Small cell carcinoma of the oral cavity (cheek mucosa): a case report with an immunohistochemical and molecular genetic analysis

Small cell carcinoma (SCC) of the oral cavity is extremely rare; only one case has been reported in the English Literature. The author herein reports the second case of SCC of the oral cavity. A 59-year-old man presented with oral tumor (5 cm) in the right cheek mucosa. A biopsy was taken. The HE histology was typical SCC consisting of small epithelial cells with hyperchromatic nuclei, molded nuclei, scant nucleocytoplasmic ratio, and negative nucleoli. Immunohistochemically, the tumor cells are positive for pancytokeratin (PCK) WSS, PCK MNF-116, cytokeratin (CK) 34BE12, CK5/6, CK14, vimentin, KIT (CD117), CD56, synaptophysin, p53 protein, and Ki67 antigen (Ki-67 labeling = 70%). The tumor cells are negative for PCK AE1/3, PSK CAM5.2, CK7, CK8, CK18, CK19, CK20, EMA, NSE, chromogranin, platelet-derived growth factor-α (PDGFRA), CD45, CD45RO, CD3, CD20, CD30, CD79a, and bcl-2. A retrospective genetic analysis using PCR-direct sequencing method in paraffin sections identified no mutations of KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. Various imaging modalities including CT and MRI and upper and lower gastrointestinal endoscopy did not identified no tumors other than the oral tumor. Thus, the oral tumor was thought primary. The oral tumor rapidly enlarged, and distant metastases to cervical lymph nodes, ribs and iliac bones emerged. The patient is now treated by cisplatin-based chemotherapy 16 months after the first manifestation.     

Pigmented adenoid cystic carcinoma of the ear skin arising from the epidermis: a case report with immunohistochemical studies

Adenoid cystic carcinoma (ACC) in the skin is very rare; only about 60 cases have been reported. Herein presented is a case of pigmented ACC arising from epidermis of the ear skin. An 85-year-old man presented black tumor of the right ear. Dermatologists' diagnosis was basal cell carcinoma (BCC). Large biopsy was obtained. The biopsy showed proliferation of atypical basaloid cells arranged in a cribriform pattern. The tumor cells were continuous with epidermis, as if it arose from the epidermis. Focal areas show melanin deposition in the tumor cells. Mucin stains showed that the tumor cells and tubular lumens contained acidic mucin. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) AE1/3, CK34BE12, CK5/6, CK7, CK14, p63, alpha-smooth muscle actin (ASMA), S100 protein, p53, Ki-67 (labeling 85%), KIT, PDGFRA and CD56. The tumor cells were negative for CK CAM5.2, CK8, CK18, CK19, CK20, EMA, desmin, CEA, HMB45, CD10, CD34, neuron-specific enolase, chromogranin, synaptophysin, CDX2, MUC1, MUC2, MUC5AC and MUC6. HMB-positive and S100-positive melanocytes were seen in a very few areas. Since characteristic cribriform pattern was recognized in the tumor and the tumor showed epithelial markers, myoepithelial markers (CD14, p63, ASMA, S100 protein) and KIT, the pathological diagnosis of ACC was made. No distant and lymph node metastasis is now seen. The patient will be treated by complete resection. The present cutaneous ACC was unique in that the ACC arose from the epidermis, had melanin pigment, and occurred in ear skin.     

Malignant myoepithelioma of the breast

Malignant myoepithelioma of the breast is rare. A 50-year-old Japanese woman was admitted to our hospital because of a right breast tumor (11 × 10 × 5.5 cm). Core needle biopsy revealed malignant spindle cells. A mastectomy was performed. The tumor consisted of malignant spindle, round, pleomorphic and giant cells with many mitotic figures and necrotic areas. Tumor and osteoclast-like giant cells were scattered. Much lymphovascular permeation was seen. In a few areas, particularly on the tumor periphery, there were merges between the tumor cells and myoepithelial cells of the non-tumorous ducts, as if the tumor emanated from the duct myoepithelium. The tumor was invasive into the skin and pectoral muscle. Immunohistochemically, the tumor cells were diffusely positive for vimentin, CD10, α-smooth muscle antigen, and Ki-67 (labeling = 95%). The significant areas of the tumor were positive for S100 protein, p63, p53, CD68, caldesmon, desmin and TGFβ1. A few areas were positive for pancytokeratin (AE1/3), cytokeratin (CK) 5/6, and CK 34βE12. In contrast, the tumor cells were negative for pancytokeratins (WSS, CAM5.2), CK7, CK8, CK14, CK18, CK19, CK20, EMA, CEA, bcl-2, myoglobin, CD34, CD56, CD45, HMB45, GFAP, α-1-antitrypsin, synaptophysin, estrogen receptor, progesterone receptor, HER2/neu, MUC1, MUC2, MUC5AC and MUC6. The author diagnosed the tumor as malignant myoepithelioma, as myoepithelial markers (C10, p63, S100 protein, α-smooth muscle actin, caldesmon) were positive, and also because there was a transition between the tumor cells and myoepithelium of non-tumorous ducts. The grade of the tumor was high. The patient was treated with chemoradiation and was free of disease 5 months after the operation.     

