Victor G. Prieto

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.

Melanoma of the gallbladder: a review of cases seen at Duke University Medical Center.

Both primary and metastatic melanoma of the gallbladder are rare. In cases involving isolated tumors of the gallbladder, there continues to be controversy regarding the establishment of primary status. Despite appropriate therapy, the diagnosis of either condition portends a poor prognosis, with few patients surviving more than 2 years.

Correlating architectural disorder and cytologic atypia in clark (dysplastic) melanocytic nevi

Histological architecture is very important in the pathological diagnosis of Clark (also known as atypical or dysplastic) melanocytic nevi. However, few studies have attempted to quantify architectural features or to correlate them directly with cytology. In 166 consecutive Clark nevi, the presence or absence of the following features in the intraepidermal or junctional component was recorded: (1) Architecture: circumscription, symmetry, cohesiveness of nests, suprabasal melanocytes, confluence, and single-cell proliferation; (2) Cytology of melanocytes: round/euchromatic nuclei, nuclear enlargement, cell enlargement, and prominent nucleoli. Each criterion was given a value of 0 or 1, and a summation score was obtained for both architecture and cytology in each case. The chi-square test was used to determine the significance of relationships among these parameters. The degrees of architectural disorder and of cytologic atypia were positively correlated (P = .026). Scores for both parameters were distributed over a wide range of values and were concentrated toward the low-middle portion of the spectrum. Several particular architectural and cytologic variables showed significant interdependence. Clark nevi exhibit a broad spectrum of architectural disorder and cytologic atypia, which, according to our data, generally are closely related features. Because some cases displayed a relatively high score for one parameter but a low score for the other, quantification of both parameters permits a more complete histopathologic evaluation of these lesions and may provide additional information for their clinical management.

Epstein Barr virus‐associated lymphoproliferative‐disorders primarily involving the skin

In cases of solid organ or bone marrow transplantation, up to 2 to 10% of patients may develop lymphoproliferative disorders (LPD), often induced by Epstein‐Barr virus (EBV). Despite a morphology mimicking malignant lymphoma, in some cases the lesions will disappear completely after the degree of immunosuppression is lowered. Lately, similar processes have been described in non‐transplant, immunosuppressed patients. A SNOMED search was performed on the database of three hospitals between 1990 and 1997, to identify patients with immunosuppression‐relaied lymphoproliferative disorders (IR‐EPD) involving primarily the skin. Two patients were identified. One was 2 years after kidney transplantation, and the other was being treated with methotrexate for dermatomyositis. In both biopsies, there was a diffuse perivascular proliferation of large lymphocytes with ample cytoplasm and pleomorphic nuclei, associated with extensive dermal and subcutaneous necrosis. Immunohistochemical studies revealed expression of CD20, CD45RO, CD43, CD30, EBV‐LMP1, and EBV‐NA2 by the atypical lymphocytes in both cases and, in one case, of the EBV‐transcriptional replication activation protein. In both cases the lesions completely disappeared and have not recurred. Primary involvement of the skin by IR‐LPD is very rare. Based on our results, it is possible that some of these cases in the skin contain EBV and co‐express CD30 and T‐ and B‐ccll markers. The diagnosis of IR‐LPD should be considered in cutaneous lymphoid proliferations in immunosuppressed patients. Belore rendering an unequivocal diagnosis of malignant lymphoma, reduction of immunosuppression and follow‐up of 4‐8 weeks should be considered.

Immunohistochemistry of dermatofibromas and benign fibrous histiocytomas

Dermatofibromas (DF) are common, benign skin tumors composed predominantly of cells having elongated nuclei and very scant cytoplasm (i.e., fibroblasts) and capillaries in a collagenous stroma. Some authors distinguish DF from benign fibrous histiocytomas (BFH), which are composed of cells with round to oval nuclei and abundant cytoplasm (i.e., histiocytes). In general, this group of tumors expresses factor XIIIa but not the antigen recognized by MAC 387. However, immunohistochemical differences specifically between DF and BFH have not been reported.

CD34 immunoreactivity distinguishes between scar tissue and residual tumor in re‐excisional specimens of dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumor that often recurs after simple excision, and therefore usually requires wide surgical re‐excision. It is sometimes difficult to distinguish histologically between residual tumor and scar tissue formed in response to the original biopsy. In an effort to solve this diagnostic problem, we have examined CD34 immunoreactivity in 10 primary biopsies of DFSP, 12 scars, and 7 re‐excisional DFSP specimens containing residual tumor adjacent to scar tissue. In all 10 primary biopsies of DFSP, the tumor cells strongly and uniformly expressed CD34. In the 12 scars, only periaclnexal cells, enclothclial cells, and rare, scattered dendritic cells in the clermis were immunolabeled for CD34. In the 7 re‐excisions of DFSP, the foci of residual DFSP were strongly immunolabeled, while the surrounding scar tissue was not. The pattern of CD34 immunoreactivity distinguishes DFSP from scar tissue, and thereby may permit more accurate assessment of surgical margins in re‐excisional specimens of DFSP.

