the biopsy specimen taken from the tumour. Computed tomography (CT) scanning of the neck, chest, abdomen, and pelvis revealed a mucosal thickness in the ascending colon, but there were no lymph node swellings or metastatic lesions (). Consequently, the diagnosis of colon cancer, localised in the colon, was made.
The tumour was surgically resected along with peripheral lymph node excision. The postoperative diagnosis was stage II colon cancer. Pathological assessment revealed moderately differentiated tubular adenocarcinoma with subserosal invasion. Metastasis was not detected in the dissected lymph nodes. The patient recovered uneventfully after the surgery. Forty-seven days after the surgery, the serum level of anti-p53 antibody was 14.34 U/mL. The levels had gradually been decreasing, and it finally normalised 21 months after the curative resection ().


A 60-year-old female with no significant past medical history presented with primary hyperparathyroidism. She was asymptomatic with slightly elevated serum calcium and parathyroid hormone (PTH) levels. The sestamibi scan did not show any uptake, while the computed tomographic scan (CT) of the neck showed an incidental right paraesophageal air-filled diverticulum with multiple thin septations (). During surgery, three and a half parathyroid glands were explored and resected resulting in the drop of blood PTH level, confirming the diagnosis of parathyroid hyperplasia. In addition, a cystic structure densely adherent to the trachea was found in the right tracheoesophageal groove. Blunt dissection was performed around this mass without difficulty, though tissue planes between the mass and the trachea could not be readily separated. Sharp dissection was then performed to complete the resection off the tracheal wall over the small surface area to which it seemed attached. There did not appear to be any apparent lesion left attached to the trachea and there was no tracheal injury or entry point noted at this time. The specimen was sent for intraoperative assessment, which revealed several lumina/cystic spaces lined by ciliated columnar epithelium with mild lymphocytic infiltrate and salivary-type glands in the adjacent fibrous tissue. Given the absence of apparent tracheal entry point, no formal repair of the trachea was undertaken, though the patient was monitored postoperatively for any signs of tracheal communication. In the absence of detailed clinical information, based on these histologic findings, a tracheal diverticulum, laryngocele, or bronchogenic cyst was favored. Lymphoepithelial cyst and branchial cleft cyst were also considered in the differential diagnosis.
The specimen submitted for pathologic examination consisted of a 2.4 × 1.5 × 0.8 cm tan brown multiloculated/cystic structure with some attached adipose tissue. The cyst wall measured 0.1 cm in thickness. An opening of 0.2 cm in diameter was noted on one aspect of the lesion ().
Histologic examination of the entire lesion confirmed the presence of cystic spaces lined by respiratory-type ciliated columnar epithelium, minor salivary gland tissue, and lymphoid aggregates (Figures and ). Given the morphologic, imaging, and operative findings, the diagnosis of tracheal diverticulum was rendered. Branchial cleft cyst and bronchogenic cyst were also considered in the differential diagnosis but were not favored for reasons mentioned in the discussion.


A 41-year-old man first visited the urologist in a general hospital because of gynaecomasty and a mass in the right groin 6 years ago. He had a history of a left-sided orchidectomy as a baby, and a surgical correction of a right-sided inguinal hernia at the age of 31. Because of an abnormal ultrasound of the right testicle and increased tumour markers in the blood, a radical inguinal right-sided funiculo-orchidectomy was performed, and a testicular prosthesis was placed. The resection specimen showed a non-seminomatous testicular cancer, which consisted purely of embryonic cell carcinoma without components of teratoma. The contrast-enhanced CT of the thorax and abdomen performed the day after the orchidectomy showed extensive abdominal lymph node metastases, multiple liver metastases, metastases in the left adrenal gland and metastases in the right inguinal region.
Because of this poor-risk non-seminomatous testicular cancer, the patient was referred to the Oncology Department of our University Medical Centre. Initial serum markers were: lactate dehydrogenase (LDH) 1,534 U/l (normal, <250 U/l), beta-human chorionic gonadotropin (beta-HCG) 17.5 ng/ml (normal, <1.0 ng/ml) and alpha-fetoprotein (AFP) 527 μg/l (normal, <3.0 μg/l). Chemotherapy with bleomycin, etoposide and cisplatin (BEP) was started immediately. The patient tolerated the four cycles of chemotherapy relatively well. Within 2 months after the start of chemotherapy, the serum tumour markers normalised. However, contrast-enhanced CT after completion of the chemotherapy showed a mixed response: the lesion in the left adrenal gland and the abdominal lymph node metastases had declined, but the lesions in the liver and the right inguinal region showed an increase in size (Fig. ). Because of the normal serum tumour markers and the radiological aspects of these growing lesions, growing teratoma was suspected. Biopsy of one of the liver lesions showed no malignancy. Whilst planning extensive surgery for the suspected teratoma lesions in the liver, the patient unfortunately presented with a biochemical relapse (AFP, 47.1 μg/l) of his non-seminomatous testicular cancer and a deterioration of his renal function due to obstruction of the right ureter by a tumour mass. The surgery was postponed and a double-J catheter was inserted in the obstructed right ureter, after which the renal function normalised. To evaluate the extent of the disease, FDG-PET/CT was performed, which showed multiple small liver lesions with a high metabolic activity and two highly metabolic active regions in the right inguinal mass, all suspected to be metabolically active malignant tumour. FDG-PET/CT also showed two large liver lesions without increased FDG uptake, probably teratomas. Because of the recurrent non-seminomatous testicular cancer, the patient was treated with four cycles of second line chemotherapy consisting of paclitaxel, ifosfamide and cisplatin (TIP). The serum tumour markers normalised and follow-up FDG-PET/CT performed after two cycles of chemotherapy showed a complete metabolic response in all lesions.
However, a further FDG-PET/CT performed after completion of the four cycles of chemotherapy showed new, highly metabolically active lymph nodes in the retro peritoneum again suggestive for viable tumour, whilst the serum tumour markers remained normal. The patient underwent a retroperitoneal lymph node dissection, including resection of these FDG avid regions, which showed mature teratoma with secondary malignant components of papillary carcinoma and astrocytoma grade II (Fig. ).
A few months later, a follow-up FDG-PET/CT showed increasing metabolic activity in the right inguinal mass and in a liver lesion. First, a right sided inguinal lymph node dissection was done, which showed teratoma with a neuroglial component of uncertain malignant potency (Fig. ). Subsequently, a partial resection of the liver was performed, which showed teratoma with the same known neuroglial component and a lesion with secondary malignant degeneration, possibly gliosarcoma or pleomorphic malignant fibrous histiocytoma (Fig. ).
After surgery, the patient was in excellent health and remained free of disease for more than a year. However, during follow-up, FDG-PET/CT showed a hypermetabolic tumour in the musculature of the right upper leg. To rule out metastases, this lesion was excised, and it appeared to be a nodular fasciitis on pathological examination.
The first follow-up FDG-PET/CT, 2 months after resection of the nodular fasciitis, showed increasing metabolic activity in one of the teratomas in the liver and in the postsurgical region in the liver. Again, the affected segments were excised, which showed mature teratoma with secondary malignant degeneration with neuroglial and probably mesenchymal components.
At present, the patient is 6 years after his primary diagnosis of poor risk non-seminomatous testicular cancer with secondary somatic malignant dedifferentiated mature teratoma. The last surgery is now more than 3 years ago. The patient remains in an excellent clinical condition, is working full time, plays water polo and has no evidence of disease, neither biochemically nor on multimodality imaging with FDG-PET/CT.


An 80-year-old male was admitted to our hospital after he found a painless mass in the upper inner quadrant of his left breast. The patient had no history of breast injury or systemic disease except hypertension. His physical examination disclosed a nontender, hard, mobile mass with regular contour in the upper inner quadrant of the left breast. Axillary lymph nodes were not palpable and the overlying skin showed no retraction.
The patient was initially evaluated by mammography (MG). The MG showed a 3.0 × 2.0 cm well-defined, round-shaped, medium-density mass in the upper portion of the left breast but no associated calcifications or architectural distortion () nor gynecomastia. After the MG evaluations, the lesion was evaluated by ultrasonography (US) examination, which showed a well-defined homogeneous hypoechoic solid mass of the left breast. No acoustic shadowing or increase through transmission was apparent.
The patient next underwent bilateral dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and diffusion weighted imaging (DWI) via a 1.5 Tesla MR. Kinetic and morphologic analyses were performed on DCE-MRI. The lesion was oval, with a circumscribed margin. The signal intensity of the mass showed hypointense on precontrast T1-weighted MR () and hyperintense on T2-weighted images (). Gd-enhanced fat-suppressed T1-weighted MR images showed early strong enhancement of the mass with nonenhancing internal septations (). Apparent diffusion coefficient (ADC) maps were used for ADC measurements. The lesion ADC value was 2.280 × 10−3 mm2/s ().
For staging of malignant lesions, F18-fluoro-2-deoxyglucose positron emission tomography (FDG/PET) was performed to the patient, who had been prediagnosed with breast cancer. In the upper-left inner quadrant of his breast a round-shaped, nodular lesion was detected with a 12 mm diameter and a hypodense center with low FDG uptake (SUV max: 1.2) ().
US-guided core needle biopsy of the mass from the breast was performed for histologic examination and exact diagnosis. The pathological results of the core biopsy were inadequate for differentiating between invasive carcinoma and a benign lesion. Therefore surgical excision was performed.
The lesion was composed of a well-circumscribed but not encapsulated proliferation of round, epithelioid-shaped myofibroblastic cells configured in single file or as small clusters in a vascularized, weakly collagenized stroma. Its histologic appearance resembled an invasive lobular carcinoma (). Immunohistochemistry revealed that the tumor cells were negative for keratin () but positive for antismooth muscle actin and estrogen receptor (). These findings are characteristic of epithelioid myofibroblastoma.


