An Unexpected Surge in Plasma BKPyV Viral Load Heralds the Development of BKPyV-Associated Metastatic Bladder Cancer in a Lung Transplant Recipient With BKPyV Nephropathy.

We report a lung transplant recipient who developed BK polyoma virus (BKPyV) DNAemia and BKPyV nephropathy. With careful management of his immunosuppression he achieved significant reduction in BKPyV DNAemia and stabilization of his kidney function. He later developed a high-grade bladder cancer and shortly thereafter he experienced a major upsurge in the level of BKPyV DNAemia that coincided with the discovery of hepatic metastasis. Retrospectively, the bladder cancer and the hepatic secondary tumor stained uniformly for SV40 large T antigen, and the BKPyV DNA sequences identified in plasma corresponded to BKPyV DNA within hepatic tissue, indicating that the spike in BKPyV load was likely derived from the circulating tumor cells or cell-free tumor DNA following metastases of a BKV-associated cancer. To the best of our knowledge, this is the first description of a surge in BKPyV load in a patient with controlled BKPyVN that heralded the appearance of a metastatic urothelial malignancy. This report discusses the literature on BKPyV-associated malignancies and the possibility that unexplained increases in BKPyV DNAemia may be a biomarker for metastatic BKPyV-related urothelial cancer.

BK Polyomavirus Infection and Renourinary Tumorigenesis.

BK polyomavirus (BKPyV) infection represents a major problem in transplantation, particularly for renal recipients developing polyomavirus-associated nephropathy (PyVAN). The possibility that BKPyV may also be oncogenic is not routinely considered. Twenty high-grade renourinary tumors expressing polyomavirus large T antigen in the entirety of the neoplasm in 19 cases, including the metastases in six, have been reported in transplant recipients with a history of PyVAN or evidence of BKPyV infection. Morphological and phenotypical features consistent with inactivation of the tumor suppressors pRB and p53 were found in the bladder tumors, suggesting a carcinogenesis mechanism involving the BKPyV large tumor oncoprotein/antigen. The pathogenesis of these tumors is unclear, but given the generally long interval between transplantation and tumor development, the risk for neoplasms after BKPyV infections may well be multifactorial. Other elements potentially implicated include exposure to additional exogenous carcinogens, further viral mutations, and cell genomic instability secondary to viral integration, as occurs with the Merkel cell PyV-associated carcinoma. The still scarce but increasingly reported association between longstanding PyVAN and renourinary neoplasms requires a concerted effort from the transplant community to better understand, diagnose, and treat the putative association between the BKPyV and these neoplasms.

Expression of c-erbB-2 oncogene and p53 tumor suppressor gene in benign and malignant breast tissue: correlation with proliferative activity and prognostic index.

The expression of c-erbB-2 oncogene and p53 tumor suppressor gene was studied in methacarn-fixed, paraffin-embedded biopsy specimens from 58 benign breast lesions and 129 sporadic breast carcinomas, using the supersensitive monoclonal antibodies CB 11 and BP 53-12-1 and the biotin-streptAvidin-amplified methodology. None of the benign lesions studied, which included 36 fibrocystic lesions with mild or florid epithelial hyperplasia, 12 fibrocystic lesions with ADH or ALH and 10 fibroadenomas, demonstrated membrane staining for c-erbB-2 or nuclear immunoreactivity for p53. Overall, 48.06% of primary breast carcinomas showed membrane expression of c-erbB-2, while 28.68% were p53 positive. Those showing p53 immunoreactivity displayed a nuclear and/or cytoplasmic staining type. A significant correlation was seen between c-erbB-2 and p53 expression (r = 0.213, p < 0.05), as well as between c-erbB-2 status and PSNA score (r = 0.221, p < 0.05). In addition, c-erbB-2 and p53, separately or in combination, correlated significantly with the prognostic index. In conclusion, immunohistochemistry of c-erbB-2 and p53 immunohistochemistry allows a better definition of intraductal proliferative lesions and assists in the differentiation between ADH and DCIS. It provides additional clues with regard to the biologic behavior of invasive ductal carcinomas (NOS and medullary).

