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The histology of basaloid squamous cell carcinoma (BSCC) can resemble that of adenoid cystic carcinoma (AdCC). Herein, we report two cases of BSCC with adenoid cystic-like features (BSCC-AdC). We collected cases of AdCC and BSCC of the head and neck region, extracted two cases with unusual histology, and reexamined them histologically and immunohistochemically. Case 1 involved an 81-year-old Japanese male, who had an elastic-hard mass on the left side of his tongue, and a biopsy examination suggested AdCC. Case 2 involved a 63-year-old Japanese male, who had a polypoid mass on his right hypopharynx. He was diagnosed with AdCC with high-grade transformation. Histologically, atypical cells in a myxoid stroma, which exhibited trabecular, nest-like, and/or cribriform growth patterns, and necrosis were observed in both cases. Case 2 displayed more marked cellular atypia than Case 1. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin 5/6, p63/p40, SRY-related HMG-box 10 and Ki-67, but negative for other myoepithelial markers and p16. Finally, both cases were rediagnosed as BSCC-AdC. It is known that esophageal BSCC displays adenoid cystic-like features, and BSCC-AdC also sometimes occurs in the head and neck region. Clinicians should carefully differentiate BSCC-AdC from AdCC of the minor salivary glands and human papillomavirus-related carcinoma.

The recent recognition of concept of perivascular myoid cell (PMC) phenotype and perivascular epithelioid cell (PEC) phenotype has changed the concept of angiogenic tumors, in particular "hemangioperycytoma" (HPC)-like tumors. The PMC concept has yielded myopericytoma, myofibroma, myofibromatosis, angioleiomyoma, and glomus tumors, while the PEC concept that shows melanocytic lineage has given rise to PEComa, clear cell sugar tumors, angiomyolipoma, and lymphangiomyomatosis. Here, the author reports a case of myopericytoma of soft tissue (thigh) occurring in a 47-year-old man. The patient had noticed the thigh tumor 4years before, and was admitted. The tumor was located in subcutaneous tissue, was encapsulated, and measured 4×3×3cm. Total excision was performed. Grossly, the tumor is a soft reddish encapsulated tumor with very well demarcation. Histologically, the tumor showed typical HPC-like features with focal nodular proliferation of HPC-like tumor cells. Immunohistochemically, the vasculatures were positive for vimentin, CD31, CD34, and factor VIII-related antigen. In contrast, the HPC-like tumor cells were positive for vimentin, α-smooth muscle antigen, h-caldesmon, bcl-2, and factor XIIIa, but negative for cytokeratins, desmin, CD31, CD34, factor VIII-related antigen, S100 protein, melanosome, CD99, and KIT. Ki-67 labeling was 15%, and p53 was mildly positive. The overall features were those of myopericytoma. The patient is now alive without recurrence 5years after the operation. A brief literature review and differential diagnosis were made.

Herein reported is an extremely rare case of primary MALT lymphoma of cerebral parenchyma. A 79-year-old man presented with paresis. Imaging modalities identified a tumor measuring 3cm in diameter in right cerebral parenchyma. An operation completely resected the tumor. Macroscopically, the tumor was well defined, but showed mild infiltrative features. Histologically, the tumor showed proliferation of small atypical lymphocytes separated by fibrous septae with AL amyloid depositions. No apparent plasma cell differentiation was seen. The tumor cells showed monotonous appearances with hyperchromatic nuclei but without nucleoli and nuclear indentations. Immunoblastic cells were scattered. Immunohistochemically, tumor cells were positive for vimentin, CD45, CD20, CD79α, bcl-2, CD3 (focal), CD45RO (focal), CD5 (focal), CD10, CD23, bcl-6, CD138, p53, and Ki-67 (labeling=27%). The immunoblastic cells were positive for CD30. The lymphoid cells were negative for Epstein–Barr virus (EBV)-related molecules of EBV latent membrane protein-1 (LMP-1) and EBV early RNAs (EBER). They were also negative for cytokeratins AE 1/3 and CAM5.2, cyclin D1, CD34, GFAP, α-smooth muscle actin, and S100 protein. Because of the heterogeneity of tumor cells and positive AL amyloid deposition, the author diagnosed it as primary MALT lymphoma. The patient is now free from tumors. Differential diagnosis was discussed.

Primary mucinous adenocarcinoma (MA) of vermiform appendix is extremely rare; only three cases have been reported in the English literature. A 77-year-old man presented with abdominal pain, and was diagnosed with acute appendicitis. Appendectomy was performed. The resected appendix showed submucosal swelling measuring 0.7×0.6×0.6cm in the tip of appendix. The appendix showed inflammation and numerous diverticuloses. Microscopically, the submucosal swelling was a mucin lake in which adenocarcinoma cells were floating. The adenocarcinoma cells were MA in 80% and signet-ring cell carcinoma in 20%. The carcinoma cells were located in the submucosa, muscular layer and subserosa, sparing the mucosa. No apparent lymphovascular permeation was seen. The surgical margins were negative for tumor cells. The non-tumorous appendix shows numerous diverticulosis, diverticulitis, and appendicitis. Immunohistochemically, the tumor cells were positive for CK CAM5.2, CK AE1/3, CK8, CK18, CK19, CK20, EMA, CEA, CA19-9, MUC1, MUC2, MUC5AC, MUC6, NCAM, p53 and Ki-67 (labeling index=23%). The tumor cells were negative for CK34BE12, CD5, CK6, CK7, NSE, chromogranin, synaptophysin, CA125, KIT, and PDGFRA. No metastasis has been seen 2.5years after the operation.

Mixed tumor of soft tissue is extremely rare; only 15 cases have been reported in English literature. A 56-year-old man presented with a tumor in right arm. Physical examination showed a tumor measuring 3 × 3 × 3 cm of deep portion of right arm. MRI showed a well-defined deep tumor measuring 3 × 3 × 4 cm of arm next to fascia. The tumor was resected, and it was found that the tumor is located in deep subcutaneous tissue outside the fascia. Histologically, the tumor was well-defined and contained a fibrous capsule. The tumor cells showed no significant nuclear atypia. The tumor was composed of epithelial, myoepithelial, and stromal elements. The epithelial element formed tubules, and myoepithelial element showed solid nests and periepithelial linings. The epithelial element showed frequent apocrine features including apocrine snouts. The stromal element was composed of cartilage and myxoid tissues. Immunohistochemically, the epithelial element was positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK34BE12, CK7, CK8, CK18, CK19, EMA, CEA, CD56, p53, and Ki-67 (labeling = 80%), but negative for CK5/6, CK14, CK20, vimentin, p63, S100 protein, CD10, CD34, ASMA, CD68, myoglobin, bcl-2, BMP-2, TGF-β1, CDK-4, and MDM2. The myoepithelial element was positive for CK AE1/3, CK CAM5.2, CK34BE12, CK5/6, CK7, CK8, CK14, CK18, p63, vimentin, CD10, S100 protein, bcl-2, p53, and Ki-67 (labeling = 20%), but negative for CK19, CK20, EMA, CEA, CD34, ASMA, CD68, CD56, myoglobin, BMP-2, TGF-β1, CDK-4 and MDM2. The stromal element was positive for vimentin, S100 protein (cartilage), and Ki-67 (labeling = 6%), but negative for other antigens examined including bcl-2, BMP-2, TGF-β1, CDK-4 and MDM2. No findings of metastasis, invasion, and recurrence were recognized clinically. The author speculates that the current mixed tumor was derived from misplaced apocrine glands in the deep soft tissue.

