International Journal of Surgical Pathology

Activation of ret/IPTC-1 has been documented in a minority of papillary thyroid carcinomas (PTC). In a recent study, the authors' group detected the presence of ret/IPTC-1 in association with a background of florid lymphocytic thyroiditis (LT) in 58% of cases of PTC studied, which prompted them to examine the incidence of RET/PTC-1 expression in 27 examples of various forms of nonlymphomatous lymphoid infiltration of the thyroid by using TaqMan RT-PCR. Overall, 21 cases (78%) were found to express the chimeric transcript of ret/IPTC-1. Eighteen cases of Hashimoto thyroiditis were positive (95%), and, of these, three had concomitant PTC while the remainder had no histologic evidence of associated malignancy. Three cases of lymphocytic thyroiditis demonstrated activated ret/PTC-1 (43%), two having associated PTC. These data suggest either that ret/PTC-1 is an indicator of follicular thyroid cell activation or that ret/PTC-1 activation is an early event in malignant transformation. If the latter is the case, it may be that, in a defined subset of the cell population, ret/IPTC-1 activation elicits an autoimmune response, which, while possibly curtailing the development of PTC in the majority of cases, results in destruction of the thyroid parenchyma.

Adhesion molecules are transmembrane glycoproteins mediating cell-cell and cell extracellular matrix interactions. They control a number of fundamental biological processes including cell migration, differentiation, proliferation, and apoptosis. In the last decade there has been an increasing interest in the exploitation of these molecules as diagnostic and/or prognostic markers in tumor pathology. For example, a large number of studies have shown that loss of E-cadherin expression correlates with high tumor grade and advanced tumor stage in a number of malignancies. The analysis of adhesion molecule profile in a routine clinical setting needs further investigation in prospective multicenter studies.

In this study based on the study of a centromeric DNA probe specific for chromosome 8 the authors standardized a method for the enzymatic detection of specific chromosome copy numbers on interphase nuclei from tumor tissue samples. Since the in situ hybridization (ISH) of chromosome 8 specific probe was revealed with a catalyzed reporter deposition (CARD), which allows a high amplification of the hybridization signal, the method was designated as CARD-ISH. This method has been standardized on interphase nuclei isolated from clinical samples of pituitary adenomas, as well as on human normal lymphocytes. On the same samples, they also evaluated chromosome 8 copy number distribution by FISH. Comparison between CARD-ISH and FISH results showed no significant differences between the two methods, proposing CARDISH as a reliable alternative to FISH for chromosome numerical aberration assessment in laboratories that do not have specific facilities for epifluorescence microscopy or cytogenetics and that need a long-term storage of slides that had been used for diagnostic purposes.

Although clinically associated with von Hippel-Lindau (VHL) disease, the pathogenesis of papillary tumors of the broad ligament, epididymis, and peritoneum arising in patients with VHL disease is not clear. The “classic” VHL-associated neoplasms, including hemangioblastoma and renal cell carcinoma, have been found to be associated with the inactivation of both VHL gene copies. It is not known whether a similar inactivation of the VHL gene is also responsible for the development of these uncommon VHL-associated lesions. The authors performed PCR (polymerase chain reaction) and PCR-based SSCP (single-strand conformation polymorphism) analysis on five predominantly papillary tumors in five VHL patients (one papillary cystadenoma of the broad ligament, one endometrioid cystadenoma of the broad ligament, two papillary cystadenomas of the epididymis, one papillary tumor of the retroperitoneum) with four polymorphic markers of VHL gene (D3S1038, D3S1110, D3S2452, 104/105). All five tumors showed allelic loss of VHL gene. The results provide the first genetic evidence for the role of VHL gene in the tumorigenesis of these rare benign neoplasms and confirm these tumors as phenotypic manifestations of VHL disease.

Mutations of the p53 tumor suppressor gene often occur in a variety of human malignant tumors and are frequently associated with overexpression of p53 protein. This study was designed to examine indirectly the frequency of p53 protein in primary endometrial carcinoma and to correlate the overexpression with steroid hormone receptor status including pS2 protein status. The study was performed on 79 formalinfixed, paraffin-embedded tissues of endometrial carcinoma. P53 protein overexpression was detected by means of immunohistochemistry using monoclonal antibody NCL-p53-D07. Estrogen and progesterone receptor status was determined by immunohistochemistry using the monoclonal antibodies NCL-ER-LH₂ and NCL-PGR, respectively, and the pS2 protein using polyclonal antibody NCL-pS2. Overexpression of p53 protein was found in 27 (34%) of the 79 endometrial carcinomas. A strong positive relationship was demonstrated between histologic grade and p53 protein overexpression. There was a significant correlation between p53 protein overexpression and negative estrogen receptor status (49%) negative progesterone receptor status (49%) as well as a negative pS2 protein (45%). The results suggest that overexpression of p53 is associated with high malignant potential. However, p53 overexpression itself does not appear to be an independent prognostic factor in endometrial carcinomas.