63-year-old woman applied to hospital in July 2012 with bruises on chest without trauma. In her anamnesis, it was learned that she also had large bruises after trauma before the admission. In her physical examination spleen was palpable under arcus costa. Her laboratory tests results were hemoglobin 13.6 gr/dL, white blood cell 8.2 × 103/μL, and platelet 600 × 103/μL. There was no cause for reactive thrombocytosis and serum iron levels were normal. Hematocrit level was 37%. In detailed tests Philadelphia chromosome was absent and JAK2 mutation was positive. She was diagnosed as having essential thrombocytosis and she was given hydroxycarbamide treatment with a dose of 2 × 500 mg/day. There were no complications and she was on periodic follow-up by our clinic. However in July 2014 she started to feel pain in her toes. Clinical examination revealed melanonychia on her upper and lower extremity nails (Figures and ). Hydroxycarbamide treatment was discontinued because of pain and she was given Anagrelide treatment. Anagrelide was well tolerated and our patient is still on clinical follow-up with this treatment without complication.


Thirty-year-old male patient, who followed with a diagnosis of β-thalassemia major, was admitted to the emergency room with palpitations and chest tightness before half an hour. There was a history of blood cell transfusion for thalassemia since the age, 8 years old began to deferoxamine, 10-year-old splenectomy was performed and before 4 months was started deferiprone in addition to deferoxamine. There was increase in dyspnea and palpitation in the past few months. During the application, blood pressure was 90/50 mm Hg, the pulse 176/minute, an electrocardiogram showed wide-complex tachycardia (Fig. ). The patient initially received intravenous amiodarone (300 mg/30 min) and transfered to coronary intensive-care unit. 15th minute of infusion, the patient became hypotensive and hemodynamically unstable, lost consciousness, pulseless ventricular tachycardia (VT) were defibrillated with 200 joules and sinus rhythm was achieved (Fig. ). Then installation of intravenous amiodarone was completed and the maintenance of oral treatment was passed, metoprolol 50 mg/day and ramipril 2.5 mg/day was administered. Transthoracic echocardiography revealed normal left ventricular systolic function, left ventricular hypertrophy and diastolic dysfunction have a restrictive filling pattern (Figs. , , and ). The hemogram reveals profound anemia with a hemoglobin level of 8.4 g/dL, diluted ferritin was 1300 ng/mL, thyroid hormones, electrolyte levels and cardiac enzymes were normal. Erythrocyte suspension were given the suggestion of hematology clinic, chelation therapy was continued. The patient was taken to control ventricular arrhythmias with amiodarone, ICD implantation was performed for the purpose of secondary prevention. Patient's ECG, has viewed repolarization changes during follow-up (Fig. ). Follow-up of patient without complication and was discharged with metoprolol and amiodarone therapy.


A 22-year-old gravida 2, para 1, living 1 woman presented to obstetrics polyclinic for her first obstetric visit. She had a history of nonconsanguineous marriage. She had no history of iron and folic acid supplementation. Her routine blood and biochemical tests were within normal limits. Abdominal examination revealed a uterus of 16-week size. Serum alpha-fetoprotein was significantly raised. Ultrasound revealed an 18-week, single-live fetus with severely hyperextended head and strikingly short vertebral column with no apparent fetal neck. The family was counseled and offered termination of the pregnancy. After rejecting termination, they were offered an amniocentesis, which they also rejected. The woman did not continue her routine visits. At 32 weeks of gestation, she was admitted with rupture of membranes and contractions. Ultrasonography revealed a live fetus with hydrocephaly and iniencephaly. Since biparietal diameter of the fetus was above 100 mm and the mother had a previous C-section, she underwent cesarean delivery. A 1350 gr female fetus with fixed retroflexion of the head, without a neck, and with low-set ears () and lumbar meningocele () was dead at 10 minutes after birth. Since the family did not accept autopsy, further evaluation for the presence of additional anomalies was impossible.


Patient 1 was a 19-year-old right-handed female. She was undergoing cognitive behavioral psychotherapy for 3 weeks during the measurements, and was not using psychotropic medication.
According to SCID-I interview, Patient 1 met the criteria for OCD with predominantly compulsive behavior. The Y-BOCs score also indicated mild OCD symptoms at the pre-test and the post-test. The BDI-II indicated severe depression. In comparison to healthy subjects, the patient suffered from higher anxiety levels according to the STAI trait.
Patient’s pre-post questionnaire results are presented in .


Patient 2 was a 25 years old right handed female. She was an in-patient, underwent cognitive behavioral psychotherapy for 3 weeks before the measurements and was using psychotropic medication (Setralin 150 mg).
Patient 2 met SCID-I criteria for OCD predominantly with compulsive behavior, and had a low severity of symtomatology according to Y-BOCs. No clinically significant depression or anxiety was detected.
The patient’s pre-post clinical results are presented in .


The third patient was a 26-year old left handed male. He was under psychotropic medication (Setralin 125 mg., Risperdal 0.5 mg.), but not undergoing psychotherapy during the measurements. This patient received 4 days of rtfMRI-neurofeedback training.
Patient 3 met criteria for OCD and major depression in accordance with BDI-II. A decrease in the Y-BOCs score was observed after training. Patient 3 showed high levels of anxiety before and during the experiments. Patient’s pre-post questionnaire results are presented in .


We report a case of axillary lymphadenopathy in a 61-year-old Egyptian man who presented to our cancer clinic at Mansoura Oncology Centre with a recurrent PTC. He had a history of total thyroidectomy and right radical neck dissection 18 months ago, which were followed by two doses of radioactive iodine at intervals of 6 and 12 months.
On clinical examination, there was a recurrent mass at the right lower parotid region, left cervical and axillary lymphadenopathy.
Imaging was performed in the form of a computed tomography (CT) scan of his neck, chest and abdomen which showed: 1) multiple bilateral cervical lymphadenopathies of which the largest node was 2.5cm in diameter at level III, 2) right intraparotid lesion 2.5×3.5cm in diameter, and 3) left axillary lymph nodes of which the largest node was 3cm in diameter (Fig. ).
Fine-needle aspiration from his left cervical lymph nodes as well as from his left axillary lymph node revealed metastatic PTC.
He was managed by removal of the recurrent right intraparotid mass, left comprehensive neck dissection and left axillary dissection (Fig. ).
Postoperative pathology revealed recurrent papillary cancer at the right intraparotid mass, infiltration of 10 lymph nodes out of 16 lymph nodes of the left neck dissection and infiltration of one lymph node out of 11 lymph nodes in axilla by PTC (Fig. ).
He had an excellent recovery without complications (Fig. ).


A 6-year-old white boy was diagnosed to have a large aortopulmonary collateral artery during preoperative evaluation for adenoidectomy. He had a history of recurrent respiratory tract infection, symptoms of gastroesophageal reflux and scoliosis. Saturation was normal and no abnormal auscultation findings were noted. His weight was 20.7kg (25–50 percentile) and height 119cm (75 percentile).
Prenatal exposure to carbamazepine because of maternal epilepsy was reported. He was delivered at term (birth weight 3100g). He underwent ventricular and atrial septal defects correction in the perinatal period. Since birth facial malformations (long philtrum, micrognathia, epicanthic fold) and paralysis of facial muscles resulting from dysfunction of the seventh cranial nerve were documented. DiGeorge syndrome and array-CGH deletions were excluded.
On chest X-ray were signs of bronchitis and hyperperfusion of his right lung (Fig. ). An echocardiogram showed no shunts and no evidence of ventricular overload. A computed tomography (CT) angiography scan revealed an abnormal vessel arising from the thoracic descending aorta coursing toward his right upper lung. On endovascular occlusion, the angiogram confirmed the hyperperfusion of the right upper lobe (Fig. ). The diameter of the aberrant vessel was up to 8mm. No lung anomaly or other abnormal vessels were detected. Three-dimensional volume rendering of the malformation is shown in Fig. .
Pulmonary hyperperfusion is a risk factor for recurrent cardiorespiratory infection and lung hypertension. This risk is probably higher in syndromic malformations. A mini-invasive vascular occlusion was attempted after a multidisciplinary evaluation (pediatric cardiologist, pediatrician, pediatric surgeon and interventional radiologist).
Under general anesthesia, ultrasound-guided right femoral common artery access was gained. The major aortopulmonary collateral artery (MAPCA) was easily catheterized with a 4F vertebral Glidecath catheter. The hypertrophied pulmonary arteries of the superior lobe were opacified as well as the normal venous drainage excluding a lobar sequestration. Due to the very short length and ascending direction of MAPCA, coils as embolic agents were excluded because of the high risk of nontarget embolization. Through the Glidecath a 6mm bi-segmentary Amplatzer plug type IV was released but it appeared undersized and unstable. The plug was withdrawn from the outer portion. The Glidecath 4F was exchanged over a stiff wire with a 4F 55cm-long Cook sheath with its distal tip in the pulmonary tree. A new tree segments (or lobes) 8mm Amplatzer plug type II was released through the sheath inside the MAPCA. At completion angiography through the side arm of the sheath the MAPCA was embolized (Fig. ). Hemostasis was done at the femoral entry by manual compression.
A chest radiogram and CT showed normalization of the vascular pattern of the right lung at 9-months follow-up (Fig. ).
No complications and no respiratory infections in the first follow-up year were observed. A good growth gain was observed: weight 25kg, 75 percentile; height 121cm, 75 percentile.