The aim of the study was to investigate nerve fibers (NF) in human fetal livers. An immunohistochemical study was performed. NF were classified into portal tract innervation (PoI) and parenchymal innervation (PaI). The hilum area showed many Pol NF at 7 GW, and NF increased with gestational week (GW). Direct innervations to biliary epithelium were recognized. In large portal tracts, a few NCAM-positive mesenchymal cells were seen at 8 GW and many mesenchymal cells were noted around 12 GW. Apparent NF emerged around 15 GW, and NF increased with GW. Many NF plexuses were seen in 30-40 GW. In small portal tracts, no NF were seen in 7-10 GW. A few NCAM-positive mesenchymal cells emerged in 11 GW, and they increased thereafter. Apparent NF were seen around 20 GW and NF increased with GW. At term (40 GW), PoI NF were still immature. Ductal plate (DP) was positive for NCAM, NSE, chromogranin and synaptophysin, and direct innervations to DP were seen. The direct innervations to developing bile ducts and peribiliary glands were also seen. PaI NF were first seen at 21 GW and was consistent until 40 GW in which a few NF were seen in PaI. These observations suggest that PoI NF arise from committed portal mesenchyme. PaI NF are very immature at 40 GW. There are direct innervations to bile ducts, peribiliary glands, portal veins, hepatic arteries, and DP.

Basaloid squamous cell carcinoma of esophagus (BSCC-E) is rare. This case report is the first demonstrating KIT protein expression of BSCC-E. A 74-year-old man presented with dysphagia. Endoscopy revealed a polypoid tumor (2×2×2.5cm) with a stalk in cervical esophagus. Biopsy showed squamous cell carcinoma with undifferentiated areas. An endoscopic submucosal dissection (ESD) was performed. Grossly, it was solid tumor with white cut surface. Histologically, the tumor was hypercellular carcinoma consisting of solid areas of island. The tumor cells were composed of basaloid malignant cells with hyperchromatic nuclei, scant cytoplasm, and basophilic cytoplasm. Many mitotic figures were recognized. Foci of comedonecrosis were scattered. Areas of squamous and glandular differentiations were scattered. Immunohistochemically, the tumor cells were positive for pancytokeratin (PCK) CAM5.2, PCK AE1/3, cytokeratin (CK) 7, KIT, CEA, CA19-9, EMA, Ki-67 (labeling index=80%). The tumor cells were negative for CK20, PDGFRA, NSE, vimentin, estrogen receptor, p53 protein, chromogranin, synaptophysin, CD56, and TTF-1.

Background: Nothing is known about huge clusters (HC) of embryonic stem cells (ESC) in human fetal organs (HFO). Aim: To know the status of HC-ESC in HFO. Methods: Morphology and immunohistochemistry (IHC) in 32 HFO of 7–40 gestational weeks (GW). Results: HC-ESC were seen in many HFO including central nervous system, spinal cords, spine, soft tissue, bone, skin, thyroid, lung, liver, pancreas, gall bladder, extrahepatic bile duct, adrenal, kidney, bladder, foregut, midgut, hindgut, female and male genital organs, and neurons. HC-ESC's were composed of two populations depending on constituting cells. One were large cells with ample acidophilic cytoplasms with vesicular nuclei and nucleoli. The other were small cells with scant cytoplasm with hyperchromatic nuclei without nucleoli, resembling lymphocytes. The HC-ESC were frequently showed neuronal differentiation. HC-ESC were positive for NCAM, synaptophysin, NSE, chromogranin, PDGFRA, AFP, ErbB2, bcl-2, KIT, MET. They were negative for CD45, CD3, CD20, EMA, CEA, CA19-9, cytokeratin (CK) 7, CK8, CK18, CK19, MUC1, MUC2, MUC5AC, and MUC6. The mean Ki-67 labeling index (LI) was 13% ± 7%. HC-ESC showed a little glycogen but lacked mucins. These HC-ESC were seen in 7–25 GW, and they were rarely seen in 26–40 GW. Conclusions: The morphology, IHC, and ontogeny of HC-ESC were described. Microsc. Res. Tech. 77:825–831, 2014. © 2014 Wiley Periodicals, Inc.

Background: The fetal development of extrahepatic bile ducts (EBD) is unkown. Materials and Methods: Development of EBD was examined by immunohistochemistry in 16 fetuses of 7–40 gestational week (GW). Gall bladder (GB) was not investigated. Results: At seven GW, a hepato-pancreatic bud (HPB) was seen near the hepatic hilus. At eight GW, embryonic EBD, GB and pacreas developed from HPB. Portal veins (PV) and hepatic arteries (HAs) were present in EBD at eight GW. Liver parenchyma was already present in seven GW. At eight GW, EBD at porta hepatis (PH) was already established; PH EBD was derived from ductal plate (DP). The distal and middle EBD gradually develeped and took shape of EBD at nine GW. In PH, cystic and hepatic ducts developed from DP at eight GW. EBD developed further, accompanying many nerve fibers (NF) at PH and distal and middle EBD. Apparent PV and HA were seen around 12 GW. Around 20 GW, HA and capillaries proliferated, giving rise to peribiliary capillary plexus (PCP) in all parts of EBD. EBD grew gradually further, and around 30 GW extrahepatic peribiliary glands (EPG) emerged from EBD but not from cystic duct. Around 36 GW, exocrine pancreatic acinar cells emerged from remodeled DP at PH. At term (40 GW), EBD was established but was as yet immature. Numerous NF were present around EBD. Histochemically, EBD epithelium had no mucins at 7–12 GW but contained neutral and acidic mucins at 23–40 GW. EPG had abundant neutral and acidic mucins. Immunohistochemically, alpha-fetoprotein (AFP) was consistently positive in the epithelial and mesenychyma. The NF and muscles of HPB present at seven GW were positive for neural cell adhesion molecule (NCAM), neuron-specific enolase (NSE), platelet-derived growth factor receptor-α (PDGFRA), and KIT, but they disappeared in nine GW. Expressions of cytokeratin (CK) seven and CK19 in EBD and EPG were slight or none, while expression of CK8 was moderate, and that of CK18 was strong. NF were positive for NCAM, NSE, synaptophysin, and chromogranin, and PDGFRA. MUC1 and MUC6 apomucins were noted in EBD and EPG. EPG contained numerous endocrine cells positive for chromogranin, synaptophysin, NCAM and NSE. A few endocrine cells positive for these antigens were seen in EBD. Numeous KIT-positive stem cells (SC) were seen in PH, EBD, PV, HA, PCP, and EPG. NCAM-positive and bcl-2-positive SC were also located in these structures. Epithelial cells of EBD and EPG showed expressions of MET, PDGFRA, CA19-9, MUC1, MUC2, MUC6, KIT, bcl-2, and ErbB2. No expressions of HepPar1, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA) were noted. Conclusions: Although the findings have limitatios because this study of humans are descriptive one, the present data suggest that the processes of the development and differentiation of EBD system may be associated with EBD SC, CK prolifes, SFC/KIT signaling, HGF/MET signaling, PDGRa/PDGFRA signaling, fibroblast growth factor/ErbB2 signaling, neuroendocrine lineage, NF differentiation, pancreatic aninar cell differentiation, PCP differentiation, MUC apomucins differentiation, and expressions of AFP and CA19-9. HepPar1, EMA and CEA were not involved in them. Microsc. Res. Tech. 77:832–840, 2014. © 2014 Wiley Periodicals, Inc.

The author herein reports a case of multiple verrucous carcinomas (VCs) of the left lower gingiva. A 78-year-old man was admitted to our hospital because of gingival tumor. A biopsy revealed severe dysplasia. Surgical resection was performed. Grossly, there were three verrucous lesions (25, 20, 10 mm) in the left lower gingiva. Histologically, 2 tumors (4, 2 mm) were found in addition to the grossly visible 3 tumors. All the 5 tumors were VCs. The tumors showed verrucous and papillary proliferation of squamous epithelium with little cellular atypia. No invasive features were recognized. The dermis showed lymphocytic infiltration. The surrounding mucosa showed many broad foci of squamous cell carcinoma in situ and severe dysplasia (high grade intraepithelial neoplasm). Gradual merges between the VCs and squamous cell carcinoma in situ or severe dysplasia were frequently recognized. Immunohistochemically, the VC tumor cells and squamous lesions were negative for human papilloma virus antigens. P53 protein was expressed in all the VCs and squamous epithelial lesions: it was accentuated in the basal and suprabasal cells of VC. Ki-67 antigen was also expressed in the 5 VCs and in the squamous lesion, and Ki-67 labeling index ranged from 8 to 16 % in VC and from 37 to 62 % in the squamous lesions. These data support the multicentric nature of VC and that the severe dysplasia–carcinoma in situ sequence have been proposed in the etiology of VC.