Adenoid squamous cell carcinoma of the oral cavity

Because immunohistochemical features of adenoid squamous cell carcinoma (AdSCC) of the oral cavity is unclear, the author reports herein AdSCC in the gingival with an emphasis on immunohistochemical features. A 73-year-old woman presented with a left lower gingival tumor. The tumor was mildly elevated tumor measuring 1.5 x 1.5 x 0.5 cm. Dentist's diagnosis was granulation tissue, and a biopsy was taken. The biopsy showed proliferation of carcinoma cells arranged in cords, and squamous and tubular differentiations were noted in places. The biopsy diagnosis was adenosquamous carcinoma. Tumor excision with resection of mandibular bone was performed. The resected tissue showed a mixture and squamous cell carcinoma and tubular formation. Gradual merges between the two and acantholytic features of the squamous cell carcinoma element were seen. Both components were free from mucins. Both components were positive for pancytokeratins (AE1/3, CAM5.2) +++, cytokeratin (CK) 5/6 +, CK34βE12 ++, CK7 +, CK14 +++, CEA +, CA19-9 +, CA125 +, p53 +++, p63 +++, KIT + and MUC1 ++. Both components were negative for CK8, CK18, CK19, CK20, EMA, vimentin, TTF-1, desmin, myoglobin, S100 protein, melanosome, smooth muscle actin, CD34, CDX2, CD10, chromogranin, synaptophysin, NSE, CD56, lysozyme, CD68, MDM2, PDGFRA, MUC2, MUC5AC, and MUC6. Since both components were positive for squmaous cell carcinoma markers (CD5/6, CK34βE12, and p63) and adenocarcinoma markers (CEA, CA19-9, CA125, MUC1), this case of AdSCC appears an intermediate form between adenocarcinoma and squamous cell carcinoma. The margins were negative. No metastasis was found by imaging techniques. The patient is now free from tumor and is followed up carefully.     

Small cell carcinoma of the urinary bladder

Primary small cell carcinoma of the urinary bladder is very rare; only several studies have been reported in the English literature. A 62-year-old woman was admitted to our hospital because of hematuria and dysuria. Bladder endoscopy revealed a large polypoid tumor at the bladder base. Transurethral bladder tumorectomy (TUR-BT) was performed. Many TUR-BT specimens were obtained. Histologically, the bladder tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK8, CK18, neurone-specific enolase, chromogranin, NCAM (CD56), synaptophysin, Ki-67 (labeling=100%), p53, KIT (CD117), and platelet-derived growth factor receptor-α (PDGFRA). The tumor cells were negative for CK5/6, CK 34BE12, CK7, CK14, CK19, CK20, p63, CD45, and TTF-1. A molecular genetic analysis using PCR-direct sequencing showed no mutations of KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. No metastases were found by various imaging techniques. The patient is now treated by cisplatin-based chemotherapy.     

Immunohistochemical profile of normal mesothelium and histiocytic/methothelial hyperplasia: a case report