A 69-year-old woman was referred to our institute for further evaluation of a tongue mass. She had a 5-year history of pain involving the right lateral tongue edge, and the lesion had been diagnosed as lichen planus by incisional biopsy performed by her dentist. The disease was stable for a long time; however, the tongue pain suddenly worsened. Physical examination revealed an elastic, hard, 1.2 × 0.7 cm mass of the right tongue (Fig. ). There was no palpable lymphadenopathy in the head and neck area. The patient was being medically treated for hypertension and diabetes mellitus, both of which were well controlled. She denied using tobacco or alcohol but had been exposed to smoke from her family. She had no history of exposure to ionizing radiation or having undergone cancer chemotherapy. Regarding her family history, her younger brother had been treated for rectal cancer and liver metastasis.
Contrast-enhanced CT scans of the head and neck, chest, and liver were performed as a routine procedure in patients with oral cavity cancer. CT showed no lesions in the tongue, cervical lymph nodes, lungs, bone, or liver; however, three masses were detected in both breasts and the right kidney. Whole-body FDG-PET was performed to identify any other lesions; no other lesions were found. An upper gastrointestinal examination, indirect laryngoscopic examination, and bone scintigraphy revealed no abnormalities. The patient had no breast- or kidney-related signs or symptoms before we identified the masses. Fine-needle aspiration cytology was performed to confirm the diagnosis of the bilateral breast masses and revealed malignancy on both sides. Renal cancer was suspected based on the CT findings (Fig. , arrow). All four lesions were diagnosed as early-stage cancers at the initial presentation.
We removed the four tumors over three surgical procedures because the patient had diabetes mellitus. The patient underwent wide local excision of the tongue tumor. Histopathological examination revealed a moderately differentiated SCC. The bilateral breast lesions were then resected, and histopathological examination revealed an invasive ductal carcinoma (positive for estrogen receptor and human epidermal growth factor receptor 2, negative for progesterone receptor and MIB-1; 7–8 %) of the right breast representing a scirrhous growth with one metastatic axillary lymph node. An intraductal carcinoma of the left breast (MIB-1, 7–8 %) was also found. After resection of these lesions, laparoscopically assisted partial resection of the right kidney tumor was performed. Histopathological examination revealed a chromophobe RCC with positive cytoplasmic Hale’s colloidal iron staining. Immunohistochemistry, cytokeratin 7, CD10, and E-cadherin were positive.
In summary, we resected four synchronous MPCs including a moderately differentiated SCC of the mobile tongue, invasive ductal carcinoma of the right breast, intraductal carcinoma of the left breast, and chromophobe RCC of the right kidney. The patient received adjuvant therapy (radiation therapy and anastrozole) for both breast cancers. After a 5-year follow-up period, the patient was alive and well with no clinical or radiologic signs of recurrent or metastatic disease.
This case illustrates two important clinical issues. This combination of MPCs, namely that involving the tongue, bilateral breasts, and kidney, has not been reported to date. To avoid overlooking kidney MPC, we suggest that contrast-enhanced CT should cover an extended region ranging from the liver to the inferior margin of the kidney in patients with oral cavity cancer.
First, regarding the fact that this combination of MPCs has not been reported to date, we searched PubMed and the Japan Medical Abstracts Society databases but found no case reports of the same combination of cancers. The current case was defined as MPCs according to the Warren and Gates criteria []; namely, each cancer must be distinct, and the probability of one being a metastasis of the other must be excluded. Using this definition, all four neoplasms were determined to be primary cancers. Furthermore, we defined these cancers as synchronous cancers based on Moertel’s definition; that is, a primary tumor recognized within or after 6 months of diagnosis of another primary tumor is defined as synchronous or metachronous, respectively []. We thus diagnosed the present case as synchronous quadruple MPCs. We believe that the patient had three risk factors that contributed to this combination of MPCs. First, the patient had a previous diagnosis of diabetes mellitus, which may increase the risk of cancer [, ]. Second, the patient’s family members were chronic, heavy cigarette smokers []. Third, the patient’s younger brother had colon cancer []. Synchronous quadruple MPCs are extremely rare, and all such cancers can be found in the early stage. MPCs in patients with oral cavity cancer mainly occur in the HNLE region []. In contrast, the incidence of non-HNLE cancer, including cancer of the kidney or breast, is relatively low in patients with oral cavity cancer []. The 1973–2000 SEER Cancer Registries indicates that of 26,984 patients with oral cavity cancer, the rate of second primary kidney cancer and breast cancer occurring within 1 year after oral cavity cancer diagnosis was only about 0.03 and 0.11 %, respectively []. There are few reports of oral-cavity–kidney combinations of MPCs [, , , ]. We found no other English-language literature describing synchronous MPCs as oral-cavity–kidney combinations [, –].
The second important clinical issue illustrated by this case report is that contrast-enhanced CT should cover an extended region ranging from the liver to the inferior margin of the kidney in patients with oral cavity cancer to avoid overlooking kidney MPC. We usually perform neck, chest, and liver CT scans to detect MPCs or distant metastases in patients with oral cavity cancer. In these cases, we must evaluate the MPCs or distant metastases with nothing but contrast-enhanced CT. We performed a liver CT scan containing the kidneys and incidentally noticed an early-stage mass of the right kidney. In patients with oral cavity cancer, the probability of detecting kidney cancer is low according to the 1973–2000 SEER Cancer Registries []. However, recent reports have indicated that the lifetime risk for developing kidney cancer is about 1.6 % [] and that the incidence of RCC has continued to increase []. Furthermore, early-stage RCC can remain clinically silent for a long time, and the clinical symptomatology is generally expressed in patients with advanced disease []. Advanced or metastatic RCC is associated with a much lower 5-year disease-specific survival rate than is early-stage RCC []. According to the lack of symptoms and the invisibility with FDG-PET, hidden synchronous renal cancer in patients with oral cavity cancer may be much more frequently present than previously thought. Therefore, clinicians should detect the kidney cancer in the early stage using an extended CT scan with consideration of both the benefits and risks, the latter of which include high cost and radiation exposure. The risk of development of secondary kidney or breast cancer after oral cavity cancer is not particularly higher than the risk of after other HNLE or skin (non-melanoma) cancers [, –]. Therefore, in patients with not only oral cavity cancers but also other HNLE or skin cancers, hidden kidney cancer may be detected by CT covering an extended region ranging from each routine region to the inferior margin of the kidney.
In general, the performance of several types of examinations can help to prevent overlooking synchronous MPCs. FDG-PET is usually used to identify synchronous MPCs; however, FDG-PET sometimes identifies false-positive lesions. In the current case, we could not detect the kidney mass by FDG-PET. The application of FDG-PET to the urinary tract is relatively limited because this tract is the major excretion route for FDG, and background activity may thus obscure the presence of lesions []. Additionally, FDG-PET is generally expensive; therefore, some patients with oral cavity cancer are denied this examination before cancer therapy.


22-year-old male patient from Turkey, who was a wrestler, applied to the Emergency Service with joint open dislocation in finger due to a ball hitting his extension in his right hand, while he was playing football as a goalkeeper without gloves in an astro pitch. He had a proximal interphalangeal joint dislocation injury in his hand in the 4th finger in radial side stretching to the proximal phalanx and accompanied by nearly 1,5 centimeters laceration (Figures , , and ). There was no neurovascular deficit in the finger of the patient. Washing and debridement were applied to the open joint of the patient. There was damage in the volar plate and in radial side collateral ligament. The volar plate and collateral bond fixation were applied with absorbable 5-0 PDS (PDS, Ethicon, San Angelo, TX, USA) sutures and with no need for periosteum pull-out sutures with the modified Kessler suture technique. After the reduction, the patient was kindly taken to the PIP joint extension application and the joint stability and neurovascular examinations were performed. Postoperative proximal interphalangeal joint was stable and to prevent joint from Kirschner wire traumas, Kirschner wire fixation was not implemented (Figures and ). Dorsal aluminum split was applied to the patient in postoperative 30 degrees flexion. The patient was given a postoperative antibiotherapy and wound area was examined. In the 4th week he was taken to the physical treatment program. At the end of the 6th month, the patient was able to start his active sport life fully again. Finger's flexion and extention range of motion was full degrees (). However there was no stiffness, pain, or chronic instability. In addition, postoperative scarring was minimal.


