Marcelo G. Horenstein

Desmoplastic (sclerotic) nevus: an underrecognized entity that resembles dermatofibroma and desmoplastic melanoma.

Desmoplastic (sclerotic) nevus, a benign melanocytic neoplasm characterized by predominantly spindle-shaped nevus cells within a fibrotic stroma, can be confused with fibrous lesions and other melanocytic proliferations, including desmoplastic melanoma. We compared the histologic and immunohistochemical features of 16 desmoplastic nevi, nine desmoplastic melanomas, four hypopigmented blue nevi, and six dermatofibromas. The similarities between desmoplastic nevi and dermatofibromas included epidermal hyperplasia (12 of 16), presence of keloidal collagen (15 of 16), hypercellularity (16 of 16), and increased numbers of factor XIIIa-positive dendritic cells (12 of 12). The absence of adnexal induction (0 of 16), the rarity of lesions with multinucleated cells (3 of 16) or epidermal hyperpigmentation (2 of 16), and the presence of S-100 immunoreactivity (16 of 16) and melanocytic proliferation (9 of 16) helped differentiate desmoplastic nevi from dermatofibromas. The similarities between desmoplastic nevi and desmoplastic melanomas included the presence of atypical cells (16 of 16) and HMB-45 expression in the superficial portion of the lesions (11 of 16). The infrequent location on the head or neck (1 of 16), the absence of mitotic figures (0 of 16), a significantly lower number of Ki-67-reactive cells, and a decrease in HMB-45 expression in the deep area of the lesions (8 of 11) helped distinguish desmoplastic nevi from desmoplastic melanoma. Desmoplastic nevi had overlapping features with hypopigmented blue nevi, but features tending to favor the latter included a predominance of ovoid nuclei, higher numbers of atypical cells, and homogeneous staining with HMB-45. We conclude that a combination of histologic and immunohistochemical criteria facilitates the reliable diagnosis of desmoplastic nevus from its simulators.

CD30-positive atypical lymphoid cells in common non-neoplastic cutaneous infiltrates rich in neutrophils and eosinophils.

CD30-positive cells characterize lymphomatoid papulosis and anaplastic large cell lymphoma but can also be found in nonneoplastic skin disorders. Purportedly, CD30 is useful in the differential diagnosis between insect bites and lymphomatoid papulosis. Recently, a subtype of neutrophil-rich CD30-positive anaplastic large cell lymphoma has been described, which may enter the differential diagnosis of cutaneous neutrophil-rich inflammatory infiltrates. We studied atypical CD30-positive lymphoid cells in five eosinophil-rich and 23 neutrophil-rich common nonneoplastic skin infiltrates. The eosinophil-rich cases included five insect bites. The neutrophil-rich cases included 9 inflammatory (hidradenitis suppurativa [n = 4], stasis ulcer [n = 2], ruptured cyst, rhynophyma, and Sweet syndrome); 12 infectious (bacterial [n = 8], viral [n = 2] and fungal [n = 2] etiologies); and 2 environmental (spider bites) cases. Atypical CD30-positive cells were found in 4 of 5 eosinophil-rich, 8 of 9 neutrophil-rich inflammatory, 6 of 12 neutrophil-rich infectious, and 2 of 2 neutrophil-rich environmental cases. Polymerase chain reaction analysis for B- and T-cell clonality and cell counts of neutrophils, eosinophils, plasma cells, B cells (using CD20), and T cells (using CD3) were performed in the cases that contained atypical CD30-positive lymphoid cells. CD30-positive cells averaged 4.8% of the cells counted in the areas where they were most concentrated. Of the 18 cases that amplified with polymerase chain reaction, all were polyclonal for T-cell receptor rearrangements; 10 were polyclonal and 8 oligoclonal for B-cell immunoglobulin rearrangements. There was no correlation between B-cell oligoclonality with CD30-positive cell counts, a particular disease, or a disease category. In conclusion, the presence of CD30-positive atypical lymphoid cells in 71.4% of the common nonneoplastic cases studied, even in the presence of clonal B-cell populations, warrants caution in the interpretation of these cells as malignant, particularly when dealing with the differential diagnosis of lymphomatoid papulosis or neutrophil-rich anaplastic large cell lymphoma.

Presacral carcinoid tumors: report of three cases and review of the literature.

The clinical, microscopic, immunohistochemical, and ultrastructural features of three carcinoid tumors of the presacral region are reviewed. All tumors occurred in young women and did not involve the rectum. The predominant microscopic pattern was trabecular. The differential diagnosis included paraganglioma and myxopapillary ependymoma. Immunohistochemically, neuroendocrine markers and low molecular weight cytokeratins were expressed in all cases. Neurosecretory granules were identified in the single case studied by electron microscopy. One case was associated with a tailgut cyst (retrorectal cystic hamartoma). Two patients were treated with complete local excision and are free of disease 3 and 4 years after surgery. One case metastasized to both breasts and recurred locally after an incomplete excision. This report expands the already long list of sites where carcinoid tumors can arise. The frequent association of these tumors with tailgut cysts and their histologic similarities to rectal carcinoid tumors suggest that the most likely derivation of presacral carcinoid tumors is from hindgut rests.

Dysplastic naevi with moderate to severe histological dysplasia : a risk factor for melanoma

Background  The risk of malignant melanoma associated with histologically dysplastic naevi (HDN) has not been defined. While clinically atypical naevi appear to confer an independent risk of melanoma, no study has evaluated the extent to which HDN are predictive of melanoma.