Immunohistochemical profiles of normal mesothelium and histiocytic/mesothelial hyperplasia (HMH) are unknown. A 19-year-old man was treated by thoracoscopic resection of bullae of left lung. Histologically, there were cell proliferative foci composed of round cells without significant atypia (histiocyte, mesothelium and T-lymphocytes). The cell proliferative foci were patch-like, and no invasive features were seen. Because it is composed of histiocytes, mesothelium, and T-lymphocytes, the diagnosis was HMH. Immunohistochemically, cell components of HMH showed the following immunoreactions: calrenitin 3+, D2-40 3+, pancytokeratin AE1/3 3+, pancytokeratin CAM5.2 3+, cytokeratin (CK) 34βE12 1+, CK5/6 1+, CK7 1+, CK8 3+, CK 14 1+, CK18 2+, CK19 2+, p53 10%, Ki67 20%, CD68 3+, CD45 2+, CD45 RO 2+, vimentin 3+, Ber-EP4 -, CK20 -, EMA -, desmin -, CEA -, CA19-9 -, TTF-1 -, S100 protein -, αsmooth muscle actin -, CD34 -, CD20 -, chromogranin -, synaptophysin -, NSE -, CDX2 -, CD56 -, HER2 -, MUC1 -, MUC2 -, MUC5AC -, and MUC6 -. The normal mesothelium showed the following immunoprofile: calrenitin 3+, D2-40 3+, pancytokeratin AE1/3 3+, pancytokeratin CAM5.2 3+, CK34βE12 3+, CK5/6 2+, CK7 2+, CK8 3+, CK 14 -, CK18 3+, CK19 2+, vimentin 1+, p53 -, Ki67 1%, CD68 -, CD45 -, CD45 RO -, Ber-EP4 -, CK20 -, EMA -, desmin -, CEA -, CA19-9 -, TTF-1 -, S100 protein -, α-smooth muscle actin -, CD34 -, chromogranin -, synaptophysin -, NSE -, CDX2 -, CD56 -, HER2 -, MUC1 -, MUC2 -, MUC5AC -, and MUC6 -. These findings indicate that the immunoprolfile of mesothelium in HMH was immunohistochemically very similar to that of normal mesothelium except for CD68, p53 protein, Ki-67 labeling, CD45 and CD45 RO. These indicate that the HMH was reactive phenomenon and HMH is composed of hyperplastic mesothelium, histiocytes and T-lymphocytes. The immunoprofile of normal mesothelium provide basic knowledge of mesothelial pathology.     

Primary signet-ring cell carcinoma of the lung: a case report with an immunohistochemical study

Primary signet-ring cell adenocarcinoma (SRCA) of the lung is very rare. A 78-year-old man consulted to our hospital because of loss of appetite. Physical examination showed lymphadenopathy of the cervical lymph nodes. Chest X-ray showed a tumor of the right upper lobe. Blood laboratory test showed an increase of LDH and CRP. Tumor markers (CYFRA, SCC, CEA, ProGRP) were within normal range. Clinical diagnosis was suspected malignant lymphoma of the lung. Transbronchial lung biopsies showed SRCA (70%) mixed with poorly differentiated adenocarcinoma (30%). The SRCA cells were positive for mucins. Immunohistochemically, the SRCA cells were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK7, CK18, EMA, p53, Ki-67 (labeling=60%), CEA, CA19-9, TTF-1, and MUC1. They were negative for CK34BE12, CK5/6, CK8, CK14, CK19, CK20, vimentin, chromogranin, synaptophysin, CD45, CD20, CD3, surfactant Apoprotein-A, CDX-2, MUC2, MUC5AC and MUC6. A pathological diagnosis of SRCA of the lung was made. The patient showed downhill course, and died of carcinomatosis 3 months after the first manifestation. In conclusion, a vary rare case of primary pulmonary SRCA was reported with an immunohistochemical study.     