A 23-year-old female with a past medical history of depression, borderline personality disorder, obsessive compulsive disorder, psychosis NOS, and congenital hydrocephalus with VP shunt presents following ingestion of approximately 40 g of HCQ. She had been using HCQ for the treatment of pruritus. She was also being treated with risperidone, clonazepam, and zopiclone for her psychiatric disorder and fluconazole at the time of presentation for the treatment of a vaginal yeast infection. At presentation, she had a Glasgow Coma Score (GCS): 15/15, temperature: 37.1°C, blood pressure (BP): 92/60 mmHg, pulse rate: 65/min, respiratory rate: 16/min, blood glucose: 3.9 mmol/L, and serum potassium: 3.0 mmol/L. The initial blood gas demonstrated a metabolic acidosis and respiratory alkalosis: pH: 7.33, pCO2: 16, pO2: 70, and bicarbonate: 8. Electrocardiograph performed on arrival demonstrated sinus rhythm with a widened QRS (140 ms) and QT interval (QTc 576 ms). See . Her urine toxicology was negative for salicylates, ethanol, acetaminophen, benzodiazepines, cannabinoid, cocaine, opiates, and amphetamines. The presenting renal and hepatic laboratory values are as follows: creatinine (Cr): 133 μmol/L; albumin: 39 g/L; lipase: 113 units/L; gamma-glutamyl transpeptidase (GGT): 30 units/L; alkaline phosphatase: 55 units/L; total bilirubin: 3 μmol/L; direct bilirubin: 1 μmol/L; alanine aminotransferase (ALT): 23 units/L; aspartate aminotransferase (AST): 14 units/L.
Within three hours of her overdose, the patient became obtunded requiring intubation and mechanical ventilation. Hypotension was treated with crystalloid and vasopressor support. Gastric lavage and activated charcoal for decontamination were provided. Within six hours of her overdose, she demonstrated severe hemodynamic instability resulting from myocardial irritability with frequent ventricular ectopic activity leading to runs of polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) requiring 18 defibrillations with 200J with biphasic defibrillator over the first 18 hours after ingestion. Given her protracted cardiac instability, additional treatments including intravenous diazepam 60 mg followed by infusion of 6 mg/hr for calcium channel stabilization (total of 82 mg given), epinephrine 20 mcg/min, norepinephrine 30 mcg/min, sodium bicarbonate 30 mmol/hr, and magnesium sulfate 1 g/hr infusions were also initiated. The serum potassium three hours after the overdose was 1.5 mmol/L. In total, 380 mmol of potassium chloride was given over the first 18 hours administered in 20 mmol boluses. She also received intravenous sodium bicarbonate for alkalization. To treat refractory ventricular ectopy, a bolus dose of 1.5 mL/kg of 20% Intralipid ILE was initially given followed by a high dose infusion over approximately 30 minutes. A total of 500 mL of ILE was given. No further infusion of ILE was given after this initial dose. Vascular access for dialysis was established immediately after the bolus dose and thus dialysis overlapped briefly with the infusion of ILE. The runs of PMVT and VF were felt to be secondary to a preexisting channelopathy likely potentiated by fluconazole and risperidone. Ventricular pacing was reviewed but not considered indicated. The patient was started on piperacillin/tazobactam for possible aspiration pneumonia. Echocardiographic imaging revealed normal global ventricular contractility with an ejection fraction of 60%.
The patient was started on intermittent hemodialysis (IHD) in an attempt to reduce HCQ levels despite a paucity of literature regarding its use. The pharmacokinetics suggests that much of the drug is not accessible to the dialyzer, but given the severity of the overdose and the impact of hemodynamics even a small amount removed was considered favorable. Plasma HCQ level was 6425 mol/L 12 hours after ingestion. A five-hour run of hemodialysis was initiated with end points being either improved hemodynamics or of significant decrease in blood levels. A F1000 Dialyzer was used with a dialysate flow rate of 800 cc/hr. In total, 135 L of blood was processed. As noted above, concurrent with the dialysis run, an ILE infusion was administered in an effort to create a “lipid sink” to sequester lipophilic HCQ. At 31 hours after ingestion, the plasma HCQ level was 4328 mol/L.
Improvements in her hemodynamics were observed after administration of dialysis and ILE. She was subsequently weaned from the ventilator and extubated on day 3 and discharged from ICU on postadmission day six.


A 57-year-old female patient presented on day 3 after ingestion of approximately 200 g of self-collected mushrooms with a history of severe gastroenteritis beginning on day 1 and lasting through admission. On the day of admission, she became increasingly weak, providing her with the reason to seek medical attention. Otherwise, the patient had no medical record of any significance. The patient presented with stable cardiovascular and pulmonary function, afebrile, with diffuse abdominal tenderness and lively bowel sounds. There were no mushroom residues available for examination by an expert, but Amanita phalloides intoxication, which was highly compatible with the description of the patient and the clinical course, was proven via detection of α-amanitin in the urine using ELISA (Buehlmann Laboratories, Schonenbuch, Switzerland) with a maximal concentration of 42.2 μg/L on admission on day 3. Directly on admission, intravenous silibinin (Legalon SIL, Rottapharm, Monza, Italy) and acetylcysteine (Fluimucil 10%, Zambon Pharma, Milan, Italy) and multiple dose oral activated charcoal therapy were initiated at the intensive care unit according to current guidelines []. Silibinin was administered intravenously at 20 mg/kg per day for three days after a loading dose of 5 mg/kg; acetylcysteine was administered intravenously at 150 mg/kg over 1 hour, followed by 12.5 mg/kg over 4 hours and 6.25 mg/kg over 16 hours. At admission on day 3, liver enzymes were already elevated, reaching maximum on day 4 with alanine aminotransferase levels of 6894 U/L, aspartate aminotransferase of 5232 U/L, and lactate dehydrogenase of 10596 U/L. Alkaline phosphatase and γ-glutamyl transferase levels remained normal. As a measure of liver function, factor V activity was nondetectable on day 4, with factor II activity at 29% (60–150) and factor VII activity at 25% (60–150); the international normalized ratio (INR) was 2.7. Fortunately, liver function improved without further interventions on day 7 (). The patient initially also presented with renal failure. Renal ultrasonography studies were normal; however a calculated fractional excretion of urea of 65% hinted at an intrarenal pathology. Renal failure was completely reversible by day 4 without need for renal replacement therapy. On day 8, however, the patient developed severe abdominal pain, tenderness on examination with signs of peritonitis especially in the lower right quadrant, accompanied by watery diarrhea and an elevation of inflammatory parameters. Cardiovascular and pulmonary function remained stable. Abdominal computed tomography showed a thickening of the bowel wall of the entire ileum and no other pathologies. On day 12 after mushroom ingestion gastrointestinal biopsies were taken from the ileum and the large bowel; see Figures and . Diagnostic findings were most prominent in the mucosa of the ileum and the cecum and decreased towards the rectum. The mucosa of the ileum showed, in addition to acute cryptitis and ulcerating inflammation with fibrinoleukocytic exudate (pseudomembranes), regenerating changes of the epithelium. Acute erosive and ulcerating inflammatory changes together with a rarefication and atrophy of crypts, fibrosis of the lamina propria, and regenerating epithelial changes were most prominent in the cecum. These findings of a distinct ileitis and proximally accentuated colitis are not specific. Architectural and regenerating epithelial changes and fibrosis indicate a sustained or previous damage of the mucosa. Screening for Clostridium difficile toxin using ELISA as well as cultures for Clostridium difficile and Salmonella, Shigella, and Campylobacter species remained negative. With supportive therapy, gastrointestinal symptoms as well as inflammatory markers showed a tendency to regression so that the patient could be dismissed in good shape on day 17 after ingestion of Amanita. Diarrhea and varying abdominal pain persisted over several weeks thereafter. Clinical follow-up after six months showed a completely symptom-free patient.


A 52-year-old female was admitted to the hospital to treat a huge liver tumor with complaints of dyspnea, severe abdominal distension, and lower-extremity edema. Hepatitis B virus surface antigen (HBs-Ag) and hepatitis C virus antibody (HCV-Ab) were negative. The serum level of DUPAN-II was 810 U/ml and that of CA125 was 157 IU/ml, and alpha-fetoprotein (AFP), protein induced by vitamin K absence (PIVKA-II), carcinoembryonic antigen (CEA), and carbohydrate antigen 19–9 (CA19-9) were in the normal range. Computed tomography (CT) showed a huge low-density tumor with a clear margin, 23 cm in diameter, and showed little enhancement after administration of contrast medium (Fig. ). Magnetic resonance (MR) imaging demonstrated the multicystic tumor to be hypointense on T1-weighted images (Fig. ) and hyperintense on T2-weighted images (Fig. ). A right tri-sectionectomy as the first operation was performed safely and successfully, even though the tumor entirely compressed the inferior vena cava and the root of three hepatic veins. Operation time was 13 h and intraoperative bleeding was 2400 g. Resected specimen showed a heterogenic tumor sized 23 × 22 × 11 cm (Fig. ). Histologically, spindled, oval, or stellate tumor cells were distributed in myxoid or fibrous stroma. Multiple varying-sized cytoplasmic eosinophilic globules were seen (Fig. , ). Immunohistologically, tumor cells were positive for vimentin (Fig. ), alpha 1-antitrypsin (Fig. ), and alpha 1-antichymotrypsin (Fig. ), and partially positive for alpha-smooth muscle actin (SMA) and CD68/kp-1. S-100, calponin, cytokeratin, factor VIII, CD34, and AFP were negative in tumor cells. The MIB-1 index was 20 % (Fig. ). Finally, the tumor was histologically diagnosed as a UESL, and the liver parenchyma was normal liver. Twelve and 19 months after the first operation, for the sequential recurrent diseases, a left caudate lobectomy and a partial hepatectomy of segment 3 were performed as the second and the third surgery, respectively. Twenty months after the first operation, twice transarterial chemoembolizations (TACEs) with CDDP 50 mg + lipiodol 2.5 ml, epirubicin 30 mg, and gelatin sponge were performed. Twenty-five months after the first operation, a radio-frequency ablation (RFA) was performed (pre, Fig. , ; post, Fig. , ). Thirty-five, 42, and 47 months after the first operation, two times of partial hepatic resections and a hepatectomy in combination with RFA (pre, Fig. ; post, Fig. ) were additionally performed. Because of bone metastases and tumor thrombosis in azygos vein, she unfortunately died 62 months after the initial hepatectomy.


A 53-year-old female was admitted to our hospital with a huge liver tumor with symptoms of epigastralgia and back pain. Her HBs-Ag and HCV-Ab were negative. Serum level of PIVKA-II was elevated to 10,369 mAU/ml, and AFP, CEA, and CA19-9 were in the normal range. CT showed a huge low-density tumor sized 18 × 14 cm that showed mild enhancement after administration of contrast medium (Fig. ). MR imaging demonstrated the heterogeneous tumor to be hypointense on T1-weighted images (Fig. ) and hyperintense on T2-weighted images (Fig. ). Some satellite lesions suspected as cavernous hemangiomas were identified in the bilateral lobe of the liver. The first extended left hepatectomy was performed. Operation time was 459 min and intraoperative bleeding was 877 g. Resected specimen revealed a tumor with multiple components, sized 22 × 19 × 14 cm (Fig. ). Histologically, spindled, oval, or stellate tumor cells were distributed in myxoid or fibrous stroma. Nuclear pleomorphism and hyperchromasia with frequent multinucleated or bizarre giant cells were apparent. Multiple varying-sized cytoplasmic eosinophilic globules were seen (Fig. , ). The tumor cells were positive for vimentin (Fig. ), alpha 1-antitrypsin (Fig. ), alpha 1-antichymotrypsin (Fig. ), and desmin, and partially positive for CD34 and alpha-SMA. The MIB-1 index was 30 % (Fig. ). Hepatocyte specific antigen (HSA) and cytokeratin were negative in the tumor. The tumor was histologically diagnosed as a UESL in the normal liver. Three months after the first operation, a TACE (CDDP 80 mg + lipiodol 4 ml, 5-FU 1000 mg, and gelatin sponge) was performed. Four and 14 months after the first operation, a partial hepatic resection of segments 6 and 7 and a partial hepatic resection of segment 8 in combination with RFA (pre, Fig. ; post, Fig. ) were also performed, respectively. She is now alive without any recurrent diseases for more than 65 months from the initial hepatic resection.


