Clear cell chondrosarcoma: an ultrastructural study.

Clear cell chondrosarcoma (CCC) is a rare neoplasm. We report here a case of CCC. A 67-year-old Japanese man presented with right arthralgia for 1 year, and histological examination of the subsequent surgical resection of the right femoral bone showed the finding of CCC. Ultrastructurally, most organelles were observed in the perinuclear area. Clear neoplastic cells contained many glycogen particles in the area of the cytoplasm lacking organelles, although glycogen particles overall seemed to be evenly distributed in the cytoplasm. Some mitochondria, Golgi complex, actin-like filaments, and rough endoplasmic reticulum were also demonstrated in the cytoplasm of clear cells. Well-developed microvilli were also seen on the surface of neoplastic cells. These structures in neoplastic cells corresponded notably to structures of normal chondrocytes. Finally, our ultrastructural findings support further evidence that clear cells in CCC may show chondrocyte differentiation and a lack of an organelles area as well as abundant glycogen particles, may contribute to the clear cell morphology in CCC.

Coexistent adenomyoepithelioma and invasive ductal carcinoma of the breast: presentation as separate tumors.

Adenomyoepitheliomas are rare breast tumors. We report an unusual case of adenomyoepithelioma associated with invasive ductal carcinoma here. Histologically, the lesion consisted of two separate tumors. One nodule corresponded to invasive ductal carcinoma consisting of tubular and trabecular arrangements of columnar or cuboidal neoplastic cells. The other tumor corresponded to adenomyoepithelioma consisting of an inner layer of neoplastic cells with basophilic cytoplasm and the outer layer of neoplastic cells with clear cytoplasm. Immunohistochemically, some myofibroblasts were observed in the stroma of both adenomyoepithelioma and invasive ductal carcinoma, but no CD34-positive stromal cells were seen in the stroma of either lesion. The stromal reaction of adenomyoepithelioma resembles that of intraductal papilloma in the previous study. To the best of our knowledge, this is the first case of coexistent adenomyoepithelioma and invasive ductal carcinoma of the breast that were discovered as separate nodules. Clinicians and pathologists should be aware of such an association because they need to distinguish such a case from malignant neoplasms arising in adenomyoepithelioma. Additionally, our preliminary report suggests that the stromal response of adenomyoepithelioma may resemble that of intraductal papilloma.

Sarcomatoid acquired cystic disease-associated renal cell carcinoma.

In this article, we report a rare case of hitherto undescribed acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) with sarcomatoid change. A 78-year-old woman had been receiving hemodialysis for fourteen years at the time when a renal tumor was encountered on the follow-up examination of the kidney. Microscopically, oncocytic cuboidal cells proliferated with tubular, cribriform or papillary growth patterns, and atypical columnar cells with abundant cytoplasm proliferated with papillary configuration. Oxalate crystal deposition was observed in the stroma and the tumor focally resembled translocation type (TFE3) RCC. Sarcomatous neoplastic cells were also seen. The cytoplasm of oncocytic and sarcomatous neoplastic cells was diffusely positive for anti-mitochondrial antibody and the ultrastructural examination detected many mitochondria in the cytoplasm of oncocytic carcinoma cells and sarcomatous neoplastic cells. The loss of chromosomes 1p, 2q11-22, 9 and 14 was observed using comparative genomic hybridization analysis. We thus report here a case of hitherto undescribed ACD-associated RCC intermingled with oncocytic cells, translocation type RCC-like area and sarcomatoid change. This is the sixth case of sarcomatoid RCC arising in end-stage kidney disease.

Elastofibroma: a histochemical, immunohistochemical, and ultrastructural study of two patients.

Elastofibroma is a rare neoplasm. In this article, we report our study of the pathogenesis of fibrosis in elastofibroma. Three tumors obtained from two patients were selected. One patient was a 57-year-old Japanese woman who had a bilateral tumor, and the other patient was a 83-year-old Japanese man. All tumors occurred in the infrascapular region. Macroscopically, the cut surface of all tumors showed a poorly defined and whitish mass with yellowish foci. Microscopically, the tumor consisted of collagen fiber bundles, abnormal elastic fibers, and spindle cells suggestive of fibroblasts. Elastica-van Gieson and Masson-trichrome stain identified abnormal elastic fibers and abundant collagen fibers, respectively, in elastofibroma. Immunohistochemically, fibroblasts were positive for CD34 but negative for alpha-smooth muscle actin and h-caldesmon. Additionally, the cytoplasm of many fibroblasts was positive for TGF-beta in all tumors. Ultrastructurally, some fibroblasts with abundant organelles in one tumor were observed in the adjacent area to amorphous elastic mass and bundles of collagen fibers. However, no myofibroblasts were ultrastructurally identified in the tumor. Finally, our study supplies further evidence that elastofibroma may show the proliferation of CD34-positive fibroblasts and contain no myofibroblasts, and that fibroblasts may produce both abnormal elastic fibers and collagen fibers through the secretion of TGF-beta.