Monstrous epithelial cell clusters in the seminal vesicle

A 60-year-old man presented with dysuria and elevated PSA (6.95 ng/ml). Needle biopsies of the prostate revealed well differentiated adenocarcinoma of Gleason's score 6. Prostatectomy and bilateral seminal vesiculotomy were performed. The material was totally cut into 16 preparations. The prostate showed well differentiated adenocarcinoma. The left seminal vesicle showed intraluminal monstrous large epithelial cells with acidophilic cytoplasm and hyperchromatic nuclei, simulating carcinoma cells. Lipochrome pigment was present in the monstrous cells, and some monstrous cells showed large bizarre nuclei. Such monstrous cells were also present in the mucosal seminal vesicle epithelium, and gradual merge between the intraluminal and mucosal monstorous epithelium. Immunohistochemically, the monstrous epithelial cells showed the following reactions: pancytokeratin (AE1/3, CAM5.2) +, cytokeratin (CK) 5/6 +, CK34βE12 -, CK7 +, CK8 -, CK14 -, CK18 +, CK19+, CK20 -, Ki-67 0%, p53 -, P63 -, NSE -, CEA -, EMA -, CA19-9 -, ER -, PgR -, HER2 -, HepPar1 -, CD34 -, CD10 +, PSA -, AMACR -, Desmin -, ASMA -, CD68 -, S100 -, CD45 -, synaptopysin -, TTF-1 -, CDX-2 -, MUC1 -, MUC2 -, MUC5AC - MUC6 +, CD56 -, PAS -, dPAS -, and alcian blue +. The immunoprofile of normal seminal vesicle epithelium was as follows: pancytokeratin (AE1/3, CAM5.2) +++, cy-tokeratin (CK) 5/6 +++, CK34βE12 -, CK7 +++, CK8 +, CK14 -, CK18 +++, CK19, +++, CK20 -, KI-67 1%, p53 -, P63 +++, NSE -, CEA - EMA -, CA19-9 -, ER -, PgR -, HER2 +, HepPar1 -, CD34 -, CD10 +, PSA -, AMACR -, Desmin -, ASMA -, CD68 -, S100 - , CD45 -, synaptopysin -, TTF-1 -, CDX-2 -, MUC1 -, MUC2 -, MUC5AC -, MUC6 +++, CD56 -, PAS -, dPAS -, and alcian blue +. That is, the immunophenotype was very similar but much weaker in monstrous cells than in normal seminal vesicle epithelium. These findings suggest that the monstrous seminal vesicle epithelial cells are degenerative changes. The monstrous epithelial cells should not be mistaken for carcinoma.     

Primary small cell carcinoma of the maxillary sinus: a case report with immunohistochemical and molecular genetic study involving KIT and PDGFRA

Primary small cell carcinoma of the nose and paranasal sinuses is very rare; only a few reports are present in the English literature. The author herein reports a very rare case of primary small cell carcinoma of the maxillary sinus with an emphasis on immunohistochemistry and on KIT and PDGFRA. A 64-year-old man was admitted to our hospital because of left nasal obstruction. Endoscopy revealed three nasal polyps, and imaging modalities revealed an infiltrative tumor (45 x 45 mm) in the left maxillary sinus with invasion into nasal cavity. Multiple biopsies are taken from the nasal lesions. Histologically, the tumor consists of proliferation of malignant small epithelioid cells with hyperchromatic nuclei, fine chromatin, scant cytoplasm, molded nuclei, and absent nucleoli. Immunohistochemically, the malignant cells were positive for cytokeratin (CK) 18, synaptophysin, CD56, p53, Ki-67 (labeling=95%), bcl-2, KIT, and PDGFRA. However, they were negative for pancytokeratins, high molecular weight CK, CK5/6, CK7, CK 14, CK 19, CK20, vimentin, neuron-specific enolase, chromogranin, CD15, CD45, S100 protein, CEA, CA19-9, glial fibrillary acidic protein, neurofilaments, neuroblastoma, CD99, surfactant apoprotein A, melanosome, and TTF-1. The pathologic diagnosis was small cell carcinoma. A molecular genetic analysis using PCR-direct sequencing was performed using paraffin sections, and it showed no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. Imaging modalities including CT, MRI and PET did not reveal any tumors, including the lung, other than the maxillary sinus tumor. The present case is the first of small cell carcinoma of the maxillary sinus with a comprehensive immunohistochemical examination and a gene analysis of KIT and PDGFRA.     

Sarcomatoid carcinoma in the pelvic cavity

Sarcomatoid carcinoma in the pelvic cavity is very rare. A 58-year-old Japanese man was admitted to our hospital because of lower abdominal fullness. CT and MRI revealed a large mass in the left pelvic cavity. Transurethral bladder endoscopy showed tumor invasion, and large biopsies were obtained from the bladder lesion. Histologically, the tumor was composed of malignant round cells with hyperchromatic nuclei. Many intracytoplasmic vacuoles were present. No carcinomatous areas were seen. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 18, vimentin, p53 and Ki-67 (labeling 80%). The tumor cells were negative for panCK AE1/3, CD5/6, CK7, CK8, CK14, CK19, CK20, CK 34BE12, EMA, desmin, calretinin, WT-1, S100 protein, α-smooth muscle actin, CEA, CD34, CD45, CD20, factor VIII-related antigen, synaptophysin, p63, CDX2, and myoglobin. Because the CK18 was diffusely expressed, the pathological diagnosis was sarcomatoid carcinoma.     