The patient is a 24-year-old woman at 35 weeks' gestational age that presented to the emergency department with right flank pain. An US demonstrated a 15 cm infiltrating and partially cystic right renal mass. She was induced and had an uneventful vaginal delivery. A CT scan was performed which confirmed an enhancing 15 cm right renal mass (). She underwent right adrenal-sparing radical nephrectomy with paracaval lymphadenectomy. Final pathology from this surgery was reported as pT3aN1MX renal cell carcinoma of unclassified type (). The histology was described as cells arranged in well-organized papillae with hobnail features, intraluminal blue secretions, villous-like architectural features, and a focus of bizarre nuclear atypia. FISH analysis was negative for trisomy 7-, trisomy 17-, and TFE3 translocation-associated renal cell carcinomas. Some tumor cells were noted to have very large eosinophilic nuclei with subtle perinuclear clearing. A suspicion for papillary type II histology was raised and the patient was referred for genetic testing. Indeed, a heterozygous 698G>A mutation was noted in the FH gene consistent with a diagnosis of HLRCC. Four months after her right nephrectomy, she underwent PET-CT imaging which demonstrated an FDG-avid left adrenal gland in addition to multiple septated left renal cysts (). Given the known aggressive nature of HLRCC-associated type 2 papillary renal cell carcinomas, radical left nephrectomy with adrenalectomy and retroperitoneal lymph node dissection was performed and the specimen was submitted for pathologic analysis.
A left radical nephrectomy specimen and retroperitoneal lymph nodes were submitted for pathologic examination. Tissue underwent typical gross examination and sectioning. Formalin-fixed and paraffin-embedded tumor specimens were submitted in cassettes for microscopic examination. Hematoxylin and eosin staining was performed using a standard protocol on 20 tissue sections. Immunohistochemical stains for CK20, CA9, P504S, RCC, EMA, CK7, CD10, and vimentin were also performed on paraffin-embedded, formalin-fixed 4 μm using standardized protocols with internal and external controls. Staining for aberrantly succinated proteins was accomplished using the 2SC antibody.
The gross description of the kidney delineates multiple thin-walled cysts filled with greenish, cloudy fluid in the upper and lower pole of the left kidney. No solid mass was identified. The tissue sections corroborate this with multiple simple cysts lines by a single cell layer with bland cytology. Some cyst-lining cells demonstrate variable amount of eosinophilic cytoplasm and enlarged nuclei with open chromatin and occasional prominent nucleoli. One section contains a single small papillary frond. In comparison with the right nephrectomy tumor specimen, subtle cytological similarity is noted, particularly in the cells lining the cystic spaces containing the papillary tumor (). However, the cystic foci from the left kidney do not fulfill criteria for malignancy. 2SC staining of the benign cysts demonstrates profound uptake in the cells lining the cystic spaces similar to the 2SC staining pattern noted in the cystic components of the malignant right-sided type 2 papillary renal cell carcinoma.


A 47-year-old woman was diagnosed as papillary thyroid carcinoma. Total thyroidectomy was performed in our hospital and I-131 ablation therapy was administered four weeks after surgery. The whole-body scanning was performed on the 7th day of ablation and scintigraphy images revealed a focus of increased uptake in the right upper quadrant. Lateral view images of the uptake site showed that the focus was located in the vicinity of the right liver lobe ().
The patient was referred to radiology department for correlative abdominal Computed Tomography (CT) and US, to rule out a possible liver metastasis. The CT detected a gallstone in the corresponding area, which was also verified by US (). Neither examination identified metastatic disease in the liver or in other abdominal organs.


A 55-year-old, female, hypertensive, smoker (35 pack year) patient presenting with
dysphonia, mild dysphagia and persistent dry cough for four months. Videolaryngoscopy
demonstrated paramedian left vocal cord paralysis ().
Computed tomography of cervical and thoracic regions confirmed the videolaryngoscopy
findings () and defined the diagnosis by
demonstrating the presence of a focal, saccular aneurysm on the inferior wall of the
aortic arch (, and ), responsible for
stretching the left recurrent laryngeal nerve and causing the described symptoms.


A 43-year-old male smoker was diagnosed with non-union of a femoral shaft fracture. The fracture was sustained in July 2008 and managed with intramedullary nail fixation. For the non-union he had an unsuccessful revision nailing and subsequent drilling with bone marrow injection. In February 2009 the nail was removed and plate fixation with formal bone autograft in May 2009 resulted in bony union. Implants were removed and a unilateral external fixator was applied in January 2011 to correct shortening of the femur. He developed a DVT in April 2011 while the fixator was still in situ. He subsequently developed some symptoms of a post-phlebitic limb.


A 44-year-old male smoker of high BMI with a diagnosis of recurrent adamantinoma underwent excision of the lateral tibial cortex tumour and medullary curettage in April 2010. Due to a recurrence in November 2010, a segmental diaphyseal excision and application of a TSF was performed for bone transport. In the last month of a 4-month course of frame treatment he experienced a PE with symptoms of mild shortness of breath which fully resolved. Of note, this man was resident overseas and throughout the course of his frame treatment made several flights of over 3 h between the UK and his home.
Other than surgical time (Fig. ), 47 individuals had one risk factor, six had two, and three patients had three. Risk factors are summarised in Table .
Of the procedures for which records were obtained, patients received post-operative prophylactic dose low molecular weight heparin (LMWH) for 71 procedures. Forty of those who received LMWH had identifiable risk factors on review of case notes. Of the 31 without an identified risk factor, we have postulated the potential reason for the use of chemical thromboprophylaxis which is summarised in Table . If the first dose of chemical prophylaxis was more than 36 h post-operatively, the use of LMWH was thought to be due to prolonged immobility. For those with insufficient data to calculate a BMI, it was surmised that this was the risk factor for which LMWH was used. One individual had polio and another who underwent simultaneous application of an ipsilateral femoral and tibial frame may have been considered to be risks of thromboembolism.
Twenty patients were found to have risk factors for thrombosis but were not treated with chemical thromboprophylaxis, summarised in Table . Of 12 adults with high BMI, only three had a BMI over 40; four whose only risk factor was age > 60 were aged between 62 and 66. These cases of patients with a BMI and age close to the threshold of a risk of thrombotic event may not have had their risk status noted on clinical assessment.
Subsequent to this study population, there have been two further cases of DVT/PE in patients treated with external fixators by the senior authors. These cases were not included in the above data, but their histories are included below (Cases 3 and 4) to help inform further discussion.


A 53-year-old man with knee osteoarthritis secondary to malunion of a proximal tibial fracture sustained at age 26 underwent application of a Taylor Spatial Frame for deformity correction in November 2012. The frame was removed in March 2013. Three weeks after frame removal, calf swelling prompted an investigation and a DVT was found. Following a course of anticoagulant treatment he has no residual symptoms.


A 30-year-old male smoker was treated with a unilateral fixator to lengthen a malunited femoral shaft fracture, which had been sustained with other injuries in a traffic collision in August 2011. He developed multiple pulmonary emboli and respiratory symptoms for 3 days following osteotomy and application of fixator in October 2012. His symptoms fully resolved. It was noted that he had reduced mobility due to his accompanying injuries.