The intermediate filament peripherin is expressed in cutaneous melanocytic lesions

Peripherin is an intermediate filament involved in growth and development of the peripheral nervous system and is localized to neurons, some other cells derived from neural tube and neural crest, and some neuroendocrine cells (e.g. β cells of islets of Langerhans). Peripherin also has been demonstrated in neuroblastomas and cutaneous neuroendocrine (Merkel cell) carcinomas. The expression of peripherin by other cells derived from the neural crest is unknown.

Trichoepithelioma: a 19‐year clinicopathologic re‐evaluation

Accurate histopathologie distinction between trichoepithelioma (TE) and basal cell carcinoma (BCC) may be challenging. From 97 cases diagnosed as TE during the period 1979–1997, 73 available cases were studied with regard to: 1) stroma; 2) retraction effect; 3) papillary‐mesenchymal bodies (PMB); 4) amyloid; 5) mitotic figures; 6) apoplotic cells; 7) inflammation; 8) granuloma; and 9) calcification. A judgment was made regarding diagnosis. The patients’medical records were subsequently reviewed for clinical features and possible recurrence. The diagnosis of TE was confirmed histologically in 48 (65%) of 73 cases. Fifteen cases (21%) were reclassified as BCC (RC‐BCC), eight other cases (11%) were reclassified as other lesions, and two additional cases (3%) could not be confidently classified as either TE or BCC. The most helpful differentiating features were the presence of retraction effect (in 100% of RC‐BCC vs. 37% of TE), myxoid stroma (in 80% of RC‐BCC vs. 12% of TE) and PMB (in 20% of RC‐BCC vs. 81% of TE). Unexpected findings in TE were detection of amyloid in 33%, apoplotic cells in 100%, and mitotic figures in 46%. Five of the 15 RC‐BCC have recurred (33%), whereas there have been no recurrences in the confirmed TE group. A constellation of hisiopathologic criteria may help lo discriminate problematic examples of trichoepithelioma from basal cell carcinoma.

Primary malignant melanoma of the esophagus

A 48‐year‐old woman presented with a 6‐month history of dysphagia, often associated with retrosternal chest pain. Upper endoscopy revealed an unusual pigmented lesion within the middle portion of the esophagus, and multiple biopsies were obtained. The histopathology and immunohistochemical profile of the tissue specimens were diagnostic of malignant melanoma. A thorough clinical and radiographic evaluation was performed, providing no additional findings or alternative primary source. Of approximately 11,500 melanoma patients entered in the Duke University melanoma database since 1970, this represents the only case of primary esophageal melanoma. The case is described and a review of the literature is presented. J. Surg. Oncol. 1997;66:201–206.

Malignant melanoma with paradoxical maturation

Typically, melanocytic nevi “mature” (i.e., exhibit a morphologic shift to smaller or spindle cells with progressive depth in the dermis). In contrast, most malignant melanomas (conventional MMs) lack maturation, and are composed of large pleomorphic cells throughout. The authors describe a series of melanomas with paradoxical maturation mimicking the pattern of nevi. Seventeen primary invasive melanomas with paradoxical maturation (IMPs), two epidermotropic metastatic melanomas with maturation (EMMMs), 13 compound nevi (CN), and 14 conventional MMs without apparent maturation were analyzed by histologic, cytomorphometric, and immunohistochemical techniques. With increasing dermal depth, both CN and IMPs had smaller nuclear and cellular areas, and decreased expression of Ki-67, glycoprotein (gp)100 (with HMB-45), and tyrosinase. IMPs had significant differences from conventional MMs; namely, smaller nuclear and cytoplasmic areas (deep), and decreased expression of Ki-67 (superficial and deep), gp100 (deep), and tyrosinase (deep). IMPs also had notable differences from CN: namely, larger nuclear and cellular areas, more confluence, more mitotic figures, increased Ki-67 and gp100 expression in both the superficial and deep portions, and more melanin (deep). The two EMMMs exhibited histologic and immunohistochemical features similar to the primary IMPs. IMP, because of its mimicry of nevus, can present a diagnostic hazard. The authors propose histologic, morphometric, and immunohistochemical criteria that facilitate recognition and accurate diagnosis of this unusual variant of melanoma.