Intraductal tubular carcinoma, intestinal type, of the pancreas

Presented herein is an unusual case of intraductal tubular carcinoma, intestinal type, of the pancreas. This tumor was characterized by intraductal adenoma with a few malignant foci, and also by entire involvement of the main pancreatic duct and no involvement of its branches. A 67-year-old man was admitted to hospital because of abdominal pain. On endoscopy and endoscopic retrograde cholangiopancreatography, irregular pancreatic duct was seen. No mucus secretion was observed on endoscopy. Because a biopsy showed tubular atypical cells, pancreato-duodenectomy was performed. Grossly, the entire main pancreatic duct had intraductal tumor, sparing its branches. No intraductal mucus was noted. Microscopically, the entire main pancreatic duct had proliferation of tubular adenomatous tumor without secretory mucins. Goblet cells were present in some areas. No pyloric type tubules were recognized. Malignant transformation was present in a few areas. No invasive features were recognized. On mucin histochemistry the tumor cell cytoplasm contained a little or no neutral and acidic mucus, and no secretory mucins were recognized. Immunohistochemically, the tumor cells were positive for cytokeratins (CK), CK 8, 9, 18, 19 and 20, epithelial membrane antigen, CDX2, carbohydrate antigen 19-9, and Ki-67 (labeling 30%), MUC2, MUC5AC and MUC6, and CD10. The tumor cells were negative for C-erbB2, MUC1, trypsin, pancreatic amylase and pancreatic lipase. The tumor cells were negative for p53 protein, but the malignant foci were positive for p53 protein and had high Ki-67 antigen (labeling 60%). The patient was free of disease 4 years after the operation. In summary, presented here is an extremely rare case of intraductal tubular carcinoma, intestinal type, showing focal malignant foci.     

Atypical polypoid adenomyoma of the uterus: an immunohistochemical study on 5 cases

Immunohistochemical studies of atypical polypoid adenomyoma (APA) of the uterus are very rare. Five cases of APA were retrieved from the surgical cases of our laboratory. The ages were 38, 41, 54, 65, and 77 years (mean ± SD, 55 ± 14.6 years). The diameters of APA were 1.2, 1.9, 2.3, 3.2, and 7.0 cm (mean ± SD, 3.12 ± 2.00 cm). Histologically, APA consisted of complex glandular element and mesenchymal fibromuscular element. No endometrial stroma was present. Mucins were found in the glands but not in the mesenchyma. The glands were consistently positive for pancytokeratin (AE1/3, CAM5.2), cytokeratin (CK) 7, CK8, CK18, CK19, vimentin, CA125, estrogen receptor, progesterone receptor, MUC1, and MUC6. The glands were consistently negative for CK14, CK20, CEA, epithelial membrane antigen, S100 protein, p53, CD10, MUC2, and MUC5AC. Some cases were positive for CK34βE12 (4/5), CK5/6 (4/5), and CA19-9 (4/5). The Ki-67 labeling ranged from 3% to 10%. The mesenchymal element was consistently positive for vimentin, α-smooth muscle actin, estrogen receptor, progesterone receptor, and CD10, while consistently negative for pancytokeratin (AE1/3, CAM5.2), CK34βE12, CK5/6, CK7, CK8, CK14, CK18, CK19, CK20, CEA, epithelial membrane antigen, S100 protein, CA125, CA19-9, p53, MUC1, MUC2, MUC5AC, and MUC6. Some cases were positive for desmin (2/5). Ki-67 labeling ranged from 1% to 8%. In conclusion, the immunoprofile of APA was reported. The findings provide basic knowledge of APA of the uterus.     

Pure sarcomatoid carcinoma of maxillary sinus and nasal cavity simulating malignant fibrous histiocytoma

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%), α?-antitrypsin, and α?-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.     