A 16-year-old healthy female, with a body mass index of 56, presented herself at the outpatient clinic of our hospital with a swelling of the left distal forearm that had developed slowly without a foregoing trauma. Her medical history did not reveal MO, nor did any family members suffer from MO. She visited our clinic because several close relatives suffered from other malignant diseases. She did not have any complaints at the first presentation, but a slightly limited rotation (pronation/supination of 60°/0°/45°). The overall Disabilities of the Arm, Shoulder and Hand (DASH) score was 7.5 []. There was no instability at the DRUJ or wrist. A bony swelling could be palpated at the dorso-ulnar side of the radius just proximal to the DRUJ. Radiography showed an exostosis at the ulnar side of the distal radius with reactive ulnar deformity. The ulna was thin and dysplastic due to usuration of the osteochondroma. The ulna curved around the exostosis with an ulna-14 mm configuration as a result (contralateral ulna-3 mm) (Fig. ). Because of the benign appearance, minimal complaints and acceptable range of motion, it was decided not to perform invasive treatment at that time, but to check the lesion again in 6 months time. After 6 months, she suffered from progressive pain and her range of motion had decreased. No change in radiological appearance was found. For further evaluation, an MRI was made, which showed the exostosis with an overlaying cartilage cap without malignant characteristics. In addition, the MRI showed a relatively normal concave shape of the sigmoid notch of the radius, indicating that the joint had originally developed normal.
The case was presented to the Dutch Orthopedic Bone Tumor Society, which concluded that the most likely diagnosis would be osteocartilaginous exostosis. The commission advised surgical resection and, if possible, reconstruction of the distal radioulnar joint.
The first surgical procedure consisted of resection of the exostosis; a combined dorsal and volar approach was needed, because of the size of the exostosis. Then, osteotomy of the ulna was performed and the articulating surface of the ulna redirected towards the radial notch. An external fixator with distraction device was placed over the ulna in such a way that the displaced ulna would eventually grow into the sigmoid notch (Fig. ).
Histology showed an osteochondroma, without malignant characteristics. Due to pain and swelling direct post-operatively, distraction of the ulna was not begun before 2.5 weeks after the first surgical procedure. Distraction was started with a rate of 0.5 mm per day for 2 weeks, but was reduced to 0.25 mm because of pain for the remaining period (when possible). During the distraction, the proximal ulna fragment deviated ulnarly resulting in a longer distraction time to reach the radial notch. In the distraction period, the patient developed a superficial infection at the external fixator pins. This infection was treated with oral antibiotics.
Three months after the first procedure, the ulna had covered 12 mm gap in length and the DRUJ appeared congruent; however, the distraction gap was not entirely filled with bone, indicating delayed union. Furthermore, the distracted ulna showed an angular deformity in the distracted area. Therefore, 3 months after the first procedure, the traction device was replaced by a static external fixator after reduction in the ulna. Post-operative treatment consisted of the use of a bone growth stimulator for 4 months. Only minimal signs of callus formation were seen after 4.5 months, and the patient experienced limitations in range of motion at her work as kindergarten teacher because of the external fixator. Therefore, the external fixator was removed, and plate osteosynthesis combined with bone grafting was performed. The defect was filled with autologous bone harvested from the crista iliaca bone combined with a demineralised bone graft system. (BONUS II DBM Matrix from Biomet Biologics Inc, Warsaw, IN, USA.)
Clinical and radiological consolidation was achieved at 27 months after the first procedure. At final follow-up, 51 months after the first procedure, patient was very satisfied and the positive result of this procedure had encouraged her to have bariatric surgery. Her BMI had dropped from 56 to 30 resulting in slightly irritation of the plate. The VAS for pain score was 0. Clinical investigation revealed an excellent range of motion with flexion/extension 80°/0°/80° and pronation/supination 80°/0°/85°. The DRUJ was stable, and the grip strength of the wrist was equal to the controlateral wrist (right: 28 kg and left: 26 kg). Radiographs showed a normal sized ulna and a congruent DRUJ (Fig. ). The overall DASH score was 7.5 and when corrected for her job 6.6. She had resumed her studies and resumed her work as kindergarten teacher and clothes store co-worker. Because of the slight irritation, it was decided to remove the plate in the near future.


A Chinese girl, aged 7 years and 3 months, was diagnosed with AS on February 11, 2006. This was the first case of AS to be diagnosed on the mainland of China, to the best of our knowledge (). Two years and 9 months prior to diagnosis, the patient had been admitted to a local hospital due to generalized hyperpigmentation and emaciation, in addition to a 3-min period of unconsciousness. The laboratory examination revealed that the blood electrolyte and serum cortisol levels of the patient, as well as the liver and kidney function, were normal; however, the levels of adrenocorticotropin (ACTH) were markedly elevated. A computed tomography scan of both adrenal glands and a magnetic resonance imaging (MRI) scan of the head revealed no significant anomalies. The patient was diagnosed with Addison's disease, and the hyperpigmentation slowly dissipated with oral hydrocortisone acetate (50 mg/m2).
Nine months prior to admission to the Beijing Children's Hospital, the patient had a vomiting incident without abdominal pain or regurgitation, which lasted 5–6 days. Treatment with an increased dose of hydrocortisone was not effective, and the patient exhibited increasing levels of weakness, fatigue, difficulty in eating and weight loss.
The parents of the patient were healthy (father, 30 years old; mother, 32 years old). Gravida 1 (G1) and (G2) were aborted; the patient was G3 para 1 (P1) with full-term, normal delivery, and her intelligence was determined to be normal, as compared with children of the same age. Consanguineous relationships between the parents were found to exist for at least the previous three generations ().
The findings of the physical examination were as follows: Blood pressure (BP), 90/60 mmHg; height, 120 cm; weight, 15 kg. No abnormalities were observed in the heart or lungs of the patient. The breast development stage of the patient was determined to be Tanner stage I (). The mental status of the patient was evaluated as alert but weak. Hyperpigmentation of the skin and thin subcutaneous fat were noted (). Normal muscle strength and tone were found in all extremities, but muscle volume was reduced and a flattening of the thenar eminence was observed. The abdominal reflex was positive, while the knee jerk, Achilles tendon and radial periosteal reflexes were found to be hyperreflexive. The patient was negative for meningism and positive for the Babinski sign on the right side. No abnormal gait was observed. The electroencephalograms (EEGs), brain MRI scan and evoked potential and nerve conduction studies showed no specific abnormalities. Esophagography showed achalasia of the lower esophagus at the cardia (). Funduscopy indicated that the optic nerve discs were pale, suggesting optic nerve atrophy. The results of a bilateral Schirmer test were 0 mm, which led to a diagnosis of alacrima. Further medical history revealed that, not long after birth, the patient was unable to produce tears when crying. The suspicion that the patient was positive for AS was confirmed by genetic testing, which revealed a c.771delG mutation in exon 8 of the AAAS gene (). The parents refused follow-up care for this patient, due to ‘familial reasons’.


A male patient, aged 2 years and 7 months, was admitted to the hospital on March 2, 2013 with a 1-year history of vomiting after either overeating or rapid eating. No apparent causes or obvious weight loss had been observed.
Six months prior to admission, the parents noted hyperpigmentation in the lips, photophobia and frequent blinking following birth. The patient was treated for dry-eye syndrome due to alacrima. There was no documented family history of adrenal gland disease. The parents did not have a consanguineous relationship and were in good health. The patient was G1P1 and the birth weight was recorded at 3.45 kg; the intellectual and physical development of the child was determined to be normal, as compared with children of the same age.
The findings of the physical examination were as follows: BP, 86/50 mmHg; height, 92 cm; weight, 13 kg. The heart, lungs, abdomen, nervous system and external genitalia of the patient were found to be normal. Hyperpigmentation was observed over most of the body. Esophagography showed achalasia of the lower esophagus at the cardia. The patient was unable to produce tears when crying but refused to undergo the Schirmer test; therefore, an MRI scan () was performed in order to confirm lacrimal gland hypoplasia and diagnose alacrima. The clinical diagnosis was AS. Genetic testing confirmed the presence of a c.771delG mutation in exon 8 of the AAAS gene. (). On day 3 after admission, the patient had a hypoglycemic episode and convulsion occurred due to an adrenal crisis. In response, the patient was treated with 100 mg/m2 hydrocortisone; the ACTH level decreased from >1,250 to 6.8 pg/ml (normal range, 0–46 pg/ml), and the hydrocortisone dosage was reduced to 20 mg/m2. Although the vomiting continued, without relationship with overeating, the patient was able to eat every day. The growth and nutritional status of the patient was found to be normal after 18 months of follow-up care.


A female patient, aged 4 years and 4 months, was admitted to the hospital with a 3-year history of vomiting small amounts following every meal. No obvious causes of the vomiting were identified. Approximately 2 years prior to admission, the patient exhibited hyperpigmentation of the lips, in addition to fatigue, with a slow/stagnating increase in weight and height.
One month prior to admission, the patient had a seizure and was diagnosed with secondary epilepsy, based on an abnormal EEG. The patient was successfully treated with Topamax but continued to vomit >10 times/day. The patient was G2P2 with full-term normal delivery and a birth weight of 3.35 kg. The intellectual and physical development of the patient was similar to that of healthy children of the same age. There was no family history of genetic diseases, and the parents were in a non-consanguineous marriage.
The findings of the physical examination were as follows: BP, 85/55 mmHg; height, 92.7 cm; weight, 12 kg. The patient was mentally alert, and no significant anomalies were observed in the heart, lungs, abdomen, nervous system or external genitalia. A generalized hyperpigmentation was observed. Esophagography showed achalasia of the lower esophagus at the cardia. In the hospital, the patient was observed not to produce tears when crying. The results of a bilateral Schirmer test were 0 mm, which led to the diagnosis of alacrima. Further medical history confirmed that the alacrima had manifested at birth. Following the diagnosis of AS, the patient was treated with hydrocortisone replacement therapy (25 mg/m2), and the vomiting was alleviated. Genetic testing confirmed a c.1366C>T mutation in exon 15 of the AAAS gene (). No additional follow-up information is available for this patient.


