Kiyoshi Gomi

Perivascular epithelioid cell tumor with SFPQ/PSF-TFE3 gene fusion in a patient with advanced neuroblastoma.

We report a case of perivascular epithelioid cell tumor (PEComa) with an SFPQ/PSF-TFE3 gene fusion in a 14-year-old girl treated for adrenal neuroblastoma for 4 years. Imaging studies revealed a tumor in the wall of the sigmoid colon, which was radiologically different from the neuroblastoma, together with several inguinal and cervical lymph node metastases of the neuroblastoma. Microscopically, the tumor in the sigmoid colon showed sheet-like growth of epithelioid cells with abundant clear cytoplasm and round nuclei, which were separated by thin fibrovascular septa. These epithelioid cells were immunohistochemically positive for vimentin, gp100 (detected with monoclonal antibody HMB-45), and TFE3, and the tumor was diagnosed as PEComa. In a fluorescence in situ hybridization assay using an in-house probe for TFE3, the tumor cells showed split signals, indicating a rearrangement of TFE3. Molecular cloning using 5′ rapid amplification of complementary DNA ends and subsequent reverse transcription-polymerase chain reaction revealed an SFPQ/PSF-TFE3 gene fusion. To the best of our knowledge, this is the second reported case of metachronous PEComa subsequent to a primary tumor, and the first report confirming an SFPQ/PSF-TFE3 gene fusion in PEComa.

Epithelioid angiomyolipoma of the kidney

Epithelioid angiomyolipoma (eAMLoma) is an uncommon renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis (TSC). It is composed of polygonal large‐sized tumor cells arranged in an epithelioid manner. Differential diagnosis from renal cell carcinoma (RCC) is often challenging because of its epithelioid morphology. Herein is reported three cases of eAMLoma, involving one in a 28‐year‐old man with TSC and two in women without TSC (34 and 62 years of age, respectively). The male TSC patient had microscopic conventional AMLomas in the same kidney. All patients were positive for melanoma (reactive with HMB45 antibody, and positive for melan A, tyrosinase and microphthalmia transcription factor) and smooth muscle markers (positive for α‐smooth muscle‐specific actin), but not for epithelial markers (cytokeratin, epithelial membrane antigen). In particular, the translocation RCC is an important differential diagnostic candidate, in terms of the positive reaction with HMB45 and morphological similarity. The present tumor samples did not show any reactivity for transcription factor binding to IGHM enhancer 3 or transcription factor EB, which excluded the possibility of translocation RCC. The possibility of eAMLoma should be evaluated as a diagnostic candidate, especially in cases of renal tumors (i) in young patients; (ii) associated with TSC; or (iii) with an epithelioid morphology and a high nuclear grade.

NUT midline carcinoma: report of 2 cases suggestive of pulmonary origin.

In this study, we report 2 pediatric cases of nuclear protein of the testis (NUT) midline carcinoma (NMC) suggestive of pulmonary origin: case 1 was a 14-year-old Japanese boy and case 2 was a 7-year-old Japanese girl. Initial symptoms of both cases were prolonged cough and chest pain, and the case 2 patient also complained of lumbago and lumbar mass due to bone metastases. Imaging studies revealed that pulmonary tumors from both patients were located at the hilar region of the lower lobe. Biopsies of the tumors showed undifferentiated carcinoma in case 1 and combined undifferentiated and squamous cell carcinoma in case 2. Despite intensive treatment with chemotherapy and radiation, progression of neither tumor was controlled, and both patients died of the tumors at 1 year (case 1) and 4 months (case 2) after onset of disease. Both tumors were diffusely positive for p63 and NUT expression and were partially positive for various cytokeratins. Reverse transcription polymerase chain reaction analysis and subsequent direct sequencing revealed that the bromodomain-containing protein 4-NUT chimeric gene was present in tumor tissue of both patients, leading to a diagnosis of NMC. The tumor cells of case 1 were also positive for thyroid transcription factor-1 expression, but those of case 2 were negative. Histologic examination of the surgically removed lung tumor of case 1 indicated that the origin of the tumor was basal cells of the bronchiolar epithelia.