The author reports an extremely rare case of atypical carcinoid of the pleura expressing KIT. An 81-year-old Japanese man with emphysema was found to have a mass (3×3×2 cm) in the left parietal pleura by various imaging modalities. Video-assisted tumorectomy was performed, but could not excise it completely. Histologically, the tumor was composed of atypical cells arranged in trabecular, ribbon-like, and rosette patterns. Mitotic figures and necrosis were present. The tumor cells were argyrophil. Immunohistochemically, the tumor cells were positive for pancytokeratins, cytokeratin (CK) 18, chromogranin (focal), p53, KIT, and Ki67 (labeling=17%). In contrast, the tumor cells were negative for CK5/6, CK7, CK19, CK20, CK34βE12, epithelial membrane antigen, vimentin, S100-protein, α-smooth muscle actin, desmin, CEA, TTF-1, CDX-2, AFP, HepPar-1, synaptophysin, CD56, CA19-9, CD15, neuron specific enolase, serotonin, CD34, platelet-derived growth factor-α, calretinin, thrombomodulin, WT-1, B72.3, and D2-40. The pathologic diagnosis was atypical carcinoid of the pleura. The patient was examined by whole body computed tomography, magnetic resonance imaging, and positron emission tomography, but there were no tumors other than the pleural tumor. Endoscopic examinations including upper and lower gastrointestinal tract revealed no tumors. Therefore, the pleural tumor was thought to be primary. Ten months later, the patient developed metastatic lesions in the vertebular and femoral bones, and died of respiratory failure. Autopsy was not performed. To the best of the author's knowledge, there are no cases of primary carcinoid in the pleura in the English literature. This case is also interesting in that the atypical carcinoid expressed KIT.

Obvious neuroendocrine differentiation has not been reported in glomus tumor. The author herein reports a malignant glomus tumor of the foot showing obvious neuroendocrine differentiation. A 63-year-old woman presented with tumor of the left foot. The tumor was superficially seated, and located in the dermis. It was completely resected with wide margins. It measured 0.7 × 0.7 × 0.6 cm. Microscopically, the tumor was composed of atypical epithelioid cells located around blood vessel-like structures. The epithelioid cells showed relatively clear cytoplasm and severe cellular atypia, and resembled basal cell carcinoma. Focal areas of squamoid differentiation, carcinoid patterns, and neural differentiations were seen. There was no necrosis or atypical mitosis. However, mitotic figures were seen in 16 per 50 high-power-fields (HPF). The hematoxylin and eosin (HE) diagnosis was basosquamous carcinoma. Immunohistochemically, the tumor cells were strongly positive for vimentin, -smooth muscle actin, and neuron-specific enolase. The tumor was focally positive for NCAM, synaptophysin and chromogranin. The blood vessel-like structures had a layer of CD31- and CD34-positive endothelial cells. Tp53 was positive and the Ki-67 labeling index was 23%. The tumor cells were negative for cytokeratin (CK) AE1/3, CK CAM5.2, CK5, CK6, CK7, CK8, CK14, CK18, CK19, CK20, p63, EMA, CEA, CA19-9, desmin, myoglobin, HMB-45, Melan-A, S100 protein, MUC1, MUC2, MUC5AC, and MUC6. Taken together with HE histology, the tumor was labeled as malignant glomus tumor with neuronal differentiation, based on the classification system of Folpe et al. The post-pathological diagnosis whole body examination using CT, MRI, PET, and endoscopies identified no tumors. The patient is now free from tumor and healthy 18 months after the resection.

Mesenchymal tumors (MT) of the gastrointestinal (GI) tract are relatively common conditions, the majority being gastrointestinal stromal tumors (GIST) [1–4]. The classification system of MTof the GI tract changed around 2000 when gain-offunction mutations of KIT and PDGFRA were for the first time found [1, 2]. Since then, the classification procedure of MTof the GI tract has been performed by immunohistochemical (IHC) findings of KIT, CD34, S100 protein, and myogenic proteins [3]. Therefore, studies of MTof the GI tract before around 2006 lost their significance. Schwannoma and leiomyoma of the colon are relatively rare, and circa 90 cases and circa 200 cases have been reported in the world literature, respectively. Since the diagnostic criteria of GIST and some MT were established only recently around 2006 [3], the incidence/prevalence of MT in the GI tract has not been evaluated and therefore unknown; a PubMed search revealed no such studies. Non-GIST MT appears very rare.

Clear cell adenocarcinoma of the urinary bladder is rare. A 73-year-old woman presented with chronic renal and cardiac failure. Blood tests showed elevated carcinoembryonic antigen and CA19-9 levels. Imaging techniques showed bilateral hydronephrosis and hydroureter. Cystoscopy showed a bladder tumor, and the biopsy showed malignant cells. The patient died 4 months later. Autopsy showed an elevated tumor of the bladder. Metastases to the liver, lungs, adrenal glands, spleen and bones were observed. The kidney showed chronic active pyelonephritis with hydronephrosis. The cause of death was chronic renal and cardiac failure and/or carcinomatosis. Histologically, the bladder tumor consisted of malignant clear cells arranged in solid nests and tubules. Histochemical stains for glycogen and mucins were negative. Metastases also showed similar histology. Immunohistochemically, the tumor cells were positive for carcinoembryonic antigen, CA19-9, CA125, CD10, pancytokeratins (AE1/3, CAM5.2), cytokeratin (CK) 34βE12, CK7, CK8, CK18, CK19, EMA, MUC1, p53, and Ki-67 (labeling=40%). They were negative for CK5/6, CK14, CK20, estrogen receptor, progesterone receptor, α-methylacyl-CoA-racemase, p63, CDX2, MUC2, MUC5AC, MUC6, CD45, CD34, vimentin, neuron-specific enolase, S100 protein, desmin, HMB45, AFP, α-smooth muscle actin, MDM2, HER2/neu, synaptophysin, and CD56. Metastases showed the same immunohistochemical findings.

Only 5 cases of follicular lymphoma (FL) have been reported in the prostate. A 68-year-old man presented with dysuria. Laboratory data did not indicate malignancy in the prostate with serums PSA of 4.6 ng/ml. Imaging techniques identified no tumors and lympho-adenopathy other than the prostatic enlargement. The patient was clinically diagnosed as prostatic hyperplasia, and trans-urethral resection of prostate (TURP) (65 g) was done. Histologically, the TURP-specimens showed severe nodular proliferation of atypical small lymphocytes consisting of small centrocytic lymphocytes and large centroblastic lymphocytes, the number of the latter being 2/HPF. Immunohistochemically, the tumor cells and nodular areas were positive for CD45, CD20, CD79a, bcl-2, bcl-6, and CD10. They were negative for pan-cytokeratin (AE1/3, CAM5.2), CD3, CD45RO, CD56, PSA, chromogranin-A, synaptophysin, NSE, CD138, CD15, CD30 and cyclin D1. No significant number of plasma cells were seen by immunohistochemistry for light chains and CD138. A pathological diagnosis of primary FL (grade 1) of the prostate was made. No tumors were identified by various imaging techniques, and the prostatic FL was diagnosed as primary. The patient underwent low-dose R-CHOP chemotherapy and focal radiation, probably resulting in complete remission. No recurrence has been found 5 months after the diagnosis.