Localization of p53 and proliferating cell nuclear antigen in fine-needle aspirates of benign and primary malignant tumors of the human breast: an immunocytochemical study using supersensitive monoclonal antibodies and the biotin-streptavidin-amplified method.

p53 and proliferating cell nuclear antigen (PCNA) status was determined in fine-needle aspirates (FNAs) and methacarn-fixed paraffin-embedded tissue sections of six fibroadenomas and 50 primary breast carcinomas using supersensitive monoclonal antibodies and the biotin-streptavidin-amplified method. Nuclear accumulation of p53 was identified in 28% of carcinomas, while a heterogeneous immunostaining for PCNA was seen in all benign and malignant tumors examined. p53 expression in relation to nuclear plemorphism and lymph-node status showed weak correlation only as to nuclear grade (r = 0.28; P < 0.01). No direct or inverse correlation was found to exist between PCNA score and the evaluated prognostic parameters. In conclusion, although the identification of p53 in FNAs of breast tumors may assist in the diagnosis of malignancy, its application in the laboratory practice of cytopathology appears to be limited, since only 28% of primary breast carcinomas accumulate p53. Moreover, PCNA immunocytochemistry can be used as an alternative to traditional methods of evaluating the proliferative rate of tumors in FNAs.

Three cases of primary malignant melanoma of the alimentary tract.

The malignant melanomas of the gastrointestinal tract, especially their achromatic variants, are rare primary tumors, causing certain diagnostic problems. We report three cases of primary malignant melanomas (two of them being achromatic) of the small intestine and anal canal in patients in their fifth decade of life. For precise diagnosis, a parallel investigation was conducted using histology, histochemistry, immunohistochemistry, and electron microscopy. Consideration is also given to the mechanism of these tumors.

Glycogen-rich clear cell carcinoma of the breast: report of a case with fine-needle aspiration cytology and immunocytochemical and ultrastructural studies.

Fine-needle aspiration cytology, immunocytochemistry, and electron microscopic findings are described in a case of glycogen-rich clear cell carcinoma of the breast. The aspirate contained many small and large papillary cell groups and numerous single tall columnar cells with apical cytoplasmic projections and mild to moderate degree of nuclear pleomorphism. Cytochemical localisation of glycogen and immunostaining on air-dried smears with CEA and actin monoclonal antibodies permitted the correct identification and differential diagnosis of the tumor. Electron microscopic examination of the resected specimen confirmed the diagnosis of glycogen-rich clear cell carcinoma. The differential diagnosis and potential diagnostic pitfalls are discussed, and recommendation are offered to prevent misdiagnosis.

The apocrine carcinoma of the breast. A cytological, immunohistochemical and ultrastructural study of 6 cases.

The apocrine carcinoma is a rare type of invasive breast carcinomas. Characteristic features of this neoplasm are shown by the eosinophilic granular cytoplasm with apical snouts and strong expression of GCDFP-15. A review of 2000 available primary breast carcinomas identified 6 examples (0.3%) based on the definition. Architecturally, these tumors displayed either a solid-tubular or a papillary growth pattern, while cytologically the lesions were composed of large columnar epithelial cells with marked anisonucleosis and numerous PAS-positive diastase-resistant cytoplasmic granules. Immunohistochemically, apocrine breast carcinomas showed abundant GCDFP-15, CEA an c-erbB-2 oncoprotein. Electron microscopic analysis revealed the presence of numerous secretory granules. The differential diagnostic problems of apocrine breast carcinomas and malignant tumors mimicking them are discussed.

Immunocytochemical detection of carcinoembryonic antigen in fine-needle aspirates from patients with diverse breast diseases.

Fine-needle aspirates and paraffin-embedded tissue sections from 91 cases with diverse breast diseases were immunostained with carcinoembryonic antigen (CEA) monoclonal antibody using a BioGenex StrAviGen kit based on the biotin-streptavidin amplified methodology. The results were compared with histopathologic tumor type and tumor stage. CEA was not expressed in fibrocystic changes with mild or florid epithelial hyperplasia (n = 23) and fibroadenomas (n = 8). On the other hand, 90% (56/60) of primary breast carcinomas showed positive cytoplasmic staining for CEA. No correlation was found between CEA expression, histopathologic tumor type, and tumor stage. We suggest that CEA immunocytochemistry will help in the accurate diagnosis of primary breast carcinoma in fine-needle aspirates in addition to the usual cytological criteria.

[Immunohistochemical evidence of vimentin in fibrocystic breast disease and mammary carcinoma]. / Immunhistochemischer Nachweis von Vimentin bei fibrozystischen Mastopathien und Mammakarzinomen.

