Mixed germ cell tumor and hemangioblastoma in the cerebellum: report of a rare coexistence.

We report a case of a cerebellar tumor consisting of a mixed germ cell tumor (GCT) and a hemangioblastoma. A 22-year-old man presented with myoclonus and cerebellar ataxia. Magnetic resonance imaging showed a tumor mass in the left cerebellar hemisphere. The tumor was totally removed, and the histological diagnosis was an undetermined neoplasm. Ten months later, the patient returned with cerebellar hemorrhage at the site of the previous tumor. An emergency craniotomy was performed, and a tumor mass adjacent to the hematoma was resected. Microscopic examination revealed a mixed GCT consisting of a germinoma, choriocarcinoma, and mature teratomatous component. An area of hemangioblastoma was also found in the same tumor mass. A retrospective examination of the histological sample from the first operation indicated a germinoma. A primary GCT of the posterior fossa is very rare, and there are no other reports of the coexistence of a GCT and a hemangioblastoma. A metastatic GCT lesion of extracranial origin should be considered when the intracranial GCT is non-germinomatous and arises in an unusual site. The most probable hypothesis for the histogenesis of this case was a hemangioblastoma complicated by a "tumor-to-tumor" metastatic lesion of testicular GCT with "burnout" of the primary site.

Cellular localization of sphingosine-1-phosphate receptor 1 expression in the human central nervous system.

Sphingosine-1-phosphate (S1P), a potent lipid mediator, transduces intracellular signals through the activation of S1P receptors (S1PRs). Although S1PRs have been shown to play an important role in the central nervous system (CNS), accurate localization and the function of S1PR1 in the human CNS are still unclear. In this study, we investigated the localization of S1PR1 in the human CNS of postmortem samples, using a rabbit polyclonal antibody, the specificity of which had been well defined. Immunohistochemical investigation of paraffin-embedded sections revealed diffuse granular staining of the gray matter. The signals of the gray matter were much stronger than those of the white matter. The immunohistochemical expression levels correlated well with the results of quantitative real-time RT-PCR-based analysis and Western blotting. Studies using double immunostaining and immunoelectron microscopy revealed that the antigen was strongly expressed in the membrane of the astrocytic foot processes of glia limitans and astrocytes with radial cytoplasm, but not distributed in neurons. In neurological disorders, hypertrophic astrocytes with strong expression of glial fibrillary acidic protein exhibited significantly decreased expression of S1PR1 in contrast to its strong expression in astrocytes forming fibrillary gliosis. These results indicate that S1PR1 is localized in astrocytes, and its expression level may change during the processes that occur after brain damage.

Rosai-Dorfman disease presenting as a solitary mediastinal mass.

Rosai-Dorfman disease (RDD) involving an extranodal site is a diagnostic challenge. Reported herein is the case of a 67-year-old man who presented with a solitary superior mediastinal mass. The lesion was clinically suspected of malignancy including lymphoma because of its high uptake during a (67)Ga-scintigram and (18)F-fluorodeoxyglucose-positron emission tomography. There was no evidence of spread of the disease. Histology of thoracoscopic biopsy specimens indicated granulomatous lesion with infiltration of lymphocytes, plasma cells, and histiocytes with lymphocytes engulfed in their cytoplasm. The lesion did not contain lymph node or thymic elements. On immunohistochemistry the histiocytes were positive for S-100 protein, CD68, and CD163 but were negative for CD1a. These findings suggested a diagnosis of RDD. Despite lack of intervention, the lesion remained almost the same size for 3 years. To the best of the authors' knowledge this is the first case of RDD presenting as a solitary mediastinal mass.

Pancreatic serous microcystic adenoma with extensive oncocytic change.

Herein is reported a case of pancreatic serous microcystic adenoma with extensive oncocytic change in a 73-year-old woman. Histologically the tumor consisted of numerous small cysts, separated by thin or broad fibrous septa. These cysts were lined with uniform cells having abundant eosinophilic granular cytoplasm, which was negatively or weakly stained with PAS. Immunohistochemically, the cyst-lining cells were positive for cytokeratin (CK) 7, CK19, MUC1, MUC6, alpha-inhibin, and neuron-specific enolase (NSE), and negative for CK8, CK20, MUC2, and MUC5AC; these immunoprofiles coincide with those of serous microcystic adenoma. Immunostaining with anti-mitochondrial antibody showed dense granular positivity in the cytoplasm, which suggested an oncocytic phenotype. Thus, this case is considered a variant of serous microcystic adenoma characterized by extensive oncocytic change. To the authors' knowledge no similar case has been reported in the literature. It may pose problems in the differential diagnosis of the cystic pancreatic tumors with oncocytic change, but can be diagnosed on histology and immunohistochemistry.

