Aberrant Melan-A expression in atypical fibroxanthoma and undifferentiated pleomorphic sarcoma of the skin.

BACKGROUND: Atypical fibroxanthoma (AFX) is a distinctive clinicopathologic entity presenting on sun-damaged skin of the elderly. Its behavior is benign if strict diagnostic criteria are applied. Tumors showing invasion of deeper structures or perineural/lymphovascular invasion are best regarded as undifferentiated pleomorphic sarcoma of the skin. The diagnosis requires immunohistochemical studies to exclude melanoma, squamous cell carcinoma, angiosarcoma and leiomyosarcoma. METHODS: Two AFX and one undifferentiated pleomorphic sarcoma showing aberrant expression of Melan-A were identified. Clinical data were obtained and histopathological features, immunohistochemical profile and electron microscopy were assessed. RESULTS: All tumors arose on sun-damaged skin of elderly males. Two AFX showed pushing growth into superficial subcutis only. The undifferentiated pleomorphic sarcoma was characterized by infiltrative growth into galea as well as perineural invasion. Multifocal expression of Melan-A and MART-1 was largely limited to tumor giant cells in the absence of S100 or HMB-45 labeling. No melanosomes or premelanosomes were identified by electron microscopy. CONCLUSIONS: Aberrant expression of Melan-A and MART-1 in AFX and undifferentiated pleomorphic sarcoma of the skin represents an important diagnostic pitfall with potential for misdiagnosis as melanoma.

Immune phenotype predicts risk for posttransplantation squamous cell carcinoma.

Cutaneous squamous cell cancer (SCC) affects up to 30% of kidney transplant recipients (KTRs) within 10 years of transplantation. There are no reliable clinical tests that predict those who will develop multiple skin cancers. High numbers of regulatory T cells associate with poor prognosis for patients with cancer in the general population, suggesting their potential as a predictive marker of cutaneous SCC in KTRs. We matched KTRs with (n = 65) and without (n = 51) cutaneous SCC for gender, age, and duration of immunosuppression and assessed several risk factors for incident SCC during a median follow-up of 340 days. Greater than 35 peripheral FOXP3(+)CD4(+)CD127(low) regulatory T cells/microl, <100 natural killer cells/microl, and previous SCC each significantly associated with increased risk for new cutaneous SCC development (hazard ratio [HR] 2.48 [95% confidence interval (CI) 1.04 to 5.98], HR 5.6 [95% CI 1.31 to 24], and HR 1.33 [95% CI 1.15 to 1.53], respectively). In addition, the ratio of CD8/FOXP3 expression was significantly lower in cutaneous SCC excised from KTRs (n = 25) compared with matched SCC from non-KTRs (n = 25) and associated with development of new cutaneous SCCs. In summary, monitoring components of the immune system can predict development of cutaneous SCC among KTRs.

Tumid lupus erythematosus occurring following highly active antiretroviral therapy for HIV infection: a manifestation of immune restoration.

Tumid lupus erythematosus (LE) is a relatively rare and only recently recognized subset of chronic cutaneous lupus. We report a case occurring in a male with HIV infection whereby his rash was only unmasked by immune restoration following highly active antiretroviral therapy (HAART). The phenomenon of latent inflammatory or autoimmune disease appearing following HAART is now recognized as the "immune restoration syndrome" and tumid LE has not been reported in this setting previously. Fortunately this variant of lupus does not result in scarring and is responsive to anti-malarials, allowing continuation of HAART in this patient.

Skin cancers of the hand: a series of 541 malignancies.