Basal-like carcinoma of the breast: further evidence of the possibility that most metaplastic carcinomas may be actually basal-like carcinomas.

Some investigators have previously suggested that basal-like carcinoma may consist of components of invasive ductal carcinoma, not otherwise specified, metaplastic carcinoma, and medullary carcinoma. We report here two cases of breast carcinoma showing basal cell/myoepithelial differentiation. The first case was a 58-year-old Japanese woman and the second case was a 39-year-old Japanese woman. The two tumors were composed of the proliferation of epithelial cells and/or spindle-or stellate-shaped cells on the background of mucinous materials. Additionally, chondroid matrix was observed in the metastatic lesion of the first case and the primary lesion of the second case. Immunohistochemically, epithelial neoplastic cells were positive for E-cadherin and cytokeratin CAM5.2, and epithelial and spindle-or stellate-shaped cells were positive for cytokeratins 5, 14, or 17, alpha-smooth muscle actin, S-100, and p63. Our results supply further evidence that most metaplastic carcinomas may be actually be basallike carcinomas.

Possible identification of third stromal component in extraadrenal paraganglioma: myofibroblast in fibrous band and capsule.

Sustentacular and dendritic cells are known as the stromal components of extraadrenal paraganglioma. We identified a third stromal component in such a case. A 66-year-old Japanese woman complained of abdominal pain. The tumor was discovered near the right adrenal gland in the retroperitoneum. Histologically, the tumor consisting of round to oval neoplastic cells with eosinophilic cytoplasm proliferating with a "zellballen" pattern. Sustentacular cells were positive for S-100. Dendritic cells positive for HLA-DR were seen among the neoplastic nests. Additionally, many alpha-smooth muscle actin (ASMA)-positive and hcaldesmon-negative stromal cells, namely, myofibroblasts, were distributed in the capsule and fibrous band. Ultrastructurally, myofibroblasts contained many myofilaments and dense bodies in the cytoplasm. Finally, we identified the third stromal component, namely, myofibroblasts, in the extraadrenal paraganglioma. These myofibroblasts may play a role in the stromal response of host against neoplasm or the regulation of tumor growth.

Carcinoid tumor of the renal pelvis: consideration on the histogenesis.

Carcinoid tumor of the renal pelvis is an extremely rare neoplasm and only two cases have been previously reported in the English-language literature. Reported herein is a third case of carcinoid tumor arising in the renal pelvis. The tumor extending from the left renal pelvis into the left kidney was incidentally found in a 55-year-old Japanese woman. Macroscopically, the tumor was predominantly located in the dilated renal pelvis and was grayish-white on cut surface. Microscopically, neoplastic cells proliferated with a ribbon-like, trabecular, tubular and solid pattern. Furthermore, the tumor focally invaded the kidney parenchyma. No precursor lesion of neuroendocrine tumor was observed in the peripheral urothelial epithelium. Neither urothelial carcinoma nor teratoma component was observed within the tumorous mass. The cytoplasm of neoplastic cells was focally positive for Grimelius stain and focally positive for chromogranin A and synaptophysin. However, no neoplastic cells reacted with cytokeratins 7 and 20. Ultrastructurally, neoplastic cells contained dense core granules in the cytoplasm. Urologists and pathologists should recognize that carcinoid tumor may arise from the renal pelvis.

Large cell neuroendocrine carcinoma of the lung with calcification and expression of osteopontin.

A large cell neuroendocrine carcinoma (LCNEC) is a rare neoplasm. In this article, we report a case of LCNEC with stromal calcification. A 46-year-old Japanese man was found to have an abnormal shadow in the left upper lobe in a chest X-ray. As the size of the tumor increased during the follow-up, a left upper lobectomy was performed. Histological examination disclosed neuroendocrine morphology consisting of large cells, and subsequent immunohistochemistry confirmed the neuroendocrine differentiation. A diagnosis of LCNEC was established. Additionally, calcification was observed in the stroma within the tumor. Immunohistochemically, parts of neoplastic cells of LCNEC and calcified foci were positive for osteopontin. Finally, we suggest that osteopontin as well as dystrophy within the tumor may be involved in the stromal calcification of LCNEC.

Invasive micropapillary carcinoma of the colon: an immunohistochemical study.