Sphingosine-1-phosphate receptor 1 is a useful adjunct for distinguishing vascular neoplasms from morphological mimics.

Sphingosine-1-phosphate receptor 1 (S1P(1)) has been shown to play an important role in the migration, proliferation, and survival of endothelial cells. S1P(1) of vascular and lymphatic endothelial cells can be detected by immunostaining of paraffin-embedded sections using a rabbit anti-S1P(1) antibody. In this study, to distinguish vascular tumors from histologic mimics using immunohistochemical means, we evaluated the expression of S1P(1) in a range of vascular tumors. S1P(1) expression was observed in eight of eight hemangiomas, four of four lymphangiomas, four of four epithelioid hemangioendotheliomas, three of three Kaposi's sarcomas, and 15 of 15 angiosarcomas with vasoformative, spindle, epithelioid, and undifferentiated features. Conventional analysis and use of a tissue microarray of soft tissue tumors revealed three of 21 liposarcomas to have weak cytoplasmic staining and one of five squamous cell carcinomas to have membranous staining in a very limited area among 115 nonvascular tumors including histological mimics of angiosarcoma such as undifferentiated carcinoma, melanoma, and epithelioid sarcoma. The sensitivity with regards to the angiosarcoma cases was equal to, or even exceeded in undifferentiated angiosarcoma, that of CD31. Based on this study, S1P(1) may be a useful adjunct to CD31 in cases where a vascular neoplasm requires a differential diagnosis.

Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma.

PURPOSE: According to the World Health Organization (WHO) classification of pulmonary large cell neuroendocrine carcinoma (LCNEC), one of the neuroendocrine tumors of the lung, is considered as a variant of non-small cell lung carcinoma. The objective of this study was to investigate the treatment strategy for LCNEC. METHODS: We retrospectively reviewed the clinical information of 12 patients with LCNEC. RESULTS: Three patients with stage I disease underwent curative resection but all relapsed within 20 months. One with stage IIA disease underwent non-curative resection received adjuvant chemoradiotherapy (cisplatin plus etoposide) and is well with no evidence of recurrence. Two with stage IIIB disease received concurrent chemoradiotherapy. Both achieved partial response (PR) but relapsed within 2 months. One elderly patient with stage IIIA disease received vinorelbine alone and did not respond. Of five patients with stage IV disease, three received platinum-based chemotherapy but no patient achieved PR. Of five patients with gefitinib as salvage therapy, one achieved PR. CONCLUSIONS: The prognosis of LCNEC is poor. To improve the outcome, we must evaluate the effectiveness of adjuvant or neoadjuvant therapy in patients with resectable disease. In addition, the evaluation of systemic and multimodality treatment strategies similar as in small cell lung cancer is worthy of consideration.

Intraductal oncocytic papillary neoplasm of the pancreas with celiac artery compression syndrome and a jejunal artery aneurysm: report of a case.

A 79-year-old woman presented with epigastralgia, and computed tomography showed a 3-cm multiloculated mass with a mural nodule in the head of the pancreas. Arteriography showed stenosis of the celiac artery and a saccular aneurysm, arising from the first jejunal artery. We made a preoperative diagnosis of intraductal papillary adenocarcinoma of the pancreatic head and performed a laparotomy. Transection of the median arcuate ligament failed to restore adequate hepatic blood flow, necessitating construction of celiac vascularization, achieved by a gastroduodenal to jejunal artery anastomosis. After ligation of the jejunal artery aneurysm, we performed a pylorus-preserving pancreaticoduodenectomy. Microscopically, the tumor had papillary intracystic growth, and was lined by plump cells with abundant eosinophilic cytoplasm, consistent with a diagnosis of intraductal oncocytic papillary neoplasm. We discuss this recently recognized entity of papillary neoplasm of the pancreas, and the importance of managing hepatic blood flow during pancreaticoduodenectomy in celiac artery compression syndrome.

