A Pigmented Subcutaneous Nodule on the Scalp.

A 52-year-old man presented to his primary doctor with a slow-growing cystic lesion on his occipital scalp. His primary care doctor diagnosed the lesion as a pilar cyst and recommended observation because the lesion was asymptomatic at that time. The patient had no significant medical or surgical history. There was no family history of skin cancer or other malignancies.

Seasonal variations in dermatologic and dermatopathologic diagnoses: a retrospective 15-year analysis of dermatopathologic data.

BACKGROUND: Certain dermatologic conditions are known to show seasonal variations in frequency, the reasons for which are unclear but in some cases may be attributable to changes in ambient weather conditions. OBJECTIVES: The current study was conducted to determine whether seasonal trends might exist for dermatologic conditions including erythema multiforme, guttate psoriasis, erythema dyschromicum perstans (ashy dermatosis), pityriasis lichenoides, and pityriasis rosea. METHODS: Data were derived from a 15-year retrospective review of electronic records from a large dermatopathology laboratory located in the mid-Atlantic region of the USA. Numbers of diagnoses per month and "per season" were determined. Pairwise comparisons of seasonal data were made using two-sample t-tests with significance set at P ≤ 0.05. RESULTS: Perniosis (chilblains) was significantly more common in winter and spring (P = 0.001). Hand, foot, and mouth disease was statistically more prevalent in summer and autumn (P = 0.028). Erythema multiforme was most common in spring and summer (P = 0.004). Grover's disease was most common in winter and spring (P = 0.000039). Guttate psoriasis was non-significantly more common in winter and spring (P = 0.076). No statistically significant seasonal variation was found for erythema dyschromicum perstans (P = 0.899), pityriasis rosea (P = 0.727), or pityriasis lichenoides (P = 0.366). CONCLUSIONS: This study found statistically significant seasonal trends for several dermatologic conditions. The study was primarily epidemiologic and was not intended to address histopathologic differences that might underlie the seasonal variations observed. However, further investigation of seasonal differences in the histopathology of erythema multiforme may prove interesting.

Dermatologic presentations of orthopedic pathologies: a review of diagnosis and treatment.

Dermatologic presentations of orthopedic diseases are commonly encountered in the dermatology clinic. These disorders often necessitate prompt recognition in order to properly refer for definitive treatment as well as to avoid unnecessary diagnostic procedures. As such, the presentations of these diseases as well as the treatments available deserve special attention. This review aims to identify orthopedic diseases with dermatologic presentations and discuss the diagnosis and treatment of these pathologies. In conducting this review, a comprehensive literature search was conducted. Our inquiry was limited to conditions with a unitary orthopedic etiology. By excluding syndromic dysfunctions with both orthopedic and dermatologic manifestations, we were able to create a consistent approach to the review. At the same time, such exclusions created an omission of many important disease processes that require the cooperation of orthopedists and dermatologists. In all, 19 orthopedic disorders and disorder classes with dermatologic findings were identified and carefully examined. The orthopedic pathologies identified require varying diagnostic and therapeutic approaches. While some do not warrant further work-up or referral, the disease course of certain pathologies is drastically altered by timely recognition, cautious diagnostic interrogation, and prompt referral.

Increasing incidence of lentigo maligna melanoma subtypes: northern California and national trends 1990-2000.

Worldwide, lentigo maligna melanoma (LMM) comprises 4%-15% of cutaneous melanoma and occurs less commonly than superficial spreading or nodular subtypes. We assessed the incidence of melanoma subtypes in regional and national Surveillance, Epidemiology, and End Results (SEER) cancer registry data from 1990 to 2000. Because 30%-50% of SEER data were not classified by histogenetic type, we compared the observed SEER trends with an age-matched population of 1024 cases from Stanford University Medical Center (SUMC) (1995-2000). SEER data revealed lentigo maligna (LM) as the most prevalent in situ subtype (79%-83%), and that LMM has been increasing at a higher rate compared with other subtypes and to all invasive melanoma combined for patients aged 45-64 and > or =65 y. The SUMC data demonstrated LM and LMM as the only subtypes increasing in incidence over the study period. In both groups, LM comprised > or =75% of in situ melanoma and LMM > or =27% of invasive melanoma in men 65 y and older. Regional and national SEER data suggest an increasing incidence of LM and LMM, particularly in men > or =age 65. An increased incidence of LM subtypes should direct melanoma screening to heavily sun-exposed sites, where these subtypes predominate.