Invasive micropapillary carcinoma has recently been reported in various anatomic sites. In this article, we report a case of micropapillary carcinoma of the sigmoid colon. A 70-year-old Japanese woman presented with bloody stool for 2 months. Detailed examination disclosed ulcerative and localized tumor in the sigmoid colon. Histological examination of the colon tumor showed a combination of conventional adenocarcinoma (60%) and micropapillary carcinoma (40%). Immunohistochemically, micropapillary carcinoma cells were positive for cytokeratin (CK) 20, carcinoembryonic antigen, and CA125, but negative for CK7, thyroid transcription factor-1, surfactant apoprotein A, estrogen receptor, and progesterone receptor. Additionally, the immunohistochemistry of epithelial membrane antigen revealed reverse polarity of neoplastic cells. Results of conventional adenocarcinoma were basically identical to those of micropapillary carcinoma. In the stroma of both conventional adenocarcinoma and micropapillary carcinoma, many myofibroblasts were present and CD34-positive stromal cells were absent. Finally, we report the fourth case of micropapillary carcinoma arising in the colon. Immunohistochemical results of CK7(-)/CK20(+) strongly suggest the colon as a primary site of micropapillary carcinoma. Additionally, micropapillary carcinoma of the colon may cause a similar stromal reaction to conventional adenocarcinoma of the colon.

Anaplastic carcinoma of the pancreas with rhabdoid features and hyaline globule-like structures.

A 59-year-old Japanese man presented with a giant submucosal tumor with ulceration during follow-up of duodenal ulcer. Pancreaticoduodenectomy was undertaken, and subsequent histological examination of the tumor disclosed anaplastic carcinoma of the pancreas head. The carcinoma components contained adenocarcinoma and squamous cell carcinoma. Additionally, undifferentiated spindle or pleomorphic cells were seen in continuity with the carcinoma component. Undifferentiated neoplastic cells with rhabdoid features and with hyaline globule-like structures positive for PAS stain with diastase pretreatment were also observed. Immunohistochemically, cytoplasmic inclusions corresponding to rhabdoid features showed aggregates of vimentin. Ultrastructurally, hyaline globule-like structures corresponded to lysosomes. Finally, we report here the first case of anaplastic carcinoma of the pancreas with hyaline globule-like structures.

Adenoid basal carcinoma arising in the cervical polyp: an immunohistochemical study of stromal cells.

Adenoid basal carcinomas of the uterine cervix are uncommon neoplasms and generally run a favorable clinical course. Although it is well known that these tumors do not evoke the stromal reaction, we immunohistochemically examined a stromal reaction in a case of adenoid basal carcinoma. A 40-year-old woman was found to have a cervical polyp during a medical checkup and underwent polypectomy. Histological examination revealed the finding of adenoid basal carcinoma. Immunohistochemically, a smaller number of CD34-positive and CD31-negative stromal cells, namely fibroblasts, in the stroma of tumor center than in normal cervical stroma were observed. On the other hand, alpha-smooth muscle actin-positive and h-caldesmon-negative stromal cells, namely myofibroblasts, were completely absent in the stroma of tumor center. Finally, our preliminary report suggests that the decrease of CD34-positive fibroblasts in adenoid basal carcinoma may show an early stromal reaction to tumor invasion. Gynecologists and pathologists should bear in mind that adenoid basal carcinoma may arise in a cervical polyp.

Invasive ductal carcinoma of the breast with signet-ring cell and mucinous carcinoma components: diagnostic utility of immunocytochemistry of signet-ring cells in aspiration cytology materials.

Breast cancer with signet-ring cells is very rare. In this article, we present a case of invasive ductal carcinoma with signet-ring cells and mucinous carcinoma components, which could be diagnosed as a primary cancer by immunocytochemical study of fine-needle aspiration cytology material. A 73-yr-old Japanese woman noticed a palpable mass in the left breast. The aspiration cytology disclosed the monotonous proliferation of signet-ring cell with cytological atypia. The immunocytochemical examination of neoplastic cells showed a positive reaction for estrogen receptor. The extensive examination of body before the operation did not disclose any tumors in other anatomic sites. The histological examination of surgically resected breast tumor showed invasive ductal carcinoma with foci of signet-ring cell and mucinous carcinomas. Finally, our preliminary report suggests that immunocytochemical examination of aspiration cytology materials may provide useful information in searching the primary site of breast carcinoma with signet-ring cells.

Hyaline globule-like structures in undifferentiated sarcoma cells of malignant müllerian mixed tumor of the fallopian tube.

Malignant müllerian mixed tumors (MMMTs) of the fallopian tube are very rare neoplasms, and we present such a case with unusual findings here. A 57-year-old Japanese woman, after she received a medical checkup, underwent salpingo-oophorectomy on the suspicion of ovarian cancer. At the time of operation, the main tumor was present predominantly in the fallopian tube. Microscopically, the tumor consisted of carcinoma and sarcoma components. The carcinoma showed moderately to poorly differentiated adenocarcinoma. The sarcoma consisted of predominantly undifferentiated sarcoma and focally rhabdomyosarcomatous cells with abundant eosinophilic cytoplasm. Immunohistochemically, the differentiation toward rhabdomyosarcoma was confirmed. Interestingly, the cytoplasm of undifferentiated sarcoma cells contained hyaline globule-like structures. These structures showed a positive reaction for PAS, and these structures were not digested by the diastase pretreatment. Ultrastructurally, hyaline globule-like structures corresponded to lysosomes. Finally, pathologists should keep in mind that undifferentiated sarcoma cells in MMMT of the fallopian tube may contain hyaline globule-like structures in the cytoplasm.