[A case of lipomatous meningioma].

We present a case of a 55-year-old woman with intracranial lipomatous meningioma attached to the left sphenoid ridge. A CT showed a mass lesion partially with a hypodensity area in the left fronto-temporal lobe. On MRI, the mass lesion contained a hyperintensity portion on T1 weighted images, which changed to hypointensity on fat-suppressed-T1 images. Histological examinations demonstrated a transitional meningioma containing lipomatous portions. Immunohistochemical studies showed negative reactivity for epithelial membrane antigen (EMA) and positive reactivity for vimentin and S-100 in the areas with lipomaous foci. This pattern of reactivity was different from that of lipomatous meningiomas reported previously. Further examinations are needed concerning the origin of tumor cells in lipomatous meningiomas.

Pachydermoperiostosis associated with juvenile polyps of the stomach and gastric adenocarcinoma.

Pachydermoperiostosis (PDP) is a rare syndrome, and the presence of digital clubbing, radiographic periostosis, and coarse facial features are the main diagnostic criteria. Here, we report patient with the primary form of PDP in whom juvenile polyps and gastric cancer developed within 9 years of follow-up. A 27-year-old Japanese man, diagnosed as having the primary form of PDP at 14 years of age, was referred to our department for assessment of chronic anemia. On upper gastrointestinal endoscopic examination, multiple polypoid lesions with a huge polyp were found in the stomach, and biopsy findings indicated juvenile polyps, although no polypoid lesion had been present at the age of 18 years. Bleeding from these polyps was suspected, and endoscopic mucosal resection of the polypoid lesions was performed. Histology of the huge polyp showed hamartoma, adenoma, and adenocarcinoma in part. This is the first case report of the primary form of PDP associated with gastric cancer. In this patient, juvenile polyps and gastric cancer developed within 9 years of follow-up, indicating that the primary form of PDP may be a high risk factor for gastric cancer, and that periodical follow-up with upper gastrointestinal endoscopy is important.

Intraneural perineurioma involving the ulnar nerve.

Intraneural perineurioma is a rare peripheral nerve sheath tumor consisting of intraneural proliferation of neoplastic perineurial cells. Clinical and pathological findings of a perineurioma involving the ulnar nerve is presented. A 7-year-old girl presented with a 2 year history of weakness and atrophy of the right hand muscles. Physical examination and imaging study revealed a pea-sized tumor in the ulnar side of the right forearm. At surgery, a fusiform swelling of the ulnar nerve was found and an excisional biopsy of the lesion was performed. Light microscopy revealed numerous whorls consisting of concentric layers of spindle cells encircling the nerve fibers. The proliferating cells were immunoreactive for vimentin, epithelial membrane antigen and glucose transporter protein 1 (Glut1), but negative for S-100 protein and CD34. Ultrastructural examination revealed features of perineurial cell differentiation. The current study suggests that Glut1 is a useful marker of intraneural perineurioma.

Long-term effect of gefitinib (ZD1839) on squamous cell carcinoma of the lung.

This case report describes the effects of long-term treatment with the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib ('Iressa', ZD1839) on a patient with squamous cell carcinoma of the lung. Gefitinib is an orally active agent that blocks signal transduction pathways implicated in the proliferation and survival of cancer cells and host-dependent processes that promote tumor growth. A 62-year-old Japanese man with a history of heavy smoking was diagnosed with squamous cell carcinoma of the lung, clinical stage IIIB (T4N3M0), in August 2000. He received two cycles of cisplatin-based chemotherapy and subsequently underwent left upper lobectomy followed by thoracic radiotherapy. After these treatments, he underwent partial lobectomy and pneumonectomy because of disease recurrence. In June 2002, he started treatment with gefitinib 250 mg/day orally because of mediastinal lymph node recurrence and an elevated serum cytokeratin 19 fragment (CYFRA) level. As a result, the mediastinal lymph node markedly regressed and the serum CYFRA level became normalized. Although he experienced recurrence three times during the 18 months prior to treatment with gefitinib, recurrence has not been experienced in the 13 months since the start of gefitinib treatment, while tolerability has been acceptable.

Amplification of MYCL in Atypical Ewing Tumor. Analysis of Metaphase and Microarray Comparative Genomic Hybridization.