Primary sarcomatoid squamous cell carcinoma (S-SCC) of pharynx is a very rare tumor. A 77-year-old woman presented with sore throat. Laryngoscope revealed an infiltrating tumor of lower pharynx. The tumor was ulcerated and measured 3 cm × 4 cm × 3 cm. The tumor was invasive and involved the surrounding tissues. Biopsies showed sarcomatous malignant spindle cell proliferation as well as invasive well-differentiated squamous cell carcinoma (SCC). The former occupied 80% and the latter 20%. Gradual transitions between malignant spindle cells and SCC were frequently seen. The histological diagnosis was S-SCC. Immunohistochemically (the results are shown in Table 1), the tumor cells were positive for vimentin, cytokeratin (CK) AE1/3, CK CAM5.2, CK WSS, CK KL-1, CK MNF-15, CK5, CK6, CK7, CK8, CK 18, CK19, p53 and Ki67 (labeling index = 65%), but negative for CK34BE12, CK20, EMA, S100 protein, NSE, NCAM, synaptophysin, chromogranin, desmin, -smooth muscle actin, smooth muscle actin (HHF-35), h-caldemon, CD31, factor VIII-related antigen, CD34, HMB45, KIT, PDGFRA, CA19-9, CEA, bcl-2, CD3, CD20, CD45, CD138, myoglobin, HPV, and EBER. The author’s diagnosis was S-SCC. The patient received chemotherapy and radiation, and is now in complete remission 3 years after the diagnosis.

Schneiderian papilloma (SP) is classified into three types: inverted, oncocytic, and exophytic. Malignant transformation occurs in 10% of SP; most are inverted and oncocytic types. Malignant transformation of polypoid exophytic SP is exceptional; only two cases have been reported in the English literature. A 58-year-old man consulted our hospital because of nasal obstruction. Nasal endoscopy and imaging modalities showed a polyp in the right nasal cavity. Biopsy findings showed compatibility with SP. However, since fludeoxyglucose positron emission tomography (FDG-PET) showed signals, polypectomy was performed. Grossly, the polyp was reddish white and measured 2 cm. Histologically, the polyp consisted of a non-invasive squamous cell carcinoma (SCC) component (70%), a mature squamous component (20%), and Schneiderian epithelium (10%). Vague koilocytosis was present in the SCC component. The three components were arranged in an exophytic papillary pattern. Immunohistochemically, the non-invasive SCC component was positive for cytokeratins (AE1/3, CAM5.2, CK5/6), p63, p53, and Ki67 (labeling 50%). The mature squamous component was positive for cytokeratins (AE1/3, CAM5.2 and CK5/6), p63, and Ki67 (labeling 6%). The Schneiderian component was positive for cytokeratins (AE1/3, CAM5.2, and CK5/6), p63, and Ki-67 (labeling 4%). The tumor was HPV negative in the three components. The polyp was diagnosed as exophytic Schneiderian carcinoma arising from exophytic SP. The patient is now free from tumor 4 years after the operation.

Protein expression and gene mutational status of KIT and PDGFRA were investigated in formalin-fixed, paraffin-embedded specimens of 14 ipsilateral testicular seminomas. The analysis was performed by ordinary immunohistochemistry and polymerase chain reaction-direct sequencing methods. The genetic analysis was performed in exons 9, 11, 13, and 17 of KIT gene and in exons 12 and 18 of PDGFRA gene. Six point mutations of 5 types of KIT gene were recognized in 5 (36%) cases; exon 17 around codon 816 was a hotspot. The mutation sites of KIT gene were as follows: codon 557 in exon 11 (1 case), codon 816 in exon 17 (3 cases), codon 820 in exon 17 (1 case), and codon 822 in exon 17 (1 case). One patient showed multiple mutations of KIT gene. Immunoreactive KIT was recognized in 13 (93%) cases; the expression was strong in the 5 KIT mutation-positive cases, but variable or none in the 9 KIT mutation-negative cases. No PDGFRA gene mutations were observed in all the 14 cases. PDGFRA protein expression was weakly recognized in 12 cases but none in the remaining 2 cases. These data suggest, in testicular seminomas, that 36% of ipsilateral testicular seminomas have KIT mutations, KIT mutations are frequent around codon 816 of exon 17, multiple KIT mutations may be present, KIT expression is stronger in KIT mutation-positive cases than negative cases, PDGFRA gene mutations are absent, and PDGFRA protein is weakly expressed.

Sinonasal-type hemangiopericytoma is a very rare disease. A 64-year-old man was admitted to our hospital because of nasal obstruction. Nasal endoscopy showed a polyp in the right nasal cavity. Imaging modalities including CT and MRI revealed polypoid tumors in the right nasal cavity and right sphenoid sinus. Excision of the tumors was performed. Macroscopically, the nasal tumor was reddish and focally cystic, and the tumor of the sphenoid sinus was reddish and solid. Microscopically, round and polygonal cells were seen to proliferate monotonously in a medullary fashion. Each tumor cell had a vesicular nucleus and amphophilic cytoplasm. The cellularity was high and mitotic figures were recognized in 6 per 10 high-power fields. Many thin-walled vessels were embedded within the tumor. No collagenization was recognized. A silver stain showed that fine argyrophilic fibers encased individual cells and a few cell nests. Mild invasion into the surrounding tissue was recognized in focal areas. The tumor showed focal cystic and hemorrhagic changes. Immunohistochemically, the tumor cells were positive for vimentin, bcl-2 and factor XIIIa, and negative for cytokeratins, epithelial membrane antigen, CD34, desmin, α-smooth muscle antigen, myoglobin, myogenin, CD31, KIT, p53 protein, CD99, and factor VIII-related antigen. Ki-67 labeling was 17%. The pathological diagnosis was low-grade malignant sinonasal-type hemangiopericytoma. The patient was followed up, but no recurrence has been seen 4 years after the operation.

Although a few cases of sinonasal carcinoma with focal sarcomatous differentiation have been reported, pure sarcomatoid carcinoma has not been reported in the English literature. Imaging studies and gross inspection in a 60-year-old man with left-sided face pain revealed a mass in the left maxillary sinus and nasal cavity. A large incisional biopsy specimen from the nasal cavity revealed proliferation of malignant spindle and round cells with a malignant fibrous histiocytoma (MFH) pattern. Tumor giant cells were scattered, and there were areas of a vague storiform pattern. Mitotic figures were numerous. Carcinomatous component was not recognized. The histologic diagnosis was storiform-pleomorphic MFH. Tumor cells were positive for pancytokeratins AE1/3, KL-1, and CAM5.2 and cytokeratin (CK) 18, vimentin, CD68, p53, Ki-67 (labeling, 90%), α1-antitrypsin, and α1-antichymotrypsin and negative for pancytokeratin WSS, CK 34βE14, CK7, CK8, CK14, CK19, CK20, epithelial membrane antigen, S-100 protein, desmin, α-smooth muscle actin, CD34, HMB45, chromogranin, synaptophysin, myoglobin, CD45, CD30, and CD15. Because keratins were positive in tumor cells, a diagnosis of sarcomatoid carcinoma simulating MFH was made. The patient was treated with chemoradiation without significant effect and died 9 months after initial examination.

Primary small cell carcinoma of the prostate is extremely rare. Herein reported is a case of primary small cell carcinoma of the prostate with immunohistochemical examination of KIT and platelet-derived growth factor-α. The present case is unique in that the small cell carcinoma did not express neuroendocrine antigens. A 68-year-old man was found to have high serum prostate-specific antigen, and biopsy showed malignant small tumor cells fulfilling the small cell carcinoma criteria of the World Health Organization. Immunohistochemically, tumor cells were positive for pan-cytokeratin, KIT, platelet-derived growth factor-α, p53, Ki-67 labeling = 65%, prostate-specific antigen and alpha-methylacyl-CoA racemase. Tumor cells were negative for vimentin, CD56, synaptophysin, chromogranin and neuron-specific enolase. Imaging modalities showed multiple metastases, and the patient was treated by chemotherapy. The present report is the fifth with immunohistochemistry of prostatic small cell carcinoma.