Anal canal adenocarcinoma with MUC5AC expression suggestive of anal gland origin.

Anal canal adenocarcinomas arising in the anal ducts or glands are very rare neoplasms, and few useful immunohistochemical markers of these carcinomas are known to date. A 57-year-old man presented with anal bleeding, difficulty of defecation, and anal pain. Macroscopic findings of the surgically resected material showed circular stenosis of the anal canal. The mucosal surface was generally intact, but focal ulceration was seen. Microscopically, the proliferation of adenocarcinoma cells with mucin production was observed in the submucosal and muscular layers. The special stains of periodic acid-Schiff (PAS) and Alcian blue confirmed the presence of neutral and acid mucin. Immunohistochemically, normal rectal-type mucosa and normal anal ducts/glands showed the patterns of cytokeratin 7 (CK7)(-)/CK19(+, focal)/MUC5AC(-) and CK7(+, diffuse)/CK19(+, diffuse)/MUC5AC(+, focal), respectively, and neoplastic cells showed the pattern of CK7(+, diffuse)/CK19(+, diffuse)/MUC5AC(+, focal). Finally, our preliminary report suggests that the immunohistochemical combination of CK7, CK19, and MUC5AC may be an available marker for adenocarcinoma of anal ducts/glands origin.

Granular cell tumor arising metachronously in the bronchus and esophagus.

We present a case of granular cell tumor (GCT) occurring in the esophagus 7 years after operation for bronchial GCT. A 59-year-old Japanese man complained of epigastralgia, and endoscopic examination of the upper digestive tract disclosed a submucosal tumor in the lower esophagus. Histological examination of the endoscopic mucosal resection of the esophageal tumor showed a proliferation of neoplastic cells with an eosinophilic and granular cytoplasm. The cytoplasm of the neoplastic cells was histochemically positive for PAS stain and immunohistochemically positive for S-100. This tumor did not fulfill any of the diagnostic criteria for malignancy at either the macroscopic or microscopic level. I believe that this is the first case of GCT occurring metachronously in the respiratory and digestive tracts. Clinicians and pathologists should bear in mind that GCT may arise metachronously in the respiratory and digestive tracts.

Myofibroblasts in the stroma of metastatic pulmonary calcification in a patient with chronic renal failure.

We present a case of metastatic pulmonary calcification. Histologically, deposition of hematoxyphilic materials was seen along the alveolar and vessel walls. Fibrous tissues were also seen within the alveolar lumens, resulting in intra-alveolar fibrous pneumonia. Immunohistochemically, CD34-positive perivascular adventitial fibroblasts were seen in normal alveolar septa, whereas no myofibroblasts were observed. In contrast, perivascular adventitial fibroblasts were absent in the alveolar septa of the lesion of metastatic calcification, whereas many myofibroblasts were present in the fibrous tissue within alveolar lumens. No positive cells for TGF-(beta1) were observed in the lesion of metastatic calcification, but positive cells for PDGF-BB were focally seen in adveolar epithelial cells. Finally, many myofibroblasts appear in the alveolar lumens of metastatic pulmonary calcification, and we suggest that these myofibroblasts may be derived from CD34-positive perivascular adventitial fibroblasts and PDGF-BB may be involved in the pathogenesis of surrounding fibrosis.

Invasive micropapillary carcinoma of the urinary bladder: an immunohistochemical study of neoplastic and stromal cells.

A 66-year-old man complained of hematuria. A cystoscopy revealed a non-papillary tumor and radical cystectomy was performed. Macroscopically, an ulcerative lesion was observed. Microscopically, the neoplasm showed a mixture of urothelial carcinoma, squamous cell carcinoma and micropapillary carcinoma. Immunohistochemically, micropapillary carcinoma cells were positive for cytokeratins 7 and 20, carcinoembryonic antigen and CA125. Additionally, myofibroblasts were distributed in a chicken-wire pattern in the stroma of micropapillary carcinoma. Subsequently, the patient died of carcinoma 1 year after the onset of symptoms. Our results support the previous hypothesis that bladder micropapillary carcinoma runs an aggressive clinical course and suggest that micropapillary carcinoma may show the glandular differentiation of urothelial carcinoma and show the stromal reaction by myofibroblasts resembling that of carcinoma in other anatomic sites.