BACKGROUND: Skin cancers of the hand are uncommon and poorly documented. The objective of this study was to review a large cohort of patients with hand skin malignancies to determine tumor characteristics, management techniques, and outcomes. METHODS: A retrospective review of consecutive patients with surgically excised primary cutaneous hand malignancies at the John Radcliffe Hospital between 1993 and 2010 was performed. Records were reviewed to determine tumor characteristics, demographics, and management details. Outcome parameters included margins and completeness of excision, recurrence, metastatic spread, and survival. RESULTS: A total of 407 patients (65.8 percent male; mean age, 72.2 ± 0.7 yr) presented with 541 primary cutaneous hand malignancies and were followed up for a mean period of 24 months. Half the cohort had previous skin cancers and almost one in five developed further hand skin cancers. Squamous cell carcinoma comprised 78.0 percent, basal cell carcinoma 11.3 percent, and melanoma 3.9 percent of cases. Incidence was highest on the dorsum of the hand. Surgical margins were proportionate to tumor size, and most defects required soft-tissue reconstruction. Recurrence was uncommon in melanoma and rare in squamous and basal cell carcinomas. Lymph node metastasis and death were rare in patients with squamous cell carcinoma but relatively common in those with melanoma. CONCLUSIONS: Squamous cell carcinomas are the most common skin malignancy of the hand, frequently require soft-tissue reconstruction, and those occurring in the web spaces or on the dorsum of the proximal phalanges are more sinister malignancies with a greater propensity for metastatic spread. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Novel markers of normal and neoplastic human plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) are involved in innate immunity (eg, by secreting interferons) and also give rise to CD4+CD56+ hematodermic neoplasms. We report extensive characterization of human pDCs in routine tissue samples, documenting the expression of 19 immunohistologic markers, including signaling molecules (eg, BLNK), transcription factors (eg, ICSBP/IRF8 and PU.1), and Toll-like receptors (TLR7, TLR9). Many of these molecules are expressed in other cell types (principally B cells), but the adaptor protein CD2AP was essentially restricted to pDCs, and is therefore a novel immunohistologic marker for use in tissue biopsies. We found little evidence for activation-associated morphologic or phenotypic changes in conditions where pDCs are greatly increased (eg, Kikuchi disease). Most of the molecules were retained in the majority of pDC neoplasms, and 3 (BCL11A, CD2AP, and ICSBP/IRF8) were also commonly negative in leukemia cutis (acute myeloid leukemia in the skin), a tumor that may mimic pDC neoplasia. In summary, we have documented a range of molecules (notably those associated with B cells) expressed by pDCs in tissues and peripheral blood (where pDCs were detectable in cytospins at a frequency of <1% of mononuclear cells) and also defined potential new markers (in particular CD2AP) for the diagnosis of pDC tumors.

Mitotic count is not predictive of clinical behavior in hidradenoma papilliferum of the vulva: a clinicopathologic study of 19 cases.

Although it is generally recognized that some benign sweat gland neoplasms may show appreciable mitotic activity, there are few reports of its quantitative analysis in specific tumor types or of its correlation with clinical behavior. The presence of a large number of mitoses in a sweat gland tumor for which the histologic criteria of malignancy are not well defined, particularly in association with nuclear abnormalities, may produce a considerable diagnostic challenge. We recently encountered such a problem in a putative case of hidradenoma papilliferum. Therefore, we have undertaken a retrospective clinicopathologic study of 19 cases originally diagnosed as hidradenoma papilliferum or probable hidradenoma papilliferum, with a particular emphasis on the relationship of the mitotic index to clinical behavior. The age range of the cases was 41 to 92 years (mean 56.8 years). In all cases in which the margins could be evaluated, the tumors were well circumscribed (15/15), but in 4 cases circumscription could not be assessed because the specimen was fragmented. All showed focal mild nuclear pleomorphism. Mitoses were present in both epithelial and myoepithelial cells. The mitotic index varied from 0 to 5.3 mitoses/mm2 (0 to 13 mitoses per 10 high power fields (hpf); 1 hpf=0.246 mm2), with a mean of 2.4/mm2 (6/10 hpf) and a median of 0.8/mm2 (2/10 hpf). No atypical mitoses were identified. The proliferative fraction (MIB-1 index) correlated with the mitotic index (correlation coefficient 0.94; P<0.0001) and varied from 1% to 10.5% (mean 3.9%, median 3.0%). There were no recurrences or metastases over a mean period of 8 years. Consequently, we have shown that the mitotic index in these lesions can be variable and often high, but it does not predict a more aggressive outcome.

Atrophic dermatofibrosarcoma protuberans.

A 48-year-old woman presented with a 20-year history of an asymptomatic depressed atrophic plaque on the abdomen. Five years earlier a punch biopsy of the same lesion had been carried out and a diagnosis of dermatofibroma was made. She was reassured and discharged. Further consultation was sought due to extension and thickening of the lesion. Re-examination of the initial and new incisional biopsy specimens, along with histochemical staining for CD34, established the diagnosis of atrophic dermatofibrosarcoma protuberans. A wide local excision was carried out. There has been no recurrence at 9 months of follow up.

Treatment of nevoid hyperkeratosis of the nipple and areola by shave excision.

The case is presented of a 29-year-old female who, at the age of 13 years, developed bilateral verrucous thickening of her areolae. Despite the condition causing her significant psychosocial morbidity, a specialist referral was initially denied on the grounds that no treatment was apparently available. The condition progressively deteriorated over the subsequent 14 years. She was eventually referred for a dermatology opinion, and the diagnosis of nevoid hyperkeratosis was made. Topical therapy with keratolytics was unsuccessful, and she was referred for a plastic surgery review. Bilateral shave excision of the lesion was performed under general anesthesia, with a satisfactory outcome and no evidence of recurrence at 10 months.