High-resolution array-based comparative genomic hybridization for distinguishing paraffin-embedded Spitz nevi and melanomas.

Distinguishing between Spitz nevus and melanoma presents a challenging task for clinicians and pathologists. Most of these lesions are submitted entirely in formalin for histologic analysis by conventional hematoxylin and eosin-stained sections, and fresh-frozen material for ancillary studies is rarely collected. Molecular techniques, such as comparative genomic hybridization (CGH), can detect chromosomal alterations in tumor DNA that differ between these 2 lesions. This study investigated the ability of high-resolution array-based CGH to serve as a diagnostic test in distinguishing Spitz nevus and melanoma using DNA isolated from formalin-fixed and paraffin-embedded samples. Two of 3 Spitz nevi exhibited no significant chromosomal alterations, while the third showed gain of the short arm of chromosome 11p. The latter finding has previously been described as characteristic of a subset of Spitz nevi. The 2 melanomas showed multiple copy number alterations characteristic of melanoma such as 1q amplification and chromosome 9 deletion. This study has shown the utility of array-based CGH as a potential molecular test in distinguishing Spitz nevus from melanoma. The assay is capable of using archival paraffin-embedded, formalin-fixed material; is technically easier to perform as compared with conventional CGH; is more sensitive than conventional CGH in being able to detect focal alterations; and can detect copy number alterations even with relatively small amounts of lesional tissue as is typical of many skin tumors.

Primary dermal melanoma: a distinct subtype of melanoma.

BACKGROUND: The term primary dermal melanoma has been used to describe a subtype of melanoma confined to the dermis and/or subcutaneous fat that histologically simulates metastasis but is associated with an unexpectedly prolonged survival. We report 7 cases of primary dermal melanoma diagnosed from 1998 to 2002 with no identifiable junctional or epidermal component or nevoid precursor. Histopathologic and immunohistochemical features were compared with known cases of cutaneous metastasis and nodular melanoma in an attempt to differentiate this entity from clinical and pathologic mimics. OBSERVATIONS: Seven patients had a single dermal and/or subcutaneous focus of melanoma. Metastatic staging workup findings were negative, including results from sentinel node and imaging studies. Mean Breslow depth was 7.0 mm, and mean maximum tumor diameter was 6.2 mm. The study cohort showed 100% survival at mean follow-up of 41 months (range, 10-64 months). Immunohistochemical analysis with S100, HMB-45, Ki-67, CD34, and p75 antibodies showed no significant staining patterns compared with metastatic and nodular melanomas. CONCLUSIONS: Primary dermal melanoma appears to be a distinct subtype of melanoma based on the excellent prognosis associated with this case series and others. Additional research focusing on cause, appropriate staging, and outcome of previously identified solitary dermal metastasis is warranted to further delineate this entity.

CD30+ cutaneous lymphoproliferative disorders: the Stanford experience in lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma.

BACKGROUND: CD30+ cutaneous lymphoproliferative disorders (CLPDs) include lymphomatoid papulosis, borderline cases of CD30+CLPDs, and primary cutaneous anaplastic large cell lymphoma (PCALCL). Prior studies have shown CD30+CLPDs have an excellent prognosis. OBJECTIVE: We sought to present the single-center experience of Stanford University, Stanford, Calif, in the management of CD30+CLPDs. METHODS: A retrospective cohort analysis of 56 patients with CD30+CLPDs treated at our institution was performed. RESULTS: No patients with lymphomatoid papulosis died of disease, and overall survival was 92% at 5 and 10 years. Disease-specific survivals at 5 and 10 years for PCALCL were 85%. Disease-specific survival at 5 years for localized versus generalized PCALCL was 91% versus 50% (P =.31). PCALCL was highly responsive to treatment, but the relapse rate was 42%. In all, 3 patients progressed to extracutaneous stage of disease. No clinical or histologic factors analyzed were predictive of worse outcome in lymphomatoid papulosis and PCALCL. CONCLUSION: Similar to prior reports from multicenter European groups, the single-center experience at our institution demonstrates CD30+CLPDs have an overall excellent prognosis; however, cases of PCALCL with poor outcome do exist.