A 20-year-old man developed a soft tissue mass in his right upper arm and, 3 months later, was referred to our hospital. The tumor cells showed brisk mitotic activity and a large amount of cytoplasmic glycogen was demonstrated with periodic acid Schiff stain. A diagnosis of atypical Ewing sarcoma was made. Chemotherapy according to the VACA protocol, comprising vincristine, actinomycin D, cyclophosphamide and doxorubicin was started. The chemotherapy was effective and a limb salvage procedure was performed by implantation of an autoclaved bone after wide tumor excision. During the postoperative chemotherapy, a local recurrence and multiple metastases developed, and the patient died due to disease progression. Fourteen years later, this tumor sample, preserved in a deep-freeze, was analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) to detect the fusion gene. This tumor had an EWS exon 7 to FLI1 exon 6 fusion transcript. Moreover, metaphase and microarray comparative genomic hybridization (CGH) was done to detect chromosomal instabilities. Many gains and losses were noted on metaphase CGH, and MYCL amplification was identified on microarray CGH.

Expression of CD34 antigen in testicular mixed germ cell tumor.

The expression of CD34 was investigated in 14 cases of testicular mixed germ cell tumor to elucidate the relationship between its expression and histological patterns. Seven of 12 yolk sac tumor components were focally immunoreactive for anti-CD34 antibody. Of these, five showed focal but intense CD34 staining, while the remaining two tumors showed weak staining in small clusters or isolated tumor cells. Positive immunostaining for CD34 was seen predominantly in solid and reticular patterns of the yolk sac tumor components. Seminoma, embryonal carcinoma, and choriocarcinoma components were invariably negative for CD34. If present, immunoreactivity for CD34 in yolk sac tumors is focal and variable, but useful for the distinction from other germ cell tumors.

Expression of thyroid transcription factor-1 in strumal carcinoid and struma ovarii: an immunohistochemical study.

Strumal carcinoid is an ovarian teratoma composed of thyroid tissue and carcinoid, intimately admixed in variable proportions. To further elucidate the histogenesis of strumal carcinoid, the expression pattern of thyroid transcription factor-1 (TTF-1) was evaluated in two cases of strumal carcinoid using immunohistochemical techniques. TTF-1 is a nuclear transcription protein that is selectively expressed in the thyroid and respiratory epithelium, and is thought to be expressed specifically in pulmonary and thyroid neoplasms. While the follicular lining cells of the strumal carcinoid showed positive staining for TTF-1, the carcinoid element was, for the most part, negative. These results confirm that TTF-1 is expressed in the thyroidal element of ovarian teratomas and also provide further evidence that the carcinoid component of the strumal carcinoid bears no relation to thyroidal differentiation.

Spontaneous regression of metastatic endometrial stromal sarcoma.

Spontaneous regression of malignancy is rare and there appear to be no reports of spontaneous regression of endometrial stromal sarcoma. We report a rare case of metastatic endometrial stromal sarcoma that regressed spontaneously. A 58-year-old woman was admitted to hospital in January 1996 when her chest radiograph showed multiple nodular shadows in the left lower lung field. Computed tomography of the chest revealed bilateral nodules. Segmentectomy of the left lower lobe was performed by thoracoscopy. She had a past history of uterine myoma with metrorrhagia for which she had undergone a hystero-oophorectomy 10 years earlier. She also had a vaginal polyp removed 1 year earlier. The lung pathology was studied and the surgical specimens of the uterus and vagina were re-examined. The diagnosis was endometrial stromal sarcoma primarily arising in the uterus. The vaginal polyp and the pulmonary nodules were considered to be metastases. Samples of lung and vaginal tissues were positive for both estrogen and progesterone receptors. The patient was discharged without treatment in February 1996 and followed up in the outpatient clinic. The tumor shadow measuring 2 mm in diameter on admission was enlarged to 4 mm in diameter 1 year later. Surprisingly, spontaneous regression of the lung disease occurred at 33 months, the tumor size decreasing to 2 mm in diameter and to 1 mm at 46 months. No evidence of tumor enlargement was detected at the last follow-up in July 2001. Although the precise mechanism of tumor regression is unknown, metastatic endometrial stromal sarcoma may spontaneously regress.