Angiosarcoma of the oral cavity is extremely rare. A 54-year-old woman consulted to our hospital because of mass of the left cheek next to the mandible. MRI showed a 1 cm tumor. Enucleation of the tumor was performed. Grossly, the tumor was not encapsulated and had a central cavity. Histologically, the tumor consisted of spindle and polygonal cells with hyperchromatic nuclei with nucleoli. Intracytoplasmic vacuoles and mitotic figure were scattered. Vasoformative channels were present in some areas. Lymphoid follicles were scattered in the tumor. The tumor was invasive into the surrounding tissue, and lymphovascular permeation was noted. The surgical margins were positive. Immunohistochemically, the tumor cells were positive for factor VIII-related antigen, CD31, CD34, vimentin, p53 protein, but negative for pancytokeratins, cytokeratin (CK) 7, CK 18, CK19, EMA, S100 protein, α-smooth muscle antigen, desmin, p63, synaptophysin, chromogranin, neuron-specific enolase, CD56, CD10, CD20, CD30, CD45RO, melanosome, myoglobin, KIT, and PDGFRA. The Ki-67 labeling was 46%. The lymphoid tissue in the tumor was positive for CD20, CD45, CD45RO, and CD10. A pathological diagnosis of angiosarcoma was made. No metastatic lesions are found now. Radical operation is planned now.

The author reports a very rare case of spindle cell carcinoma of the common bile duct with an emphasis on immunohistochemical features. A 65-year-old man was admitted to our hospital because of jaundice. Imaging modalities revealed a tumor of the common bile duct, and bile cytology demonstrated malignant cells. A pancreatico-duodenectomy was performed. Grossly, an elevated tumor (15 × 10 × 3 mm) was present in the middle portion of the common bile duct. Microscopically, the tumor consisted of well-differentiated adenocarcinoma (20% in area) and spindle cell carcinoma (80% in area). There were gradual transitions between the two. The tumor cells invaded into the serosa. Immunohistochemically, the spindle cell carcinoma element was positive for four types of pancytokeratins, cytokeratin 7 (CK7), CK8, CK18, CK19, CK20, epithelial membrane antigen, vimentin, p53 protein, Ki-67 (labeling = 52%), and CEA. It was negative for high-molecular-weight CK, CK5/6, CK14, p63, neuron-specific enolase chromogranin, synaptophysin, CD56, CA19-9, CD34, desmin, S100 protein, myoglobin, α-smooth muscle antigen, CD34, CD68 and KIT. The adenocarcinoma element showed similar immunoreactivity except for negative vimentin, and positive CA19-9. The present case is the first report of spindle cell carcinoma of the common bile duct demonstrating an extensive immunohistochemistry. The spindle cell carcinoma in the present case may be derived from sarcomatous transformation of the adenocarcinoma element. CK20 newly emerges in the development of spindle cell carcinoma of the common bile duct.

Vulvar sarcomatoid squamous cell carcinoma has been rarely reported. Case report and immunohistochemistry. The author herein reports a peculiar vulvar tumor. An 87-year-old woman with hypertension presented with a vulvar tumor, and admitted to our hospital. Gross examination showed an elevated tumor measuring 3 × 4 × 5 cm in the vulva near the urethra. An excisional biopsy was taken, and it showed proliferation and invasion of malignant spindle cells (70% in area) and malignant polygonal cells (30% in area). There were gradual transitions between vulvar squamous epithelium and these malignant tumor cells. Immunohistochemically, the malignant sarcomatoid cells (spindle and polygonal cells) were positive for cytokeratins, epithelial membrane antigen, vimentin, α-smooth muscle actin, S100 protein, and p53 protein. They were negative for melanosome, CD34, CD68, myoglobin, and CD45. Ki-67 labeling was 63%. A pathological diagnosis of sarcomatoid squamous cell carcinoma expressing smooth muscle antigen and S100 protein was made. The patient developed lung metastasis 2 months later, and suddenly died of unknown cause. A rare case of vulvar sarcomatoid squamous cell carcinoma expressing S100 protein and α-smooth muscle actin is reported.

The author herein reports a very rare case of large cell neuroendocrine carcinoma (LCNEC) with sarcomatous changes of the endometrium. A 40-year-old woman was admitted to our hospital because of abnormal uterine bleeding. Gynecologic examination and imaging modalities revealed a polypoid tumor of the uterine corpus. Uterine curettage biopsy revealed a sarcomatous undifferentiated carcinoma. Simple hysterectomy, salpingo-oophorectomy, extensive lymph node dissection, and omentectomy were performed. The patient was diagnosed as having FIGO stage Ib (T1N0M0) carcinoma, and adjuvant chemotherapy was performed. The patient is now alive 16 months after the operation. Pathologically, a polypoid tumor measuring 3×2×2 cm3 was found in the uterine corpus. Histologically, the tumor consisted of relatively large-sized carcinoma cells without differentiation. The tumor cells have abundant cytoplasm and prominent nucleoli. It was composed of a spindle cell component (40%) and an epithelioid component (60%). A gradual transition between the two was recognized. Immunohistochemically, both elements showed the same immunophenotypes. The carcinoma cells were positive for cytokeratin, vimentin, CA125, CD34, estrogen receptor, progesterone receptor, p53 protein, Ki-67 antigen (80%), synaptophysin, CD56, KIT, and PDGFRA. They were negative for epithelial membrane antigen, CEA, desmin, S100 protein, melanosome, α-smooth muscle actin, chromogranin, and neuron-specific enolase. A molecular genetic analysis revealed no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. The final diagnosis was LCNEC with sarcomatous changes.

Although several studies have reported the incidence of KIT and PDGFRA gene mutations in cutaneous melanomas of Caucasians, only one report is available for Mongoloids, including Japanese. In Japan, melanoma is an uncommon neoplasm compared with countries with Caucasian populations.In this study, protein expression and gene mutations of these two genes were investigated by immunohistochemistry and PCR-direct sequencing in 12 primary cutaneous invasive melanomas of Japanese patients. Acral melanoma was detected in 2 cases, chronically sun-damaged skin melanoma in 3 cases, and non-chronically sun-damaged skin melanoma in 7 cases. Genetic analysis was performed in exons 9, 11, 13, and 17 of the KIT gene and in exons 12 and 18 of the PDGFRA gene.Point mutations of the KIT gene were recognized in only one (8%) case, codon 559 of exon 11 (GTT → GCT). This is a melanoma of the sole (acral melanoma). No mutations of the PDGFRA gene were recognized. At the protein level, 11 case (92%) showed membranous expression of KIT; the expression did not correlate with melanoma depth. KIT expression was stronger in the peripheral in situ or minimal invasive areas than the central invasive areas. Membranous PDGFRA expression was found in all cases (100%).In this study, only 8% of melanomas had the KIT mutation in this Japanese population. The finding of a mutation in one of two acral melanomas suggests that KIT inhibitors, for example imatinib, which are already used in clinics for treatment of GIST, can also be used for melanoma.

The author reports a very rare case of cutaneous metastasis of sarcomatoid carcinoma of the lung. The skin metastasis was an initial presentation. A 67-year-old man consulted our hospital because of left chest skin mass. An excisional biopsy was performed, and it showed proliferation of malignant sarcomatoid spindle and polygonal cells in the deep dermis and subcutis remote from the epidermis and appendages. Immunohistochemically, the tumor cells were positive for pancytokeratins, cytokeratin (CK) 7, CK 18, vimentin, p53, Ki-67 (95%) and PDGFRA. They were negative for high molecular weight CK, CK 5/6, CK 14, CK 19, CK 20, epithelial membrane antigen, TTF-1, CEA, desmin, S100 protein, α-smooth muscle actin, p63, CD34, surfactant apoprotein A, chromogranin, synaptophysin, neuron-specific enolase, CD68, CD56, D2-40, calretinin and KIT. A pathological diagnosis of metastatic sarcomatoid carcinoma probably originating from the lung was made. Then, the patient was admitted to our hospital, and imaging modalities including compured tomography (CT) and magnetic resonance imaging (MRI) revealed a tumor in the left lung. No other tumors were detected in the imaging techniques. Lung biopsy was planned, but the patient suddenly died; the cause of death was unclear. Autopsy was not performed. The present report suggests that sarcomatoid carcinoma of the lung should be considered in cutaneous metastatic lesions. Terada T. Sarcomatoid carcinoma of the lung presenting as a cutaneous metastasis.