Urinary Cytologic Features of Primary Large Cell Neuroendocrine Carcinoma of the Urinary Bladder

BACKGROUND Little is known about urine cytology of large cell neuroendocrine carcinoma (LCNEC) of the bladder. We report a case of primary LCNEC of the bladder, focusing on urinary cytology. CASE A 76-year-old woman who had a history of transurethral resection for urothelial carcinoma of the bladder visited our hospital because of intermittent gross hematuria. Urinary cytology on this visit identified atypical cells, interpreted initially as urothelial carcinoma. Cystoscopy detected a tumor apart from the previous bladder urothelial carcinoma. The diagnosis of LCNEC was pathologically confirmed after the transurethral resection; subsequently radical cystectomy and bilateral pelvic lymphadenectomy were performed. Based on the review of urine cytology for this tumor, neoplastic cells possessed rosette and nuclear molding arrangements with finely or coarsely granular, hyperchromatic nuclei. The average nuclear size of the neoplastic cells was 10.3 microm, whereas the average cell size was 14.9 microm. These cells were immunocytochemically positive for synaptophysin, consistent with LCNEC. The operative course for this patient was uneventful, and LCNEC had not recurred in the 48 months since cystectomy. CONCLUSION Our observations suggest that urinary cytology in combination with morphometry and immunocytochemistry may be a potentially useful method for the detection of LCNEC of the bladder.

Papillary carcinoma with extensive squamous metaplasia arising from thyroglossal duct cyst in an 11-year-old girl: significance of differentiation from squamous cell carcinoma: a case report.

We report a case of papillary carcinoma (PC) with extensive squamous metaplasia arising from a thyroglossal duct cyst (TDC) that required differential diagnosis from squamous cell carcinoma (SCC). An 11-year-old Japanese girl presented with a 9-month history of an anterior-midline neck mass that was clinically diagnosed as TDC. Open neck biopsy revealed nested proliferation of atypical squamous cells within the cystic structures, and SCC arising from TDC was initially suspected. Further examination, however, including immunohistochemistry, revealed the tumor to be of thyroid cell origin. The patient underwent wide local resection of the thyroglossal duct carcinoma by Sistrunk procedure and cervical lymph node dissection. Microscopically, the diagnosis was of PC with extensive squamous metaplasia and metastasis to the medial submandibular lymph node. Distinction of squamous metaplasia in PC from SCC is sometimes difficult, but has a significant effect on postoperative management.

Sacrococcygeal yolk sac tumor developing after teratoma: a clinicopathological study of pediatric sacrococcygeal germ cell tumors and a proposal of the pathogenesis of sacrococcygeal yolk sac tumors.

PURPOSE We evaluated the clinicopathological characteristics of pediatric sacrococcygeal germ cell tumors (SGCTs) and yolk sac tumors (YSTs) developing after sacrococcygeal teratoma (SCT) resection, and discussed the pathogenesis of sacrococcygeal YST. METHODS We retrospectively analyzed pediatric SGCT patients attending 10 Japanese institutions. RESULTS A total of 289 patients were eligible, of which 74.6% were girls. The mean age at surgery was 7.1months. There were 194 mature and 47 immature teratomas, and 48 YSTs. YST developed after SCT resection in 13 patients (5.4% of SCTs), and was detected between 5 and 30months after resection. At initial surgery, 9 of these 13 patients were neonates, 12 underwent gross complete resection with coccygectomy, and 9 had histologically mature teratoma without microscopic YST foci. Postoperative serum alpha-fetoprotein (AFP) levels were regularly examined in 11 patients. Intervals of AFP measurement≤4months helped to detect subclinical localized YSTs for resection. CONCLUSIONS The characteristics of SGCT in Japanese children were similar with those reported in Europe or the United States. YST developed after SCT resection not only in patients with previously reported risk factors. We recommend that patients undergo serum AFP monitoring every 3months for≥3years after SCT resection.