Expression of the B-cell proliferation marker MUM1 by melanocytic lesions and comparison with S100, gp100 (HMB45), and MelanA.

The diagnosis of malignant melanoma remains one of the most difficult to render in surgical pathology, partially because of its extreme histologic variability. Limits in the sensitivity and/or specificity of the currently available melanocytic markers such as anti-S100, HMB45, and anti-MelanA further complicate this problem. Previous work has demonstrated that the B-cell proliferation/differentiation marker MUM1/IRF4 is detected in malignant melanoma and hematolymphoid malignancies, but not in any other neoplasm tested (including colonic, lung, breast, and ovarian carcinomas). In the current study, we have examined MUM1 protein expression in 61 melanocytic lesions and compared the diagnostic usefulness of this marker with that of anti-S100, HMB45, and anti-MelanA. The results indicate that MUM1 is positive in 33/36 (92%) cases of melanoma (21/22 [95%] conventional primary melanomas and 12/14 [86%] metastatic melanomas). In comparison, positivity was seen with anti-S100 in 36/36 cases (100%, 22 primary and 14 metastatic), HMB45 in 28 cases (78%, 17 primary and 11 metastatic), and anti-MelanA in 27 cases (75%, 19 primary and 8 metastatic). Although negative in schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors, MUM1 is detected in only one in eight cases of spindle cell and desmoplastic melanomas. With the exception of desmoplastic and spindle cell melanomas, MUM1 appears to be a sensitive and specific immunohistochemical stain for melanocytic lesions and may prove to be a useful addition to the current panel of melanoma markers.

Intraparenchymal nevus cell aggregates in lymph nodes: a possible diagnostic pitfall with malignant melanoma and carcinoma.

It is well documented that nevus cells can be found within the fibrous capsule and trabeculae of lymph nodes; however, it is less well known that nevus cells can also be found in the lymph node parenchyma. We report the findings in 13 cases of nevus cell aggregates located within the cortical and/or medullary parenchyma of lymph nodes. Seven of the 13 patients had a primary diagnosis of melanoma, three had no known malignancy, one had breast carcinoma, one had adnexal carcinoma of the skin, and one had squamous cell carcinoma of the tonsil. Of the seven patients with melanoma, four had axillary lymph node dissections and three had inguinal lymph node dissections. The patient with adnexal carcinoma had metastatic carcinoma in 14 of 20 lymph nodes that had been dissected; one of them also had intraparenchymal nevus cells. The patient with squamous cell carcinoma of the tonsil had an intraparenchymal nevus cell aggregate in one of the 21 dissected lymph nodes; all 21 were negative for carcinoma. Nests of intraparenchymal nevus cells ranged from clusters of only a few cells up to 2.1-mm aggregates. No mitotic figures, prominent nucleoli, or lymphatic-vascular invasion were detected in any of the melanocytic aggregates. The melanocytic cells of the nevus cell aggregates expressed S-100 protein and/or MART-1 but not gp100 protein (HMB-45). Less than 1% of the nevus cells expressed Ki-67. The purpose of this study was to draw attention to the finding of nevus cells in the parenchyma of lymph nodes and to alert pathologists to this as a potential diagnostic pitfall, especially in patients with concurrent melanoma or carcinoma. Awareness that nevus cells can be present in nodal parenchyma, analysis of their morphologic features (including comparison with any previous or existing melanoma or carcinoma), and immunophenotyping will help pathologists to establish the correct diagnosis in most instances.

An immunohistochemical study of CD4, CD8, TIA-1 and CD56 subsets in inflammatory skin disease.