Synchronous poorly-differentiated neuroendocrine carcinoma and gastrointestinal stromal tumor of the stomach: a case report with immunohistochemical and molecular genetic analyses of KIT and PDGFRA

Although the stomach is the most common location for gastrointestinal stromal tumor (GIST) with co-primary tumors, the synchronous appearance of a poorly differentiated neuroendocrine carcinoma (NEC) and GIST in the stomach is extremely rare. To the best of our knowledge, this is the first case of gastric GIST coexisting with gastric NEC to be reported in the literature. The current study reports the case of a 71-year-old male with gastric poorly differentiated NEC and GIST discovered incidentally during surgical treatment of the NEC. Immunohistochemistry analysis showed that the NEC tumor cells were positive for CK (cytokeratin), CD57, synaptophysin, chromogranin, CD117 (KIT protein), Dog-1 (discovered on GIST-1 protein) and CD34. The synchronous GIST immunophenotype showed positivity for CD117, Dog-1 and CD34 (100%), whereas staining for CK, SMA, desmin and S100 was negative. Ki-67 labeling of proliferating cells was 90% in NEC and 1% in GIST. An accurate diagnosis was confirmed by immunohistochemical findings. Furthermore, genetic analysis using PCR direct sequencing identified no mutations in the KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. The patient developed lymph node metastases and underwent cisplatin-based chemotherapy after the operation. This is the first documented case of synchronous gastric GIST and NEC with the examination of protein expression and gene mutations in KIT and PDGFRA, which will help to further understand the etiology and pathogenesis of NEC coexisting with GIST in a gastric location.     

Myoepithelial carcinoma of pharynx expressing KIT and PDGFRA

KIT and PDGFRA expression has rarely been examined in myoepithelial carcinoma (MC) of the salivary glands. An 89-year-old Japanese woman presented with a pharyngeal mass. Gross and imaging examinations revealed an elevated mass in the middle pharynx next to the oral cavity. A biopsy revealed atypical cells, and tumorectomy was performed. The tumor was composed of atypical epithelioid cells arranged in solid nests, cords, and vague acinar patterns. Mitotic figures were recognized in 3 per 50 high power fields. Immunohistochemically, the tumor cells were positive for myoepithelial markers including cytokeratin (CK) 14, α-smooth muscle antigen, S100 protein, and p63. They were also positive for KIT, PDGFRA, pancytokeratin AE1/3, CK34βE12, CK5/6, vimentin, p53, and Ki-67 (labeling=28%). They were negative for neuron-specific enolase, CD45, CD34, CD56, chromogranin, synaptophysin, melanosome, desmin, epithelial membrane antigen, CK18, CK20, pancytokeratin (CAM5.2). A pathologic diagnosis of myoepithelial carcinoma arising from minor salivary glands was made. No metastatic lesions were found by various imaging techniques. The patient is now receiving palliative radiation therapy 2 months after the operation. The present case showed that MC can express KIT and PDGFRA.     

Large cell neuroendocrine carcinoma with sarcomatous changes of the endometrium: A case report with immunohistochemical studies and molecular genetic study of KIT and PDGFRA

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.     

Mammary and extramammary Paget's disease: an immunohistochemical study of 83 cases

AIM: Mammary Paget's disease (MPD) and extramammary Paget's disease (EMPD) are rare neoplasms. The aim of this study was, by the use of immunohistochemistry, to derive further information about the cell(s) of origin, find a diagnostically useful immunohistochemical panel and investigate candidates for possible targeted therapy. MATERIAL AND RESULTS: Sixty MPD and 23 EMPD cases were studied using antibodies to cytokeratin (CK) 34betaE12, CK8/18, CK7, CK5/6, CK20, gross cyctic disease fluid protein (GCDFP)-15, MUC1-8, epidermal growth factor receptor (EGFR) (HER1), HER3 and HER4. In all MPD cases CK7 and MUC1 were positive. CK8/18 was positive in 59/60 cases. GCDFP-15, MUC2, MUC3, MUC4, MUC7, MUC8 were positive in 29/60, 3/60, 35/47, 4/40, 3/43 and 2/45 cases, respectively. In all EMPD cases CK8/18 and CK7 were positive. MUC1, GCDFP-15, MUC5AC, MUC3, MUC8 and CK20 were positive in 22/23, 19/23, 8/19, 3/19, 1/19 and 3/23 cases, respectively. With the remaining antibodies no immunoreactivity was observed. CONCLUSION: MUC1 and low-molecular-weight CKs in conjunction with immunonegativity for high-molecular-weight CKs are the most diagnostically useful markers. MPD is caused by the epidermotropic spread of underlying tumour cells, whereas EMPD probably arises from intraepithelial cells of sweat gland origin. Targeted therapy with antibodies against EGFR (HER1), HER3 or HER4 is unlikely to prove of clinical value.     