Indeterminate fibrohistiocytic lesions of the skin : is there a spectrum between dermatofibroma and dermatofibrosarcoma protuberans?

Routine histology and immunohistochemistry can usually distinguish dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP). DF generally expresses factor XIIIa whereas DFSP generally expresses CD34. The authors report 10 cutaneous fibrohistiocytic lesions combining clinical, histologic, and immunohistochemical features of both DF and DFSP. The lesions had an average size of 1.2 cm (range, 0.4-2.7 cm), and occurred on the trunk (n = 6), extremities (n = 3), and face (n = 1) of four men and six women (average age, 30.6 yrs; age range, 15-50 yrs). Eight lesions exhibited acanthosis and densely cellular fascicles with focal storiform areas. All had keloidal collagen, infiltrated the subcutis in a honeycomb pattern, and had low mitotic counts (0 to 4 mitoses per square millimeter). All were diffusely immunoreactive for factor XIIIa (30%-60% of the neoplastic cells) as well as CD34 (20%-70%). This series raises the possibility of a biologic spectrum between DF and DFSP; however, double-immunolabeling studies showed no notable coexpression of factor XIIIa and CD34 by individual cells, suggesting coexistence of two different cellular populations. After an average follow up of 22.3 months (range, 10-46 mos) in six cases, a single recurrence was documented. The ambiguous histologic features and the potential for local recurrence suggest that performing a complete excision may be prudent in these diagnostically indeterminate lesions.

Nuchal-type fibroma in two related patients with Gardner's syndrome

Nuchal-type fibroma is a distinct subcutaneous and dermal fibrous tissue proliferation that has been previously definitely identified in one patient with Gardners syndrome and has been possibly present in two others. Gardners syndrome is an autosomal-dominant condition with variable expressivity that comprises epidermoid cysts, fibrous tumors, osteomas, intestinal polyposis, as well as other findings. We report two cases of nuchal-type fibroma presenting in a 13-year-old boy in the right upper back and in his 60-year-old grandfather in the upper chest at the posterior axillary line. Both individuals carried a diagnosis of Gardners syndrome and neither of them had diabetes. Although the boy has as of now only presented with cutaneous manifestations of Gardners syndrome, his grandfather has exhibited both cutaneous and intestinal evidence of this syndrome. In addition, the boys mother and her sister have documented Gardners syndrome. Light microscopic findings of nuchal-type fibroma from both patients include paucicellular, haphazardly arranged collagen bundles with entrapped adipose tissue. A marked diminution of elastic fibers was noted with Van-Gieson stains. The lesions were diffusely positive for CD34 and contained a few factor XIIIa-positive cells. Electron microscopic analysis revealed no differences between the collagen comprising the nuchal-type fibroma as compared with control dermal collagen obtained from skin away from the tumor. These cases strengthen the view that there is an association between nuchal-type fibroma and Gardners syndrome.

The pathobiology of Kaposi’s sarcoma: advances since the onset of the AIDS epidemic

Since the perplexing early Kaposi’s sarcoma (KS) observations at the dawn of the acquired immunodeficiency syndrome epidemic, KS has been extensively studied, revealing a complex disease. The identification and complete elucidation of the genome of its causal agent, the KS‐associated herpesvirus/human herpesvirus 8, have shed important insights into the pathobiology of this disease. The purpose of this review is to describe the scientific advances and understanding of KS over the past three decades.

Quantitation of intraepidermal T-cell subsets in formalin-fixed, paraffin-embedded tissue helps in the diagnosis of mycosis fungoides

Differentiation between mycosis fungoides (MF) and cutaneous inflammatory processes can usually be made on clinical and histologic grounds. In difficult cases, immunohistochemical studies can he helpful since MF infiltrates usually contain a predominance of CD4+ lymphocytes, while most inflammatory lesions usually have a mixture of CD4+ and CD84‐ lymphocytes. However, this determination has traditionally required the use of frozen tissue, thus severely limiting its usefulness. Recently, antibodies that differentially label CD4+ and CD8+ lymphocytes in formalin‐fixed, paraffin‐embedded tissue have become available (OPD4 and C8/144B respectively. DAKO (Carpinteria, CA, USA). This study tests the utility of these antibodies in the pathologic diagnosis of MF and inflammatory lesions with significant exocytosis. In 9 cases of MF for which both frozen and fixed tissues were available for comparison, the OPD4+ cell count in fixed tissue was significantly lower than the Leu‐3a+ cell count in frozen tissue. Also, the C8/144B+ cell count in fixed tissue was higher than the Leu‐2a+ cell count in frozen tissue, although this difference was not significant statistically. In a larger series for which only fixed tissue was available, epidermal CD4:CD8 ratios were significantly greater in 23 MF cases (mean 4.0±4.76) than in 35 inflammatory cases (mean 0.6±0.42; p = 0.001). Thus, although the studied antibodies appear to detect different epitopes in frozen versus paraffin‐embedded tissue, demonstration of an elevated CD4:CD8 ratio in fixed tissue supports the diagnosis of MF, and is a helpful adjunct to routine histopathology.

Primary chondroid melanoma

Background: Malignant melanoma is notorious for the wide range of histologic patterns it can assume, among the least frequent of which is chondroid melamona.

Investigation of the hair follicle inner root sheath in scarring and non-scarring alopecia

Background:  Premature desquamation of the inner root sheath (IRS) is described as a defining histologic feature of follicular degeneration syndrome/central centrifugal cicatricial alopecia (CCCA). However, IRS abnormalities have been noted in other types of alopecia.