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Notes: In evaluating histologically malignant infiltrates in the skin, it is often challenging to distinguish granulocytic sarcoma (GS) from selected cases of peripheral T-cell lymphoma (PTCL). These lesions have clinical features in common, in addition to shared histologic attributes. These include similarity in dermal distribution and growth pattern, nuclear characteristics, propensity to recruit other inflammatory cell types, and production of matrical sclerosis. In order to determine if immunohistology could contribute to differential diagnosis in this setting, we analyzed 15 cases of mucocutaneous GS, and compared them with 11 cases of well-documented PTCL. Antibodies in the CD15, CD20, CD34, CD43, GD45, CD45RO, and CD68 groups were used, as well as antimyeloperoxidase (anti-MPX), anti-lysozyme (anti-LYSO), Mac387, and MB2. Anti-LYSO and anti-MPX were sensitive and specific markers of GS, labeling 93% and 80% of GS cases, respectively, and no cases of PTCL. Anti-CD 15 and MB2 were also specific for GS, but each labeled only (50% of GS cases. CD34, CD68, and Mac 387 were specific but insensitive markers of GS. CD43 and CD45 were not particularly useful discriminants, with each being seen in 93% of GS cases, but also 64% and 100% of cases of PTCL, respectively. CD45RO was specific for PTCL; it was present in 82% of PTCL cases and no GS cases. Thus, conjoint reactivity for CD43, CD45, MPX, and LYSO characterizes GS, and differs from the pattern of PTCL, which is characterized by reactivity for CD45 and CD45RO, occasional reactivity for CD43, and lack of other specified markets.

Notes: Lymphoepithelioma-like carcinoma of the skin (LELCS) is a recently-described tumor entity with a microscopic resemblance to undifferentiated carcinoma of the nasopharynx. Only five cases of this lesion have been reported heretofore. We document three additional examples of LELCS that were composed of clustered dermal arrays of cytologically malignant, mitotically active polygonal cells, without connections to the overlying epidermis or skin appendages. Chronic inflammatory cells were interspersed throughout each of the tumors. Two of them demonstrated multiple foci of trichilemmal-type keratinization among the neoplastic cells, whereas the other exhibited focal eccrine ductal or glandular differentiation. None of the neoplasms was found to contain nucleic acid of Epstein-Barr virus by in situ hybridization. It is postulated that LELCS represents a primitive cutaneous appendage tumor. Based on the results of a prior publication and those of the current assessment, this neoplasm is thought to have the potential for both sweat glandular and follicular differentiation.

Notes: In the skin, separation of selected lymphomas from lymphoid hyperplasia can be challenging. The authors examined 45 cutaneous lymphomas, excluding mycosis fungoides (26 small lymphocytic or mixed tumors; 19 large-cell lymphomas), 10 “atypical” lesions, and 40 lesions of presumed lymphoid hyperplasia, comparing morphologic attributes of such proliferations with their immunophenotypes in paraffin sections. The object of this study was to determine whether immunologic data obtained from routinely-processed specimens could be used to further objectify morphologic interpretations. Features favoring lymphonia included a lesional epicenter in the lower clermis or subcutis; poor circumscription of lymphoid aggregates; and dissection of lymphoid cells between collagen bundles. Immunostains included antibodies to CD20, CD43, CD45, CD45RO, CD45RA, CD68, proliferating cell nuclear antigen (PCNA), and MB2. Eleven of 26 small lymphocytic or mixed-cell lymphomas and 3 of 10 “atypical” cases demonstrated an abnormal immunophenotype, including co-expression of CD43 and CD20 or non-physiological CD45RA distribution. In contrast, none of 40 cases with benign features manifested aberrant antigen expression. Thirty-one of 37 cases in which 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:03036987:CUP481:les" location="les.gif"/〉75% of the cells typed as B lymphocytes showed malignant morphologic features, 5 were “atypical” and possibly lymphomatous, and only one had benign features. PCNA stains showed greater positivity of the lymphoid nuclei in Lymphomas, and a labeling index of 〈30% was correlated with malignancy in this context. These observations indicate that immunostaining may provide useful adjunctive information in distinguishing benign from malignant cutaneous lymphoid proliferations in paraffin sections.Ritter JH, Adesokan PN, Fitzgibbons JF, Wick MR. Paraffin section immunohistochemistry as an adjunct to morphologic analysis in the diagnosis of cutaneous lymphoid infiltrates.

Notes: There are many similarities in the morphology of benign and malignant lesions of the sweat glands and the breasts. The recently described cutaneous mammary-like sweat glands, also known as mixed sweal glands or apoeccrine glands, are also a likely source of selected proliferations that closely mimic those of the breast. We present three cases of breast-like lesions arising in the skin that demonstrate the ways in which the morphologic and pathologic continuum of the mammary glands, cutaneous mammary-like glands, and sweat glands can produce difficulties in precise diagnosis. The examples demonstrate that an anatomic location outside the milk line does not preclude the diagnosis of ectopic mammary tissue, and that lesions closely resembling those of the breast may also arise outside the milk line from conventional sweat glands or mixed sweat glands. The concept of homologous lesions of the breast, breast-like glands and sweat glands, in which morphology is partially mirrored by biochemical similarities, provides a perspective for classification of problematic cases of breast-like cutaneous lesions.