Small oncocytic papillary renal cell carcinoma in diabetic glomerulosclerosis

Histologic and immunohistochemical features of oncocytic papillary renal cell carcinoma (RCC) have not been fully elucidated. The author herein report a case of oncocytic papillary RCC (OPRCC). A 71-year-old man with diabetes mellitus and diabetic nephropathy was found to have a small right renal tumor by CT. He had been treated with hemodialysis for chronic renal failure for 10 years. A nephrectomy was performed. Grossly, a small (1.5cm) encapsulated yellow tumor was found in the kidney. Histologically, the tumor was completely encapsulated, and consisted entirely of atypical oncocytes arranged in a diffuse papillary structure with fibrovascular cores. The oncocytes showed grade 3 atypia and pseudostratification. A few mitotic figures were seen, and psammoma bodies, foamy macrophages, and hemosiderin were scattered. Histochemically, the tumor cells were positive for colloidal iron, and negative for mucins (Alcian blue/PAS). Immunohistochemical results of the tumor were as follows: α-methylacyl-coenzyme A rasemase (AMACR) +++, vimentin +++, cytokeratin (CK) 18 +++, CD10 +++, S-100 protein +, MUC1 ++, MUC2 ++, MUC5AC ++, MUC6 ++, panCK Cam5.2 +, CK7 +, CK8 +, CK14 +, CK19 +, CK20 +, p53 +, HepPar1 +, CD68 +, platelet-derived growth factor-α (PDGFRA) +, PanCK AE1/3 -, PanCK WSS -, PanCK MNF115 -, CK 35BE12 -, CK5/6 -, EMA -, desmin -, smooth muscle antigen -, α-fetoprotein -, CEA -, estrogen receptor -, progesterone receptor -, HER2 -, p63 -, and KIT -. Ki67 labeling was 6%. These results suggest that OPRCC can express colloidal iron, low molecular weight CKs, S100 protein, MUC1, MUC2, MUC5AC, MUC6, p53, PDGFRA, and HepPar1.     

Human pancreatic mucinous cystadenoma is characterized by distinct mucin, cytokeratin and CD10 expression compared with intraductal papillary-mucinous adenoma

AIMS: To examine cytokeratin, epithelial glycoprotein (mucin) and glycoprotein CD10 expression in benign mucinous cystdenomas (MCAs) in comparison with intraductal papillary mucinous adenomas (IPMAs). METHODS AND RESULTS: Thirty MCAs of the pancreas were analysed for immunohistochemical expression of cytokeratin (CK) 7, CK20, MUC1, MUC2, MUC5AC and CD10 and were compared with 16 IPMAs. CK7 was expressed in all neoplasms. CK20 was significantly more frequent in MCAs compared with IPMAs (56.66% versus 18.75%, P = 0.027). MUC1 was more frequent in MCAs (40% versus 12.5%, P = 0.0915), whereas MUC5AC was significantly less frequent in MCAs (33.33% versus 100%). MUC2 was expressed in goblet cells of seven MCAs. In MCAs, CD10 was observed both in epithelial cells and in the ovarian-type stromal cells (24/30). Epithelial expression of CD10 was significantly lower in IPMAs (66.66% versus 6.25%, p = 0.0001). CONCLUSIONS: MCA is characterized by a significantly greater frequency of expression of CK20 and CD10 when compared with IPMA, which preferentially expresses MUC5AC.     

Micropapillary Carcinoma of the Breast with Necrosis-like Cell Death: A Case Report

A primary invasive micropapillary carcinoma of the breast in a 46-year-old woman is reported. Histologically, it was composed predominantly of papillary tumor cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells were positive for cytokeratin (CK) 7, estrogen receptor (ER), and progesterone receptor (PR), but negative for p53, CK 20, CD34, c-Erb-B2, CK5, epidermal growth factor receptor (EGFR), vimentin, and c-kit. MUC1 expression was found at the reversed apical membrane of neoplastic cell clusters. Accordingly, electron microscopy showed the lack of basement membrane and presence of microvilli at the basal surface of the tumor cells. Moreover, ultrastructural examination revealed single tumor cell death characterized by patchy condensations of chromatin throughout the nucleus. These nuclear alterations were associated with the occurrence of empty cytoplasmic vacuoles, conferring a necrosis-like phenotype to this cell death. Alternative programmed cell deaths are reviewed and their morphologic distinction is discussed.