This report draws attention to two unusual features of the stromal component of endometriosis that can create problems in diagnosis. One of these is the exclusive presence of endometriotic stroma, so-called stromal endometriosis, that can occasionally take the form of microscopic nodules of endometriotic stroma on the pelvic peritoneum and other locations. This finding, which we refer to as a micronodular stromal endometriosis, can be overlooked entirely or lead to confusion with peritoneal involvement by low-grade endometrial stromal sarcoma. The other finding we describe is the presence of a prominent elastotic stromal response to endometriosis that can occasionally obscure or even focally obliterate the typical endometriotic stroma. This finding, although nonspecific, can be a diagnostic clue to the presence of endometriosis, especially when accompanied by the presence of the typical endometriod glands of that lesion.

Breast fine needle aspiration (FNA) biopsy accounted for 6% of surgical pathology and FNA claims reviewed from 1995-97. The majority of these claims were for false negative breast FNA resulting from sampling error in a woman with a palpable breast mass. Controversies concerning the definition of specimen adequacy for breast FNA are discussed and a strategy for minimizing the management and liability consequences of the problem is proposed. Claims for false positive breast FNA usually result from interpretive error.

The sex cord tumor with annular tubules was discovered as a distinctive entity when its unusualappearing microscopic pattern was encountered repetitively in a pathology consultation practice. The author was stimulated to describe the clinicopathological features of the tumor and assign it a specific name when a minority of the cases in his series were found to be associated with the rare Peutz-Jeghers syndrome. Both these tumors and those occurring in the absence of the syndrome have been shown to have distinctive clinicopathological features that differ from those of other tumors in the sex cord-stromal category.

The nasopharyngeal lymphoid tissue (adenoids) is an uncommonly reported primary site for Hodgkin's disease. We report a case of primary adenoidal, interfollicular, epithelioid cell-rich variant of mixed cellularity Hodgkin's disease. The combination of an interfollicular pattern and richness of epithelioid histiocytes made it very difficult to make the diagnosis of Hodgkin's disease without the help of immunohistochemistry. To our knowledge, only 39 cases of Hodgkin's disease primarily involving the Waldeyer's ring have been reported in the English literature, 24 of these primarily involving the adenoids. Our case shows the difficulty encountered in making the diagnosis when a very unusual morphologic appearance of Hodgkin's disease is seen at a rare presentation site. The appropriate immunohistochemical work-up should be performed in unusual lymphohistiocytic proliferations involving the Waldeyer's ring.

A case of melanotic neuroectodermal tumor of infancy (MNTI) in a 6-months-old white female child is presented. The tumor was located in the left half of the superior maxillary bone and affected the maxillary sinus, inducing large facial asymmetry. The histologic aspects of the tumor were typical for the entity: two cell populations, one pigmented melanocyte-like cell, the other small neuroblastic-like cell. After adjuvant chemotherapeutic treatment with a strong reduction of the tumor, the melanocytelike cell predominated, allowing a better result of the surgery and probably a better prognosis.

We describe the case of a 62-year-old man with chronic irritation of the urinary bladder resulting in dysuria and hypogastric pain. Three neoplasms measuring 0.5, 1, and 1.5 cm, respectively, were observed by cystoscopy and removed by transurethral resection (TUR). Histologic examination showed a complex folding of squamous hyperplastic epithelium around a connective tissue core. The superficial epithelium contained numerous koilocytes. The double polymerase chain reaction (PCR) detected DNA of type 11 human papillomavirus (HPV). The diagnosis was condyloma acuminatum of bladder. Three months later the patient presented with fever, and a new cytoscopy demonstrated an ulcerated, exophytic 4.5 cm mass. Histopathology showed a squamous carcinoma with papillomatous structure, pronounced viral koilocytosis, and irregular invasive deep margin. HPV type 11 was found with double PCR. The diagnosis was warty carcinoma arising in condyloma acuminatum. To the best of our knowledge, this is the first case of warty carcinoma of the urinary bladder described in the literature. We discuss the relationship between the infection by HPV and the development of condyloma acuminatum, its evolution toward a well-differentiated squamous carcinoma, and its distinction from verrucous carcinoma.