A 43-year-old female presented with swelling in the right inguinal region. The right inguinal bulge protruded with coughing and gradually became more conspicuous over the last 4 years. The painless bulge had persisted for 2 years prior to her presentation. On physical examination, a soft mass measuring approximately 4.0 cm in diameter was palpable in the right inguinal region. Patient’s vital signs and laboratory data were normal, with no history of local trauma noted.
MR imaging of the pelvis was performed with a 1.5-T magnetic resonance imaging (MRI) system (Gyroscan ACS NT; Philips Medical Systems, Germany). MR hydrography was performed using a SENSE body coil. A three-dimensional (3D) fast spin-echo imaging was applied as part of the comprehensive MR imaging examination was typically performed in patients. Parameters for 3D fast spin-echo imaging were as follows: repetition time/effective echo time, 3000 msec/721.7 msec; echo train length, 114; flip angle, 90°; section thickness, 2 mm; no gap between sections; field of view, 230 mm; matrix, 256 × 512; and acquisition time, 3 min 39 s. The MRI revealed an irregularly shaped cystic mass lesion measuring 48 × 37 mm in the right inguinal region, with a smaller cystic lesion and fluid collection evident in the right side of the pelvic cavity. These cystic lesions were isointense with muscles in the T1-weighted images and had marked high intensity on T2-weighted images. The T2-weighted images showed the cystic mass extending both within and outside the inguinal canal along the course of the right round ligament (Fig. ). Neither intestinal nor omental components were identified in the cystic mass. Axial T2-weighted images showed multiple masses of low intensity in the uterus that were consistent with uterine myomas. Maximum intensity projection (MIP) imaging of MR hydrography showed that the right inguinal cystic mass lesion and the intrapelvic cystic lesion together formed an uninterrupted cystic lesion measuring 13.5 cm in diameter, with constrictions at the internal and external inguinal rings (Fig. ). These findings seemed to indicate that the lesion was either a hydrocele of the canal of Nuck or endometriosis due to the minimal internal hemorrhagic component.
Surgery revealed that the cystic mass included a serous component extending from the right inguinal canal to the pubis adherent to the round ligament of the uterus (Fig. ). High ligation at the internal inguinal ring and resection of the outside of the cystic lesion was performed; however, the adhered cystic lesion could not be dissected off from the round ligament, and a mesh plug repair was subsequently performed. The cystic lesion in the intrapelvic cavity remained after surgery. Pathological examination showed that the cystic lesion of irregular and fibrotic thick wall with a large number of small vessels had marked hemorrhages, histiocytic infiltration with phagocytosed hemosiderin, and inflammatory granulation tissue. Although a reddish mass lesion was found on the intracystic wall on gross pathologic examination, there was no evidence indicative of malignancy or endometriosis. These findings indicated that further surgery was not required for the remaining lesion, and a final diagnosis of hydrocele of the canal of Nuck was made. Postoperative recovery was uneventful, and the patient was eventually discharged. No recurrence of a mass in the inguinal region has occurred.
During embryonic development, the round ligament is derived from the gubernaculum, which is attached to the uterus near the origin of the fallopian tube. The cranial part of the gubernaculum becomes the ovarian ligament, whereas the caudal part forms the round ligament of the uterus. The round ligament runs through the internal ring, inguinal canal, and external ring, attaching terminally to the abdominal wall muscles []. The processus vaginalis accompanies the round ligament through the inguinal canal into the labium majus []. This evagination of the parietal peritoneum is the canal of Nuck in the female and corresponds to the processus vaginalis peritonei in the male. In males, this structure accompanies the spermatic cord into the inguinal canal before it reaches the scrotum. Normally, this peritoneal evagination undergoes complete obliteration during the first year of life []. When the processus vaginalis fails to close, the patient may develop a hernia or hydrocele. A hydrocele of the canal of Nuck, which is a collection of fluid within the processus vaginalis in females, is a rare entity, and it is analogous to a spermatic cord hydrocele [–].
Clinically, a hydrocele of the canal of Nuck can appear either as a painless or a moderately painful fluctuant inguinal mass, with no accompanying nausea or vomiting; therefore, it is not easy to diagnose this entity on clinical findings alone. These masses are not reducible and, if large enough, can be transilluminated. When the peritoneal evagination remains completely patent, it forms an avenue for an indirect inguinal hernia. Partial proximal obliteration, which leaves the distal portion of the processus vaginalis open, creates the anatomic prerequisite for a hydrocele of the canal of Nuck [–]. In adults, a hydrocele of the canal of Nuck should be first treated by surgical excision of the mass without puncturing it. Aspiration of a hydrocele of the canal of Nuck is inadequate and results in high recurrence rates. When the hydrocele is complicated by endometriosis, excision of both the mass and uterine round ligament is necessary [, , ].
The MRI findings for the canal of Nuck hydroceles have been reported for a few patients. In those reported by Park et al. [] and Safak et al. [], the hydrocele appeared as a thin-walled, tense cystic mass in the inguinal area. A hydrocele of the canal of Nuck has low intensity in T1-weighted images and high intensity in T2-weighted images. MRI reveals that these hydroceles extend both within and outside the inguinal canal and demonstrates the extension of the hydroceles very well, which allows for successful surgical excision. In the present case, the MRI revealed a cystic lesion, which extended along the round ligament from the pelvic cavity to the inguinal region. In addition, it enabled visualization of other internal structures which were neither omentum nor intestine in the cystic lesion; thus, this led us to a preoperative suspicion of a hydrocele of the canal of Nuck. Furthermore, the cystic lesion showed a slight increase in intensity compared with that of the muscles in the T1-weighted images. It is possible that this represented cystic lesions with minimal hemorrhagic changes. Although the cystic lesion was suspicious for a hydrocele of the canal of Nuck with endometriosis (so-called Nuck canal endometriosis), the histological examination revealed no evidence of endometriosis.
There are many causes of swelling in the female inguinal region, including inguinal hernia, tumors (lipoma, leiomyoma, and sarcoma), cysts, abscesses, and lymphadenopathy. When a hydrocele occurs in the vulva, the differential diagnosis should include a Bartholin gland cyst and a Gartner duct cyst. The hydrocele of the canal of Nuck is now believed to be more common than in previous reports; however, it is still an unfamiliar problem for physicians, and some cases are preoperatively misdiagnosed as inguinal hernias, Bartholin cysts, or Bartholin abscesses [, , , ]. It is important for clinicians, including surgeons and radiologists, to know and understand this entity accurately because many differential diagnoses are listed for inguinal masses in females. Ultrasonography is often used for the initial imaging of inguinal lesions. In previous reports, ultrasonographic findings of a hydrocele of the canal of Nuck have been described as a comma-shaped lesion with its tail directed toward the inguinal canal, a “cyst within a cyst” appearance, and a multicystic hydrocele. However, ultrasonography seems to be controlled by the capability of the specialist, and this examination lacks reproducibility. Moreover, there is a limited view and it is difficult to image the entirety of a large mass, as in this case, and to understand its relativity with surrounding tissues. Because MRI captures the same image, it is possible to share and understand the information. In addition, MR hydrography allows an easy grasp of the form of hydrocele from the liquid component, which is visualized as a high signal. Furthermore, it is necessary to understand the extension of the cystic lesion for proper surgical planning. MRI can be used effectively both as an imaging technique as well as a way to evaluate the extent of this condition. In particular, MR hydrography can identify the cystic mass form and can evaluate the excision range better and with more ease than other imaging modalities.


In March 2007, a 21-year-old female underwent a right salpingo-oophorectomy, partial omentectomy and appendectomy due to right ovarian cancer at the Department of Obstetrics and Gynecology, Ehime University Hospital (Toon, Japan). Pathological examination of the tumor revealed multiple mucinous cysts, lined by mucinous tumor cells. Although adenomatous and borderline malignant regions were identified in the tumor, partial areas of carcinoma were also present, which proliferated and invaded the stroma. Thus, the ovarian tumor was diagnosed as mucinous cystadenocarcinoma. After performing adjuvant chemotherapy with three 28-day cycles of carboplatin (2 AUC; days 1, 8 and 15) and paclitaxel (60 mg/m2; days 1, 8 and 15), follow-up care was conducted on an outpatient basis every 3 months.
At 2 years and 6 months post-surgery, follow-up contrast-enhanced computed tomography (CT) showed two low density areas in the spleen. Thus, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT was performed and revealed two abnormal high uptake lesions in the spleen, which were 2.5 and 1.0 cm in diameter, with a maximum standardized uptake value (SUVmax) of 21.0 and 18.2, respectively. The PET/CT also showed an abnormal high uptake lesion in the lateral segment of the liver, which was 1.5 cm in diameter, with an SUVmax of 14.5 ().
In October 2009, the patient was referred to the Department of Hepatobiliary-Pancreatic and Breast Surgery of Ehime University Hospital due to a working diagnosis of splenic and hepatic metastases from right ovarian cancer. A splenectomy and partial hepatectomy were recommended and the patient was admitted. Contrast-enhanced CT was performed again prior to admission and showed a low-attenuation nodule in the lateral segment of the liver, in addition to two low-attenuation nodules in the spleen (). Hepatomegaly and splenomegaly were not indicated on the radiology report. Abnormal lesions in the lung and bilateral hilar lymphadenopathy were also not indicated. At the time of admission, the patient was 162.3 cm tall and weighed 93.3 kg. The body mass index was 35.4 and the patient exhibited no swelling of the superficial lymph nodes. Routine blood analysis showed that the complete blood count, and test results for liver function, renal function and electrolytes, including serum calcium, were within normal limits, with the exception of a slightly elevated level of C-reactive protein (1.20 mg/dl; normal range, 0.00–0.20 mg/dl) (). The serum levels of carcinoembryonic antigen, cancer antigen (CA)19-9, CA125 and α-fetoprotein were normal on admission, although the serum levels of CA19-9 (45 U/ml; normal range, <37 U/ml) and CA125 (56.8 U/ml; normal range, <35 U/ml) had been elevated prior to the previous surgery for right ovarian cancer. Electrocardiogram and chest X-ray results were normal ().
Due to the fact that the main differential diagnosis was splenic and hepatic metastases from right ovarian cancer, a laparoscopic procedure was performed. At the beginning of the laparoscopic procedure, an exploration of the abdominal cavity by a gynecologist was performed, which confirmed no abnormalities in the uterus or the adnexa of uterus, and no ascites or peritoneal dissemination. A cytological sample of peritoneal washing in the pouch of Douglas was obtained, and the presence of no malignant cells in the sample was confirmed the following day. The laparoscopic splenectomy and partial hepatectomy were then performed. Tumors were observed on the surface of the spleen (). Although a tumor was not observed on the liver, a 1.5-cm low echoic mass in segment 3 (Couinaud classification) () of the liver was confirmed by intraoperative ultrasonography. The whole spleen was removed after a 12-mm median incision for a port was widened by 4 cm. The weight of the spleen was 269 g. The weight of the resected liver specimen was 34 g. Macroscopically, yellow-whitish and elastic-hard nodules were found in the specimens on the sectional views (). Histopathological examination showed that these nodules contained no malignant cells and that a large number of non-caseating epithelioid cell granulomas formed these nodules (). Acid-fast bacillus was not detected using Ziel-Nielsen staining. Fungus was also not detected using periodic acid-Schiff staining and Grocott staining. Thus, the final diagnosis was of extrapulmonary sarcoidosis of the liver and spleen. Further post-operative laboratory studies showed no angiotensin-converting enzyme (ACE; 11.4 IU//l; normal range, 8.3–21.4 IU/l) or lysozyme (6.5 µg/ml; normal range, 5.0–10.2 µg/ml) abnormalities.
The patient recovered well with no further treatment, such as steroid therapy, and neither recurrence of sarcoidosis in any other organs nor recurrence and metastasis of right ovarian cancer have been observed for 2 years and 5 months since the surgery. At 5 years and 6 months post-surgery the patient remained alive.