Notes: The distinction between squamoid basal cell carcinoma and basaloid squamous cell carcinoma (or between BCC and trichoepithelioma variants) is usually made readily on the basis of defined histological criteria. However, these differential diagnoses occasionally can pose difficult morphological problems. The stated distinctions are clinically important because the risk of progressive disease is significantly higher with squamous carcinoma of the skin than with basal cell carcinoma (BCC), and a trichoepithelioma misinterpreted as BCC burdens the patient with an inaccurate diagnosis that may result in inappropriate surgery. Recent reports have suggested that reactivity with the monoclonal antibody Ber-EP4 is capable of separating histologically similar basal cell and squamous carcinomas, and that ihe expression of bcl-2 or CD34 antigen is able to distingtush BCC from trichoepithelioma. However, corroborative studies of these contentions are few in number. In order to investigate the usefulness of the stated immunostains in the above-cited differential diagnoses, the authors analyzed 45 basal cell carcinomas and 22 squamous carcinomas, as well as 36 trichoepitheliomas. The monoclonal antibodies Ber-EP4, My10 (CD34), and anti-bcl-2 were applied to formalin-fixed paraffin sections in all cases, using a standard avidin-biotin-peroxidase complex method. Most BCCs demonstrated strong, diffuse cytoplasmic labeling with Ber-EP4 and anti-bcl-2. In contrast, the squamous carcinomas were uniformly negative for the former marker and only focally reactive for the latter in four examples. ‘Peripheral’bcl-2 staining of trichoepitheliomas was noted in 24 of 33 of the immunoreactive tumors, but the remainder were marked diffusely and similarly to most BCCs. Among the latter, immature trichoepitheliomas were diffusely reactive for this marker in 6 of 8 cases. Labeling of epithelium for CD34 failed to discriminate between any of the tumor types under evaluation, whereas staining of peritumoral stroma was characteristic of the majority of trichoepitheliomas and more than one-third of metatypical basal cell carcinomas. These data support the suggestion that Ber-EP4 and bcl-2 are useful in the separation of BCC from squamous carcinomas. Nevertheless, they also serve to caution against reliance upon bcl-2 and CD34 immunostains in attempting to distinguish BCC from trichoepithelioma in histologically enigmatic cases. There is currently no certain method other han conventional microscopy that can be applied successfully to the latter problem.

Notes: It is important to identify T1-substage breast carcinomas (BCs) which are inherently aggressive, so that these can be managed more assertively. The purpose of this study was to distinguish those T1 BCs with the potential to metastasize to axillary lymph nodes from those lacking that ability by multiparametric analysis of several clinicopathologic features. The authors studied 197 patients with invasive BC who had undergone modified radical mastectomy; 161 tumors were ductal and 26 were lobular BCs. The study group was stratified by age into two groups: ≤34 years (n = 34) and 35–84 years (n = 153). Pathologic lymph node status was correlated with estrogen receptor (ER) and progesterone receptor (PR) tumor positivity, MIB-1 proliferation index, and immunoreactivity for mutant p53 protein. These factors were studied immunohistologically using standard methodology and microwave-mediated epitope retrieval. Statistical analyses employed accepted techniques. Women in this study ranged from 22 to 84 years of age; 39 (21%) had positive lymph nodes. ER-positive tumors comprised 73% of the total; similarly, 65% were PR positive. The MIB-1 index was greater than 10% in 44% of lesions, and 14% demonstrated labeling for mutant p53 protein. Using crude odds ratio data, the MIB-1 index was the only indicator found to predict lymph node metastasis significantly (p 〈 0.001). Moreover, even when adjustments were made for patient age, logistic regression analysis confirmed the utility of MIB-1-values of greater than 10% in this context, with a 4.4 greater likelihood of metastasis (p 〈 0.001). MIB-1 indices of greater than 10% are associated with a risk of lymph node metastasis from T1 BCs, independent of patient age. Hormone receptor status and immunohistologic p53 status are not predictors of nodal involvement in this specific setting.

Notes: “Adenoma sebaceum of Pringle” (ASP) is a misnomer. The tumor is not an adenoma and is not derived from sebaceous glands. The lesion is characterized by dermal fibrosis and associated vascular proliferation and dilatation. Changes in contiguous sebaceous glands and other adnexal structures are merely secondary. Thus, “angiofibroma” would be a more appropriate name. The histologic changes in ASP (and in related pathologic lesions) suggest that it is a hamartoma rather than a true neoplasm. However, the embryologic tissue of its origin is not definitively known.

Notes: Six solitary, dermal or subcutaneous lesions occurring in adult patients are presented. These masses had a circumscribed, lobulated configuration; they were composed of fusiform and epithelioid cells that lacked atypical nuclear features. The pattern of growth featured fascicles and nests, a myxofibrous stroma, and prominent blood vessels with a focally “hemangiopericytoid” appearance. Immunohistochemical analyses showed uniform reactivity for vimentin and alpha isoform-actin, with negativity for desmin and neural determinants. The overall appearance of the lesions was similar to that of “infantile myofibromastosis,” and corresponded to previous descriptions of “solitary myofibroma(tosis)” in adults. Immunophenotypic and ultra-structural support exists for a proposed myofibroblastic nature for such proliferations. Differential diagnostic considerations include neurothekeomas, plexiform fibrous histiocytomas, nodular fasciitis, cutaneous inflammatory pseudotumors, dermatomyofibromas, leiomyomas, and other forms of fibromatosis affecting the skin and superficial soft tissues.