CD13-positive anaplastic large cell lymphoma of T-cell origin--a diagnostic and histogenetic problem.

The expression of myelomonocytic-associated antigens in anaplastic large cell lymphomas (ALCLs), particularly those presenting in extranodal sites, can make their distinction from extramedullary myeloid cell tumors (EMCTs) or histiocytic tumors problematic. Yet, this distinction is clinically significant because of its therapeutic and prognostic implications. Herein, we describe a case of extranodal anaplastic lymphoma kinase-positive CD30-positive ALCL of T-cell origin in a 12-year-old boy, which was initially called an EMCT because of the expression of CD13 and HLA-DR detected by flow cytometry and the absence of other T-cell-related surface markers. However, the detection of cytoplasmic CD3 by flow cytometry prompted further studies. The tumor was composed of large cells with abundant slightly eosinophilic vacuolated cytoplasm and ovoid or reniform nuclei with a few small nucleoli. Using immunohistochemistry, the tumor was positive for CD45, CD30, CD45RO, and CD43 with a strong cytoplasmic and nuclear anaplastic lymphoma kinase stain. The tumor cells showed a T-cell clonal genotype. Electron microscopy revealed no ultrastructural features of myelomonocytic or histiocytic origin. The patient responded well to the chemotherapy and was in complete remission for 10 months at the time of submission of this manuscript. Review of the literature showed inconsistencies regarding the diagnosis, nomenclature, and, therefore, treatment and prognosis of these tumors. In addition, the CD13 expression in ALCL raises some histogenetic questions and may indicate origin from a pluripotent stem cell, misprogramming during malignant transformation, or a microenvironmental effect on lymphoid cell expression of surface antigens. Therefore, ALCL should be considered in the differential diagnosis of EMCTs or histiocytic tumors, particularly when surface marker lineage assignment is ambiguous.

Immunohistochemical localization of prostate-specific antigen in ductal epithelium of male breast. Potential diagnostic pitfall in patients with gynecomastia.

Enlargement of the male breast is frequently encountered in the course of adjuvant antiandrogen therapy for advanced prostate carcinoma. The clinical differential diagnosis in this setting includes hormonal imbalance-induced gynecomastia, primary breast carcinoma, and metastasis of prostatic carcinoma. Biopsy of the lesion with the identification of prostate-specific antigen (PSA) plays an important role in establishing the correct diagnosis. Recent studies showed that female mammary epithelium may be a significant source of PSA, but its expression in male breasts has not been sufficiently studied. We found that normal and hyperplastic duct epithelium in gynecomastia exhibited focal, strong (+3) PSA immunoreactivity in 5 of 18 cases (28%). In contrast, no PSA reactivity was found in eight cases of male breast carcinoma. No reactivity was seen with antiprostatic acid phosphatase (PsAP) antibody, in either benign or malignant epithelium. Frequent expression of PSA in gynecomastia may, in an appropriate clinical setting, cause confusion with metastatic prostatic carcinoma. The lack of immunoreactivity for PsAP in male breast epithelium indicates its usefulness in the differential diagnosis.

Extramammary Paget disease is characterized by the consistent lack of estrogen and progesterone receptors but frequently expresses androgen receptor.

Extramammary Paget disease (EPD) is an uncommon cutaneous malignant neoplasm that arises in areas rich in apocrine glands (perineum, vulva, and axilla). Apocrine gland origin or apocrine differentiation of cells of EPD has been suggested. Estrongen, progesterone, and androgen hormone receptors have been reported to exhibit a characteristic pattern of expression in mammary apocrine type carcinomas; however, their expression in EPD has not been elucidated fully. By using immunohistochemical methods, we studied the expression of steroid receptors in EPD on formalin-fixed paraffin-embedded tissue samples from 28 patients with EPD without associated visceral malignant neoplasms or adnexal carcinoma. Androgen receptor (AR) was identified in 15 of 28 cases. The proportion of AR-positive cells varied from 1% to more than 75%; 8 cases expressed AR in more than 10% of cells. Strong AR expression also was seen in the invasive carcinoma arising from 1 case of EPD. All cases lacked immunohistochemically detectable estrogen and progesterone receptors. The immunophenotype characteristic of apocrine carcinomas (AR-positive, estrogen receptor-negative, progesterone receptor-negative) was seen in a substantial proportion of EPD cases. Results suggest that AR expression is a factor in pathogenesis of EPD. This may be important for the therapy of recurrent or invasive disease.

The expression of Fhit protein is related inversely to disease progression in patients with breast carcinoma.

BACKGROUND: The FHIT gene, located at human chromosome 3p14.2, frequently is deleted in a number of human tumors, including breast carcinoma. Its protein product (Fhit) is presumed to have tumor suppressor function. Loss of expression of a tumor suppressor gene is an important step in tumor progression from premalignant, to in situ, to invasive carcinoma. METHODS: In the current study, Fhit expression was examined in invasive carcinomas and in epithelial lesions representing stages of carcinoma progression in 50 mastectomy specimens using immunohistochemical methods. RESULTS: Normal ductal and lobular epithelium consistently and strongly expressed Fhit. A complete loss of or a significant reduction in Fhit expression was observed in 72% of breast carcinomas. A statistically significant, negative correlation in Fhit expression among the stages of disease progression in Fhit negative breast carcinomas was observed (normal epithelium > hyperplasia > atypical hyperplasia and carcinoma in situ > invasive carcinoma), whereas no loss of Fhit expression in precursor lesions was observed in Fhit positive tumors. CONCLUSIONS: These observations are consistent with the observed role of FHIT as a tumor suppressor gene in the pathogenesis of specific subsets of carcinomas.

Different immunohistochemical patterns of Fhit protein expression in renal neoplasms.

BACKGROUND: The FHIT gene on human chromosome 3p14.2 is deleted in a variety of malignant tumors, including clear cell renal carcinomas (RCCs) resulting in a loss of expression of Fhit protein. The Fhit expression in specific subtypes of renal carcinomas has not been characterized. We have investigated the association of Fhit expression with particular subtypes of renal tumors to determine the role and specificity of this putative tumor suppressor gene in renal neoplasia. MATERIAL AND METHODS: The immunohistochemical expression of Fhit was tested in normal kidneys and in 109 renal neoplasms consisting of 51 clear cell RCCs, 26 papillary RCCs, two chromophobe carcinomas, six oncocytomas, four pelvic transitional cell carcinomas and 20 Wilms' tumors from formalin fixed and routinely processed tissue. RESULTS: Normal renal tubules expressed Fhit strongly and consistently. The majority (78%) of clear cell RCCs showed reduced or absent expression of Fhit, whereas the majority (74%) of papillary carcinomas, all chromophobe renal cell carcinomas, and oncocytomas were strongly positive. Sixty-eight percent of low-grade (G1 plus G2) but only 9% of high-grade (G3 plus G4) clear cell carcinomas were Fhit negative. Wilms' tumors demonstrated focal staining in the epithelial component in 8 of 20 cases (40%). CONCLUSIONS: The loss of Fhit expression in a high percentage of clear cell RCCs with conservation of Fhit in other types of tumors supports the proposed role of FHIT alterations in the genesis of clear cell carcinomas in contrast to other types of renal epithelial tumors. FHIT expression may play a role in epithelial differentiation of nephroblastomas (Wilms' tumors).