Immunohistochemical investigations were conducted of cryostat sections taken from 25 cases of fibrocystic breast disease and 100 cases of mammary carcinoma (among them 15 cases with lymph node metastases) to obtain information on expression of vimentin. Immunoreactive epithelial cells were recordable from 12 cases of fibrocystic disease (48%) and 32 tumors (32%). In the majority of all cases with vimentin-expressing carcinoma, positive staining was exhibited by less than 10% of the neoplastic cells. No correlation was found to exist between histological tumor grade, lymph node status and vimentin expression.

Carcinosarcoma of the breast. Immunohistochemical and ultrastructural studies.

A case of a carcinosarcoma in the breast of a 51-year-old woman is described. The tumor consisted of two diversely differentiated components with cells possessing epithelial and mesenchymal characteristics. Plenty of cytokeratin and CEA were immunohistochemically recordable from the carcinomatous component. Some neoplastic cells also stained positively for actin, S-100 protein and smooth muscle antigen. The sarcomatous component was positive only for vimentin. Electron microscopic analysis revealed presence of the following cell types: epithelial cells, myoepithelial cells and polymorphous mesenchymal cells.

[Diffuse malignant mesothelioma of the pericardium]. / Diffuses malignes Mesotheliom des Perikards.

Reported in this paper is the morphological appearance of a diffuse malignant mesothelioma in a male patient aged 39 years. The tumour parenchyma was primarily made up of fusiform and giant cells. Glandular structures were rarely observed. Immunohistochemical investigation revealed negative staining for CEA and positive staining for vimentin.

[Non-Hodgkin's lymphoma of the thyroid gland. Morphologic and immunohistochemical findings in 2 cases]. / Non-Hodgkin-Lymphom der Schilddrüse. Morphologische und immunhistochemische Befunde bei 2 Fällen.

Described in this paper are two cases of non-Hodgkin lymphoma (NHL) of the thyroid gland in women with Hashimoto's thyroiditis. NHL may be misinterpreted for its histological similarity to anaplastic thyroid carcinoma. The immunoperoxidase technique can be used with good success to confirm the lymphocytic origin of tumor cells.

[Immunohistochemical and electron microscopical study of the myoepithelium in mastopathy and carcinoma of the mammary gland]. / Immunhistochemische und elektronenmikroskopische Untersuchung der Myoepithelien bei Mastopathien und Karzinomen der Milchdrüse.

Biopsies obtained from 45 cases of invasive ductal carcinoma and 41 cases of cystic mastopathy were immunohistochemically investigated, with electron microscopy being used on some of them, for the purpose of clearing up presence, distribution, and ultrastructural peculiarities of the myoepithelial cells. Focal or diffuse myoepithelial proliferations were observed in all cases of cystic mastopathy, with peripheral layers of myoepithelium at the basal membrane being widely preserved. Myoepithelial cells had lost their normal position and cellular orientation in the regions with intraductal carcinoma. Actin-positive, high-microfilament myoepithelial cells were frequent findings recorded from parenchyma in cases of invasive ductal carcinoma without specific differentiation, though cells of that kind were rarely detectable from parenchyma in cases of medullary carcinoma. Particular attention should be given to the presence of tumor cells differing from each other for their morphological and functional differentiation in cases of carcinoma of the mammary gland.

[Metastasis from tumor to tumor]. / Metastasen von Tumor zu Tumor.

Reported in this paper are two autopsy cases in which metastases were recorded from oat-cell carcinomas of the lung to other tumors. In one case, formation of metastases was extended into a hamartochondroma of the other lung, while an adenocarcinoma of the pancreas was affected in the other. Different possible explanations for the phenomenon observed are discussed, and particular reference is made to the important role played by autopsy in accurate investigation of interrelations between coexisting tumors.

A new substance effective against transplantable tumors in vivo: L-cystine-bis-(N,N-beta-chloroethyl)-hydrazide.

It is shown that L-cystine-bis-(N,N-beta-chloroethyl)-hydrazide-hydro-bromide possesses strong (50-100%) inhibitory effect in vivo against myeloma P-8, carcinosarcoma Walker, lymphosarcoma Pliss, sarcoma Yoshida, sarcoma Jensen and sarcoma 180 in doses 5-12 mg/kg/day. No suppression of the growth of Ehrlich ascites tumor was observed. The acute toxicity (LD50) of this substance on mice and rats is 71 mg/kg and 47 mg/kg respectively.