Primary cerebellar histiocytic sarcoma in a 17-month-old girl

The authors report on a case of histiocytic sarcoma (HS) in a pediatric patient presenting with a solitary tumor in the cerebellum, with the aim of providing insight into primary HS in the CNS, which is especially rare. A 17-month-old Japanese girl presented with a 2-week history of progressive gait disturbance. Brain MRI revealed a 4.7 × 4.3 × 4.3-cm well-demarcated solitary mass in the right hemisphere of the cerebellum, initially suggestive of medulloblastoma, ependymoma, or anaplastic astrocytoma. On intraoperative inspection the cerebellar tumor showed intensive dural attachment and was subtotally removed. Histological and immunohistochemical findings were consistent with HS. The patient subsequently received chemotherapy, and her preoperative neurological symptoms improved. Primary HS in the CNS usually demonstrates an aggressive clinical course and is currently considered to have a poor prognosis. The possibility of this rare tumor should be included in the differential diagnosis of localized cerebellar tumors in the pediatric age group.

Anaplastic sarcoma of the kidney with chromosomal abnormality: first report on cytogenetic findings.

We report a case of anaplastic sarcoma of the kidney (ASK) with cytogenetic findings. A 12-year-old Japanese girl presented with buttock pain and urinary incontinence. Radiological investigations revealed a right renal tumor with multiple distant metastases and multicystic thyroid tumor. She underwent radical right nephrectomy and subsequently received chemotherapy and radiation therapy. Histologically, the renal tumor demonstrated admixture of various types of mesenchymal elements: cellular spindle cells with anaplastic features, cartilage, and rhabdomyoblastic cells consistent with ASK. Chromosomal analysis revealed the karyotype of the tumor cells to be 46, XX, +8, -10, der (18) t (10; 18) (q21; p11.2). The thyroid tumor was removed later and diagnosed as adenomatous goiter. To our knowledge, this is the first case of ASK with chromosomal abnormality and may provide new insight into the molecular biologic basis of this rare renal tumor.

Unilateral glomerulocystic kidney disease associated with tuberous sclerosis complex in a neonate

We report a case of glomerular cystic kidney disease (GCKD) associated with tuberous sclerosis complex (TSC) in a neonate. The patient displayed progressive abdominal enlargement attributed to GCKD associated with TSC. After birth, the right kidney was resected because it compressed his liver and right lung, and possible malignancy could not be excluded. Macroscopically, the resected kidney was markedly enlarged, and histologically the kidney had numerous glomerular cysts accompanied by papillary epithelial growth. Notably, a small area of normal parenchyma was observed at the lower pole. The epithelial cells of the cysts displaying a papillary growth pattern were positive for mTOR, phosphorylated mTOR, and phosphorylated S6 ribosomal protein (p‐S6). The morphologically noncystic, normal‐looking tubular epithelium was also positive for p‐S6. These results imply that one more molecular event might be necessary for cyst formation in GCKD associated with TSC, in addition to the activation of mTOR signaling.

Specificity of splenopancreatic field abnormality in trisomy 13 syndrome: Macroscopic and histological analysis in 21 autopsy cases

Splenopancreatic field abnormalities were carefully examined macroscopically and microscopically in 21 trisomy 13 (TR13) subjects, and the results were compared with those of non‐TR13 control cases. Of the 21 TR13 subjects, 12 had intrapancreatic splenic tissue (IPST) and 17 had fusion of the pancreatic tail and splenic hilus and/or accessory spleen (FPS/FPAS). All 21 had IPST and/or FPS/FPAS. Five of 1060 controls (non‐TR13) had IPST, while two had FPS/FPAS. On histology the pancreata of TR13 subjects had intralobular ducts, with goblet cells (ILDGC) and microcysts (MC) in 17 and 18 subjects, respectively. All 21 TR13 subjects had ILDGC and/or MC. Two of 360 age‐matched controls (stillbirths and neonates) had ILDGC and nine had MC. IPST, FPS/FPAS, ILDGC, and MC were considered to be highly specific for TR13, and could therefore be useful in differentiating TR13 from other malformation diseases.