Neuroendocrine carcinoma of the esophagus including small-cell carcinoma and large-cell carcinoma is a very rare entity. The author herein reports a neuroendocrine carcinoma of the esophagus with an emphasis on KIT and PDGFRA. An 81-year-old man presented as dysphagia. An endoscopic examination revealed an ulcerated large tumor in the middle esophagus. A biopsy of the esophageal tumor identified an undifferentiated carcinoma consisting of malignant cells with hyperchromatic nuclei without differentiations. An immunohistochemical study revealed that the tumor cells were positive for cytokeratins, neuron-specific enolase, synaptophysin, p53 protein, KIT, and platelet-derived growth factor receptor-α (PDGFRA). The Ki-67 labeling was 100%. A pathologic diagnosis of neuroendocrine carcinoma with expression of KIT and PDGFRA was made. A genetic analysis using PCR direct sequencing method identified no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. The patient underwent radiation and cisplatin-based chemotherapy. However, he developed systemic metastases and died of respiratory failure 8 months after the first manifestation. The present case is the first one of esophageal neuroendocrine carcinoma with an examination of protein expressions and gene mutations of KIT and PDGFRA.

Reports of cutaneous myopericytoma (MPC) are very rare. The author herein reports a case of minute MPC of the neck. A 56-year-old woman noticed a painful small tumor in the neck, and consulted to our hospital. Dermatologists's diagnosis is a hyperplastic lymph node. Excision of the tumor was performed. Grossly, the tumor was a sold white tumor measuring 3 × 3 × 3 mm. Microscopically, it consisted of many vascular channels and perivascular cell proliferation encased by a fibrous capsule. The vascular proliferation showed a hemangiopericytoma (HPC)-like pattern such as staghorn-like vessels. Fibrosis was not present. The HPC-like cells had vesicular nuclei and polygonal cytoplasm. No atypia is recognized. The HPC-like cells focally showed vague nodular proliferation around the vessels. Immunohistocheically, the tumor cells were negative for cytokeratin, and positive for vimentin. The vasculatures were positive for factor VIII-related antigen, CD34, and CD31. The HPC-like tumor cells were positive for α-smooth muscle actin and h-caldesmon, but negative for desmin, S100 protein, melanosome, bcl-2, CD99, and KIT. The Ki-67 labeling was 8% and p53 was negative. The pathologic diagnosis was MPC of the neck skin. The patient is now alive without recurrence 4 years after the excision. A review of the literature revealed 73 cases of MPC from 6 papers. MPC is male predominance, and the patients ages ranges from 13 to 87 years with the median of 47 years. The most common location was lower extremities followed in order by upper extremities, head and neck, and trunk. One MPC occurred within the vasculature, and 3 cases of MPC developed in the scar or trauma lesions. The prognosis after excision is good, but a very minority showed local recurrence. A differential diagnosis was also made.

A 74-year-old woman was admitted in an hospital because of abnormal lung shadow in chest X–P. Imaging modalities including CT, MRI, and PET demonstrated a small (12 mm in diameter) mass in the periphery of the right upper lobe. Although biopsy and cytology were negative, wedge resection was performed. Grossly, the lesion was a round white tumor measuring 10 × 10 × 9 mm located beneath the pleura. Microscopically, the tumor consisted of proliferation of atypical spindle cells with hyperchromatic nuclei. The tumor cells were continuous with bronchial smooth muscle. Mitotic figures were recognized in 20 per 10 high power fields. There were foci of necrosis and deposition of dusts and hemosiderin. Residual bronchi were present within the tumor. Immunohistochemically, the tumor cells were positive for vimentin, α-smooth muscle actin, caldesmon, and Ki-67 (labeling = 50%), but negative for cytokeratins (AE1/3, CAM5.2, KL-1, and polyclonal wide), cytokeratin 5/6, cytokeratin 7, cytokeratin 20, epithelial membrane antigen, melanosome, TTF-1, desmin, CD34, calreninin, D2-40 (podoplanin), S100 protein, p53 protein, myoglobin, KIT, and platelet-derived growth factor receptor-α (PDGFRA). The author diagnosed the lesion as leiomyosarcoma. After the pathological diagnosis, CT, MRI and PET of the whole body were performed, but did not reveal any tumors including the uterus. The patient was followed up, and three years later a recurrent lesion (20 mm in diameter) was identified in the right upper lobe near the previous tumor. Biopsy showed leiomyosarcoma with histology and immunohistochemical findings similar to the previous tumor. Further operation was impossible because of her medical conditions. She was treated by chemotherapy and followed up. She was now alive with the small pulmonary tumor, which shows no rapid growth.

Because incidence and immunohistochemical features of pulmonary pleomorphic carcinoma (PC) are unclear, the author retrospectively surveyed and re-examined the archival 718 lung malignancy samples in our laboratory. As the results, one case of pulmonary PC was found; thus the incidence of pulmonary PC was 0.14% of all lung malignancies. A 67-year-old woman with asthma was found to have a rapidly growing tumor in the peripheral lower lobe of right lung at a private clinic, and was referred to our hospital. She was a non-smoker. Imaging modalities showed a cystic tumor, and clinical diagnosis was bronchogenic cyst. Right lower lobectomy was performed. The patient is now alive without tumors six years after the operation. Grossly, the tumor was well-defined white tumor with necrosis. The tumor measured 5 × 4 × 5 cm. Histologically, the tumor was pulmonary PC consisting of malignant spindle and giant cells with focal tubular formations. Necrotic foci and numerous mitotic figures were present. Immunohistochemically, tumor cells were positive for pancytokeratin, high molecular weight cytokeratin (CK), CK5/6, CK7, CK14, CK18, CK19, epithelial membrane antigen, vimentin, p53 protein, surfactant apoprotein A, neuron-specific enolase, lysozyme, Ki-67 (60%), and CD68. Tumor cells were negative for CK20, thyroid transcriptional factor-1, CEA, S100 protein, desmin, α-smooth muscle actin, melanosome, CD34, p63, chromogranin, synaptophysin, CD56, KIT, and platelet-derived growth factor-α. It appeared that the present pulmonary PC is associated with adenocarcinoma or derived from sarcomatous transformation of adenocarcinoma.

Primary small cell carcinoma of the endometrium is very rare, and there have been no reports on KIT and PDGFRA in endometrial small cell carcinoma.An 87-year-old woman was admitted to our hospital because of genital bleeding. Endometrial cytology and biopsy revealed small cell carcinoma. Scrutiny of the body showed stage III endometrial carcinoma with metastases. An immunohistochemical study of the biopsy specimens revealed positive reactions for synaptophysin, CD56, KIT, and PDGFRA, and negative reactions for cytokeratins, neuron-specific enolase, and chromogranin. A molecular genetic analysis using PCR-direct sequencing identified no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. The patient received chemotherapy and radiation, but showed a downhill course, and died of carcinomatosis 6 months after the initial presentation.The present case is the first reported case of primary small cell carcinoma of the endometrium with an examination of KIT and PDGFRA expressions and KIT and PDFGRA gene mutations.

The author reports a rare case of sarcomatoid carcinoma with an emphasis on immunohistochemical features. A 79-year-old man was admitted to our hospital because of hematuria. An endoscopy revealed a large polypoid tumor in the bladder, and urine cytology demonstrated malignant cells. A cystectomy was performed. The patient is now alive without metastasis 4 months after the operation. Grossly, a large polypoid tumor (5 x 6 x 5 cm) was present in the bladder. Microscopically, the tumor consisted of high-grade transitional cell carcinoma element (10% in area) and sarcomatoid element (90% in area). There was a gradual transition between the two. The tumor cells were invaded into peribladder tissue (pT3b). Immunohistochemically, the sarcomatoid element was positive for four types of pancytokeratins, high-molecular weight cytokeratin (CK), CK5/6, CK7, CK18, CK19, epithelial membrane antigen (EMA), vimentin, p53 protein, p63, Ki-67 (labeling = 92%), neuron-specific enolase (NSE), and platelet-derived growth factor receptor-alpha (PDGFRA). It was negative for CK14, CK20, melanosome, carcinoembryonic antigen (CEA), desmin, S100 protein, myoglobin, alpha-smooth muscle antigen (ASMA), CD34, chromogranin, synaptophysin, CD56, CD68, and KIT. The transitional cell carcinoma element showed similar immunoreactivity except for negative CK5/6, positive CK20, and negative vimentin. A molecular genetic analysis of KIT gene (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) gene with the use of PCR-direct sequencing showed no mutations. The present case is the first report of sarcomatoid carcinoma of the urinary bladder demonstrating extensive immunohistochemistry and mutational status of KIT and PDGFRA genes. The sarcomatoid carcinoma in the present case may be derived from sarcomatous differentiation of high-grade transitional cell carcinoma.