A 74-year-old female came to our emergency department (ED) with fever and dysuria of 3 days duration. She was in Peru a week prior to presentation and had similar complaints. She was seen by a local physician there and was told that she had a urinary tract infection. She received a one-time injection of an unknown medication after which she felt much improved. She then travelled to the United States and had been here for 3 days after which her symptoms recurred.
Her medical history was notable for hypertension. She had no prior illness that required hospitalization and led a relatively healthy lifestyle. She had an unremarkable family history including no history of sudden death.
In the ED, she was noted to have a temporal temperature of 39°C, tachycardia at 101 bpm with a blood pressure of 129/49 mm Hg; her physical exam was unremarkable. Laboratory data were notable for leukocytosis with bandemia and pyuria. She was to be admitted for sepsis from a urinary tract infection. Within an hour she complained of increasing chills, and a repeat rectal temperature was 41°C. Prior to administration of antipyretics she developed a generalized tonic–clonic seizure. A computed tomography scan of the head was unremarkable. She was not on a cardiac telemetry at the time of the seizure.
An ECG was obtained that showed sinus tachycardia at 106 bpm with coved ST segment elevation in leads V1 and V2 (more pronounced in V2), characteristic of the Brugada ECG pattern (). Echocardiogram showed normal left ventricular systolic function with a left ventricular ejection fraction of 55% to 60% and no segmental wall motion abnormalities or valvular abnormalities. Her blood work was notable for mild elevation of troponin I at 1.5 ng/mL (normal reference range = 0.0-0.5 ng/mL), which was attributed to demand ischemia. Repeat ECGs during the febrile period continued to show the same precordial ST segment changes. Telemetry revealed no significant events. She had no further seizures. A neurologist was consulted who recommended no further workup for her first and one-time seizure episode.
After 48 hours of intravenous antibiotics, she showed clinical improvement and was no longer febrile. A repeat ECG with normal temperature demonstrated reversibility of her classic Brugada type 1 changes with clinical defervescence (). She had no history of prior syncope, seizure, or palpitations. She refused to undergo any interventional studies; therefore, a cardiac catheterization and an electrophysiological study were not performed despite our recommendation.
At the time of discharge she was advised to have prompt intervention with antipyretics for any future febrile episodes and also to avoid certain medications (see Discussion). At 2-month follow-up, she remains well and free of cardiac events.


Patient 3 is a 6-year-old girl born as the first child of a French mother and an unknown father. Her 3-year-old maternal half-brother shows normal development. The mother, who was 15 years old at the birth of her daughter, has mild intellectual disability and poor language abilities. She has normal measurements without micro- or brachycephaly and no seizure history. Her only dysmorphisms are mildly anteverted nares and a dimpled chin.
Patient 3 was born at gestational week 35 with a weight of 2630 g (50th centile), a length of 45 cm (25th centile, −1.0 S.D.), and an OFC of 31 cm (10th centile, −1.5 S.D.). Mild muscular hypotonia was noted as well as talus valgus. She started walking at the age of 14 months and walked without support at 22 months. Neither feeding difficulties nor obesity were reported in the first 2 years of life. There was no active speech development. Her recurrent otitis was treated repeatedly with transtympanic drains.
Upon clinical genetic examination at the age of 4 years and 5 months, her weight was 13 kg (3rd centile, −2.0 S.D.), her height was 92 cm (3rd centile, −2.0 S.D.), and her OFC was 45.5 cm (3rd centile, −2.0 S.D.). She was microcephalic but not brachycephalic. A high frontal hairline, convergent strabismus, a short nose with anteverted nares and a dimpled chin were noted (Fig. ). Hands and fingers were normal. Language development was severely delayed with only few syllables and cries as vocalizations. She showed stereotypic hand movements and autistiform behavior. She suffered from seizures which were treated with Valproate. A cerebral MRI scan showed bilateral temporal-occipital pachygyria with heterogeneous “nodules” of grey cortex. Upon examination at the age of 6 years, her weight was 19.4 kg (25th centile, −0.5 S.D.), her height was 105 cm (3rd centile, −2.0 S.D.), and her OFC remained at 48 cm (3rd centile, −2.0 S.D.). Severe intellectual disability, muscular hypotonia, and autistic behavior were still present. She showed bruxism and her language was limited to repeating single words. She had strabismus, a short nose with anteverted nares, and a flat face, as well as long and thin fingers and pes planus. At the age of 9 years, she was still reported to have no active speech and to have remained seizure-free under treatment for 20 months.
FMR1 analyses by PCR and Southern blot and MECP2 analysis (DHPLC) gave normal results.


Patient 4 is a 5 year and 6 months old girl born prematurely after 27 weeks of gestation because of a placental hematoma. Her unrelated parents are of French descent and there is no particular familial history of genetic disease. Birth weight was 950 g (65th centile, +0.5 S.D., age-corrected), height was 34 cm (37th centile, −0.5 S.D.), and OFC 24 cm (29th centile, −0.5 S.D.). Bilateral talipes equinus and a patent ductus arteriosus which required surgical treatment were noted at birth. She had retinopathy of prematurity with vitreous hemorrhage as well as bilateral microphtalmia and alternate strabismus. At the age of 2 months, she presented with generalized seizures with persistent, almost daily crises which were resistant to treatment. A brain MRI gave normal results. Arm and forearm X-rays showed diffuse bone demineralization and radiocubital synostosis.
She was first referred for clinical genetic evaluation at the age of 5 months. Dysmorphic features including high frontal hairline, telecanthus, upslanting palpebral fissures, arched eyebrows, flat nasal bridge, thin upper lip, and retrognathism were noted (Fig. ). She also had bilateral 5th finger clinodactyly, absent thumb nails, and arched and abnormal nails of both index fingers. Her weight was 3625 g (5th centile, −1.9 S.D., age-corrected), height 49.5 cm (1st centile, −2.5 S.D., age-corrected), and OFC 35 cm (<3rd centile, −3.2 S.D.). Standard karyotyping gave normal results. At last examination at the age of 5 years and 6 months (Fig. ), she still had developed no active language but showed eye contact and was able to smile. Sitting without support had not been acquired. Her weight was 16 kg (8th centile, −1.8 S.D.), height 96 cm (below the 1st centile, −3.5 S.D.), and her OFC 47 cm (2nd centile, −2.2 S.D.). Nephropathy was diagnosed and CT scans at the age of 5 years and 6 months showed non-ossified and dislocated patellae, with bilateral patellar tendon hypoplasia.


A 27-year-old female admitted to the emergency unit with severe dyspnea at the postoperative third day of the cesarean section. She expressed that she had no respiratory symptoms until the seventh month of her pregnancy; subsequently she developed exertional dyspnea. Because of intrauterine growth retardation, she gave birth in the 35th week of the pregnancy by Cesarean section. Physical examination on admission revealed tachypnea, tachycardia, and loud second heart sound. In room air, she had hypoxemia (PaO2: 51 mmHg) and hypocarbia (PaCO2: 28 mmHg) with oxygen saturation (SaO2) of 85%. D-dimer was 2281 μg/L. Transthoracic echocardiography showed dilated right atrium and ventricle, tricuspid regurgitation, and normal left ventricular function with ejection fraction of 62%. Pulmonary artery pressure was 142 mmHg. Thorax computed tomography (CT) scan showed bilateral dilated pulmonary arteries and no sign of pulmonary thromboembolism. Oxygen and low molecular weight heparin were promptly started. On the third day of the treatment, SaO2 was 93% in room air. Hemoglobin was 16.2 g/dL, and hematocrit was 50.5%. Chest X-ray showed normal cardiothoracic index and bilateral dilated pulmonary arteries. ECG was in normal sinus rhythm with right axis deviation, incomplete right bundle branch block, and negative T waves between V1 and V4. Lower extremity Doppler ultrasonography (USG) was normal. No evidence of rheumatologic diseases could be found in her medical history. Rheumatologic markers were negative except speckled positive antinuclear antibody (ANA) with a titer of 1/160. Pulmonary perfusion scintigraphy was not diagnostic for pulmonary thromboembolism but showed systemic extrapulmonary accumulation of Tc99m-MAA in kidneys, spleen, and cranium which indicates right to left shunt (). Transesophageal echocardiography was performed but did not reveal any additional findings to the transthoracic echocardiography. Right heart catheterization and aortic root injection showed a large APW and Eisenmenger syndrome with severe pulmonary hypertension with a pulmonary artery pressure of 131/32/97 mmHg and increased pulmonary vascular resistance of 9 Wood units/m2 (Figures , , and ). Vasoreactivity test with adenosine was negative. Because of the presence of Eisenmenger syndrome, closure of the APW was contraindicated. Endothelin receptor antagonist and warfarin were started. At follow-up, she was asymptomatic and SaO2 was 95% at rest; however she had dyspnea and became desaturated at exertion.