BACKGROUND: Antibodies to CD4, CD8, TIA-1, and CD56 are available which perform well in formalin-fixed and paraffin-embedded tissue. While previous studies have investigated CD4 and CD8 subsets in inflammatory skin disease, few have specifically addressed TIA-1 and CD56 reactivity in benign dermatoses. Given that CD8, TIA-1, and CD56 are linked to aggressive lymphoproliferative disorders (i.e. subcutaneous panniculitic T-cell lymphoma, natural killer (NK), and NK/T-cell lymphomas), it would be important to determine their specificity for cutaneous hematologic malignancies. This investigation was undertaken to determine the frequency with which common, benign dermatoses express these four markers. We also sought to determine whether the ratio of CD4- to CD8-positive cells could be used to distinguish among the dermatoses, especially the superficial and deep perivascular ones. METHODS: Formalin-fixed and paraffin-embedded sections from a variety of common inflammatory dermatoses were stained with antibodies to CD4, CD8, TIA-1, and CD56. Positive reactions were scored as a percentage of the entire mononuclear cell infiltrate. RESULTS: All of the dermatoses represented in the study showed TIA-1- and CD56-positive lymphocyte subpopulations. On a case-by-case basis, the percentage of positive cells varied, and while all cases were positive for TIA-1, many were completely negative for CD56. For TIA-1, the percentage of positive cells ranged from 21 to 59%, and for CD56, from < 1 to 9%. The CD4:CD8 ratio ranged from 1.0 to 6.0 but was never less than 1.0. In addition to lymphocytes, TIA-1 also stained polymorphonuclear leukocytes, eosinophils, and mast cells. CONCLUSION: TIA-1- and CD56-positive lymphocytes are common participants in routine inflammatory dermatoses, and therefore these markers are not specific for aggressive lymphoproliferative disorders. Using only immunohistochemical data, the ratio of CD4- to CD8-positive lymphocytes could not be used reliably to separate the superficial and deep perivascular dermatoses from one another. Finally, mast cells are positive for TIA-1 and are commonly seen in normal and inflamed skin, and thus TIA-1 is not specific for cytotoxic T lymphocytes.

Multiple spindle cell lipomas and dermatofibrosarcoma protuberans within a single patient: evidence for a common neoplastic process of interstitial dendritic cells?

This case report describes a 48-year-old man with multiple spindle cell lipomas of the neck and a dermatofibrosarcoma protuberans (DFSP) with fibrosarcomatous transformation of the chest. The presence of familial and nonfamilial multiple spindle cell lipomas within a single patient is a rare event, with only two reports in the current literature. This case represents the first report of multiple spindle cell lipomas occurring in association with a DFSP. It is of particular interest in that both spindle cell lipoma and DFSP represent, at least in part, neoplastic proliferations of CD34(+) spindled cells. The exact nature and differentiation of these spindled cells remains controversial, but prior studies have suggested that they could represent neoplastic interstitial dendritic cells. The association of DFSP and spindle cell lipoma within this single patient suggests that these two tumors (and their histologic variants) may well be linked, conceptually, as neoplastic proliferations of CD34(+) interstitial dendritic cells.

Persistent (recurrent) Spitz nevi: a histopathologic, immunohistochemical, and molecular pathologic study of 22 cases.

This report describes 22 Spitz nevi that seemed to have been clinically removed but persisted and clinically recurred at the biopsy site. These were evaluated in terms of histopathology, immunohistochemistry, and molecular pathology using comparative genomic hybridization (CGH) and fluorescent in situ hybridization. One of these 22 lesions was originally reported as an atypical melanocytic proliferation with some features of a Spitz nevus and was included in the study set at an early stage but was later recognized as melanoma after metastasis to regional lymph nodes 3 years after the local recurrence. We noted four histopathologic patterns in the recurrent lesions: 1) a predominantly intraepidermal pattern resembling "pseudomelanoma" as seen in recurrent "common" melanocytic nevi, 2) a compound, mostly nested pattern above or within a scar that was nearly identical to the originally biopsied Spitz nevus, 3) a nodular growth pattern that closely simulated invasive melanoma, and 4) a desmoplastic pattern resembling an intradermal desmoplastic Spitz nevus. Although the majority of recurrent lesions exhibited asymmetry and pagetoid spread, the dermal component usually had a low mitotic rate and retained architectural and cytologic maturation, which allowed distinction from invasive melanoma. Except for the metastasizing melanoma, the immunostaining pattern with S-100 and HMB-45 was identical to that previously reported for Spitz nevi. Ki67 revealed a very low proliferation rate in all cases, including the melanoma. CGH performed in 10 cases yielded results consistent with Spitz nevi in eight cases. The remaining two cases showed CGH profiles more typical of melanoma, and one of these was the above-referenced case of melanoma, proven by metastasis. Although ancillary molecular techniques such as CGH are of great help in distinguishing these from melanoma, until such techniques become widely available we advocate complete but conservative excision of any recurrent Spitz nevus.