Only one case of carcinosarcoma in the pouch of douglas has been reported in the English literature. The author herein reports a case of carcinosarcoma of the pouch of douglas. A rapidly growing tumor (10 cm in diameter) was found in the pelvic cavity of a 51-year-old woman, and an operation was performed for the clinical diagnosis of left ovarian malignancy. However, it was found that the tumor was located in the pouch of douglas, free of ovarian involvement. Because the tumor was impossible to resect totally, an incisional biopsy was performed. Histologically, the tumor showed a mixture of squamous cell carcinoma, atypical epithelial cells occasionally forming tubules, myxomatous spindle cell sarcoma, and chondrosarcoma. The tumor showed abundnat vessels, hemorrhage and necrosis. Immunohistochemically, the squamous cell carcinoma and atypical epithelium components were positive for cytokeratins, CEA, CA125, and p53 protein. The spindle cell sarcoma and chondrosarcoma components were positive for vimentin and p53 protein. The overall Ki-67 labeling was 30%. The author diagnosed the present case as carcinosarcoma of heterologous type. The present case shows that carcinosarcoma can occur in the pouch of douglas. It may arise from misplaced Mullerian duct remnants in the pouch of douglas.

The author reports a rare autopsy case of primary small cell carcinoma of the urinary bladder with an emphasis on KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes. An 81-year-old man was admitted to Shizuoka City Shimizu Hospital because of dysuria. Cytology of the urine showed small carcinoma cells. Transurethral bladder tumorectomy indicated small cell carcinoma, and the patient was treated by radiation and chemotherapy. The patient died, however, of systemic metastasis 2 months after the first presentation. An autopsy showed a bladder small cell carcinoma and it systemic metastasis. Immunohistochemistry of the tumorectomy and autopsy specimens was positive for cytokeratins, neuron-specific enolase, synaptophysin, CD56, KIT and PDGFRA, and negative for chromogranin and thyroid transcriptional factor-1. Polymerase chain reaction-direct sequencing showed no mutations of KIT (exons 9, 11, 13 and 17) or PDGFRA (exons 12 and 18) genes in the tumorectomy specimens and was non-contributory due to DNA damage in autopsy specimens. The present case is the first case of primary small cell carcinoma of the urinary bladder involving examination of KIT and PDGFRA expression and KIT and PDGFRA gene mutations.

Esophageal carcinoma with multiple differentiation is very rare. The author herein reports a case of esophageal carcinoma with triplicate differentiation (squamous cell carcinoma, small cell carcinoma, and adenocarcinoma). A 78-year-old man was admitted to our hospital because of dysphagia. An endoscopic examination revealed a polypoid tumor (3 x 4 x 3 cm) in the distal esophagus, and biopsy was obtained. The biopsy showed a tumor composed of moderately differentiated squamous cell carcinoma, small cell carcinoma, and adenocarcinoma. The proportions of them were 40% in squamous cell carcinoma component, 50% in small cell carcinoma component, and 10% in adenocarcinoma. There were gradual merges among them. Immunohistochemically, squamous cell carcinoma component was positive for cytokeratins and p53 protein. The Ki-67 labeling was 43%. The small cell carcinoma component was positive for cytokeratin, p53 protein, CD56, and KIT. The Ki-67 labeling was 95%. The adenocarcinoma component was positive for mucins, cytokeratin, p53 protein and CEA. The KI-67 labeling was 52%. The author speculates that this carcinoma arise from totipotent stem cell of the esophagus. The patient was treated by chemoradiation therapy, but died of systemic metastasis 13 months after the initial manifestation.

The author reviewed 931 consecutive esophageal biopsies in the last 15 year in out pathology laboratory of our hospital in search for benign esophageal tumors. As the results, 41 cases (4.4%) of squamous papilloma, 4 cases (0.4%) of granular cell tumor, 3 cases (0.3%) of leiomyoima, and 1 case (0.1%) tubular adenoma were identified. The 41 cases of squamous papillma were located in the cervical esophagus in 6 cases, in the proximal esophagus in 12 cases, in the middle esophagus in 11 cases, and in the distal esophagus in 12 cases. The squamous papilloma was immunohistochemically positive for various cytokeratins. It was endoscopically recognized as small polypoid tumor. The age ranged from 35 years to 81 years with a mean of 51 years. Male to female ratio was 25:16. The 4 cases of granular cell tumor were located in the proximal esophagus in 3 cases, and in the middle esophagus in 1 case. The granular cell tumor was immunohistochemically positive for vimentin, S100 protein, and neuron-specific enolase. It was endoscopically recognized by elevated small lesions. The ages of were 36, 45, 67 and 78 years, and male to female ratio was 1:3. The 1 case of tubular adenoma was located in the distal esophagus. Histologically, it was associated with heterotopic gastric mcusa, and immunohistochemically faintly positive for p53 protein and Ki-67 antigen. It was endoscopically a slightly elevated lesion. The patient was 46 year-old man. The 3 cases of leiomyoma were located in the cervical esophagus in 1 case and in the proximal esophagus in 2 cases. It was immunohistochemically positive for vimentin, α-smooth muscle actin, and desmin. It was endoscopically recognized as a submucosal tumor. The ages were 34, 45, and 85 years. Male to female ratio was 1:2.

The author reports a very rare case of a gastrointestinal stromal tumor in the uterus. A 74-year-old woman was admitted to our hospital because of pelvic pain. Imaging modalities showed a large tumor of the posterior aspect of the uterus, and enucleation was performed. The tumor was attached to the posterior uterus, similar to subserosal leiomyoma. No attachment to the gastrointestinal organs was recognized. The tumor was soft, tan, and measured 13 x 15 x 12 cm. The tumor consisted of cellular spindle cells with focal necrotic areas. Mitotic figures were noted in 3 of 50 high-power fields. The tumor cells were positive for KIT, CD34, platelet-derived growth factor receptor alpha, and vimentin, but negative for alpha-smooth muscle actin, S100 protein, p53 protein, HMB45, and desmin. Ki-67 labeling was 3%. Five normal uteruses used as controls showed KIT-positive Cajal-like mesenchymal cell scattering in the myometrium. Genetic analyses of the c-kit gene (exons 9, 11, 13, and 17) and platelet-derived growth factor receptor alpha gene (exons 12 and 18) revealed a point mutation at codon 559 (GTT--GAT) of exon 11 of the c-kit gene. Other exons showed no abnormalities. This case shows that gastrointestinal stromal tumor may occur in the uterus.

A case of pseudolymphoma (reactive lymphoid hyperplasia) of the liver in a 66 year old female is presented. A tumor-like lesion was incidentally discovered in the liver during clinical follow up of diabetes mellitus. The hepatic lesion was resected because malignant lymphoma was suspected after a needle biopsy. Grossly, the lesion was well-defined and measured 1.0 x 1.5 x 1.0 cm. Microscopically, the lesion consisted of hyperplastic lymphoid follicles with distinctive germinal centers and interfollicular areas consisting of mature lymphocytes and plasma cells. An immunohistological study revealed that the lymphoid cells of the lesion were polyclonal in immunophenotypes. These histological and immunohistochemical findings strongly suggested a pseudolymphoma and not hepatic inflammatory pseudotumor. This case was diagnosed as pseudolymphoma of liver. Only a few cases of hepatic pseudolymphoma have so far been reported in the English literature.

The incidence and morphology of cavernous vasculatures in livers with hepatocellular carcinoma were examined. These vasculatures were grossly or microscopically found in 64% of 102 autopsied livers with hepatocellular carcinoma, though the incidence of grossly visible vasculatures was only 7%. These vasculatures were preferentially found within the portal tracts in the vicinity of portal veins obstructed by tumor emboli, especially in the cases with marked tumor emboli of the portal venous system. A majority of these vasculatures showed histochemical and immunohistochemical characteristics of blood vessels. Our findings suggest that these vasculatures frequently develop as collaterals of portal veins obstructed by the tumor emboli in hepatocellular carcinoma.

Aims/Background: This study was conducted to evaluate the expression of pancreatic digestive enzymes in hilar bile ducts and hepatocytes during human fetal liver organogenesis. Methods: We investigated the expression of pancreatic alpha-amylase protein and messenger RNA (mRNA) in hilar primitive bile ducts and hepatocytes by immunohistochemistry and in situ hybridization techniques, using 11 human fetal livers of various gestational ages. The specificity of the immunohistochemistry and in situ hybridization procedures was confirmed by Western blot analysis and in situ hybridization using sense probes, respectively. Results: Immunoreactivity of pancreatic alpha-amylase protein and expression of pancreatic alpha-amylase mRNA were present not only in the primitive ductal cells of the hilar region including the ductal plate, remodelling bile ducts and remodeled bile ducts but also in primitive hepatocytes of the hilar region, though the immunoreactivity and mRNA signals in the primitive hepatocytes disappeared in the third trimester. There was perfect correlation between immunohistochemistry and in situ hybridization. Conclusions: These results suggest that primitive biliary cells and hepatocytes of the hilar region in the human fetus do express pancreatic alpha-amylase protein and mRNA, and that the primitive biliary epithelial cells and hepatocytes in the hilar region share a common cell lineage with exocrine pancreatic cells.

Reactive follicular hyperplasia of the intraparotid lymph nodes (IPLs) forming a parotid tumor has rarely been reported, and the pathogenesis of Warthin's tumor has not been determined. A case of hyperplastic IPLs with incipient Warthin's tumors presenting as a parotid tumor is presented. A 68-year-old Japanese patient presented with a tumor of the right parotid gland, and the tumor was resected. Pathologic examination showed seven hyperplastic IPLs (3–15 mm in diameter) with follicular hyperplasia with a capsule, marginal sinuses, and high endothelial venules. Very small foci of Warthin's tumor were recognized in two of the IPLs. Non-tumorous ductules were scattered in four IPLs. Immunohistochemical studies showed that the oncocytes of the small Warthin's tumor and the ductular elements were positive for cytokeratin, but negative for carcinoembryonic antigen, vimentin, α -smooth muscle antigen, and S100 protein. The ki-67 labeling was 3%. CD20-positive B lymphocytes were located in the germinal center and peripheral B zone, and CD3-positive T lymphocytes in the interfollicular T zone. The present case suggests that reactive hyperplastic IPLs may form a parotid tumor, and that Warthin's tumor may develop in hyperplastic IPLs at the inception of its tumorigenesis.

The authors report a rare case of primary mucinous carcinoma of the skin initially diagnosed as a metastatic adenocarcinoma. The tumor occurred in the right axilla in a 75-year-old man. Initial pathological diagnosis was metastatic adenocarcinoma. However, no primary focus was found in the body. The revised diagnosis by the authors was primary cutaneous mucinous carcinoma. The tumor (1.5 cm) was characterized by proliferation of atypical epithelial cells arranged in cell nests with many pseudolumens resembling adenoid cystic carcinoma. It was also characterized by much mucinous stroma or pool around tumor cells. No apparent eccrine or apocrine differentiation was noted histologically and immunohistochemically. The present case suggests that primary cutaneous mucinous carcinoma may be misdiagnosed as metastatic adenocarcinoma, and that it may resemble adenoid cystic carcinoma.

Hepatobiliary cystadenoma and cystadenocarcinoma of the gall bladder have rarely been reported. An 88-year-old Japanese man was admitted to our clinic because of hypochondralgia and jaundice. Imaging techniques revealed hemobilia and a multilocular cystic tumor in the fundus of the gall bladder, and cholecystectomy was performed. Grossly, the tumor (3.5 x 3 x 3 cm) was multicystic, containing seromucous fluid. The tumor was located in the fibromuscular layer and subserosa of the gall bladder fundus, and protruded into the serosal surface, not into gall bladder lumen. The mucosa appeared free of tumor involvement, and no gall stones were recognized. Microscopically, the tumor was located in the fibromuscular layer, subserosa and tiny focus of the mucosal surface. The tumor consisted of mucin-rich benign columnar cells, dysplastic mucous cells, malignant papillotubular cells and invasive carcinoma cells. Malignant and atypical tumor cells were located in the center of the tumor and in the tiny area of the mucosal surface, while benign tumor cells were located in the peripheral portions of the tumor and in the serosal side. Neither ovarian stroma-like mesenchymal stroma nor an oncocytic change in tumor cells was recognized. Non-tumorous gall bladder showed chronic cholecystitis. Immunohistochemically, benign and carcinoma cells were positive for cytokeratins, epithelial membrane antigen, CA19-9, MUC1, MUC5AC and MUC6, and carcinoma cells were also positive for carcinoembryonic antigen and p53 protein. The present case indicates that hepatobiliary cystadenocarcinoma without mesenchymal stroma may occur in the gall bladder of old men, and suggests that hepatobiliary cystadenoma without mesenchymal stroma may transform into hepatobiliary cystadenocarcinoma in the gall bladder.

Background/Aims : The human proto-oncogene c-erbB-2 (also called HER-2/neu) is located on chromosome 17q21-22. There have been no studies on gene amplification or mRNA expression of c-erbB-2 in human intrahepatic cholangiocarcinoma (CC) hitherto. Methods : We investigated c-erbB-2 gene amplification by fluorescence in situ hybridization (FISH), c-erbB2 mRNA expression by ISH, and c-erbB-2 protein expression by immunohistochemistry in 22 archival cases of CC. Results : FISH revealed that c-erbB-2 gene signals were increased in CC. ISH showed that c-erbB-2 mRNA signals were located in the nuclei and cytoplasms of cancer cells and were increased in cancer cells compared with non-cancerous bile ducts where no signals were present. Immunohistochemistry showed that the c-erbB-2 protein was expressed in the cell membrane of cancer cells, and was increased compared with non-cancerous bile ducts where no expression was found. There was a positive significant correlation between c-erbB-2 mRNA and protein expression. Clinicopathologically, there were no correlations between the c-erbB-2 expression and various pathological features. Conclusions : These data suggest that c-erbB-2 gene amplification does occur in CC, and that there is an overexpressed c-erbB-2 protein through the enhanced mRNA expression. The c-erbB-2 gene amplification may be related to the oncogenesis or tumor progression of CC.

Backgrounds: Malignant melanoma (MM) of urethra is extremely rare; only 84 cases have been reported in PubMed search.Case: An 84-year-old woman presented dysuria. Physical and endoscopic examination revealed a polypoid tumor in proximal urethra, and endoscopic tumorectomy was performed. The tumor could not be seen in outer genitalia. Grossly, the tumor is brownish soft tumor measuring 15 mm × 26 mm × 23 mm. Multiple sections were made and immunohistochemical procedures were performed. Microscopically, malignant epithelioid cells with brown pigment were seen to proliferate and invade. The size of tumor was circa 13 mm × 21 mm × 18 mm. The depth of invasion was 10 mm (pT4), but it was not clear whether the marginal tissue status is positive or negative. Lymphovascular permeation seen, yet no obvious vascular invasion was noted. The brown pigment was found to be melanin by Masson-Fontana stain. Immunohistochemical study showed tumor cells were positive for vimentin, S100 protein, HMB45, Melan A, p53, and Ki67 (labeling = 85%), KIT and PDGFRA, while they were negative for cytokeratins. Genetic analysis of paraffin-embedded tumor tissue identified no mutations in hot spots of KIT and PDGFRA genes. No apparent metastatic lesions were seen after the diagnosis. The outcome of the patient is unknown because the patient was referred to a large hospital specializing in cancer treatment.Conclusions: The author presented a very rare case of MM of the proximal urethra. The MM showed typical histochemical and immunohistochemical features. No mutations of KIT and PDGFRA were seen.