A series of melanomas smaller than 4 mm and implications for the ABCDE rule.

BACKGROUND: Although multiple studies have reported that a significant number of melanomas have diameters of less than or equal to 6 mm at the time of diagnosis, there has been only one series evaluating the proportion of melanomas less than 4 mm in diameter. OBJECTIVE: The objective of this study was to determine the proportion of melanomas, in a single-practitioner, general dermatology practice, with clinical diameters less than 4 mm. METHODS: Information regarding each new diagnosis of melanoma had been recorded during the study period of 2000-2004. Patient records and pathology reports were examined from these patients. RESULTS: Thirteen (13.7%) of the 95 melanomas had diameters less than 4 mm at the time of presentation, including five invasive and eight in situ melanomas. The defining clinical characteristic of these lesions was intensity of pigment. Three of these 13 melanomas, including one invasive and two in situ lesions, showed features of regression. CONCLUSIONS: The findings of this study support those authors who have suggested elimination of the 6-mm diameter criterion in the ABCDE rule. In addition, this study provides further evidence that dark colour as a diagnostic criterion for melanoma should be given more emphasis. The substitution of 'D' to represent dark instead of diameter is worthy of consideration to enhance the value of the ABCDE mnemonic.

Angiotropic malignant melanoma: a rare pattern of local metastases.

We report a case of angiotropic malignant melanoma and review previously reported cases. Vessel walls should be scanned for tumor cells in biopsy and re-excision specimens of melanoma.

Clinicopathologic variants of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinomas (SCC) are one of the most common malignancies, which, with early recognition, may be curable. These tumors represent a broad spectrum of disorders with many significant clinical, morphologic, and etiologic distinctions. The objective of this article is to review the important clinicopathologic features of SCC with particular emphasis on important recent developments, practical application, and their relevance to the practice of pathology. The most pertinent literature of the last 5 years was reviewed and capsulized. Appropriate histologic interpretation and clinical management of patients with cutaneous SCC requires a comprehensive understanding of the latest advances in the broad field of dermatopathology. Squamous cell carcinoma of the skin represents a complex group of disease subtypes, each with its own characteristics, which may influence morphologic diagnosis as well as treatment and clinical management.

Mucoepidermoid/adenosquamous carcinoma of the skin: presentation of two cases.

BACKGROUND: Mucoepidermoid carcinoma is a relatively common neoplasm of the major and minor salivary glands comprising 10-30% of primary carcinomas. They may involve the skin through direct extension, metastases, and rarely, as a primary focus (adenosquamous carcinoma). OBJECTIVE: To discuss through case reports, the nomenclature, histology, clinical course, and treatment of mucoepidermoid/adenosquamous carcinoma. METHODS: We present a case of mucoepidermoid carcinoma primary to an upper eyelid accessory lacrimal gland with direct cutaneous extension and a case of primary cutaneous adenosquamous carcinoma of the scalp. RESULTS: An eyelid neoplasm of lacrimal origin was initially treated with Mohs micrographic surgery (MMS), requiring an orbital exenteration to achieve a tumor-free plane. In the second case, a primary scalp lesion was cleared with MMS. Neither patient has had local recurrence or metastases. CONCLUSION: Correct diagnosis is crucial to pursuing adequate treatment for this aggressive neoplasm. We support the use of MMS to achieve local control.

Eccrine porocarcinoma treated with Mohs micrographic surgery: A report of five cases.

BACKGROUND: Eccrine porocarcinoma is a rare, locally aggressive, potentially fatal neoplasm. While wide local excision has traditionally been the treatment of choice, recurrences following excision are common. OBJECTIVE: The purpose of this study was to review the traditional treatments of eccrine porocarcinoma as well as to introduce Mohs micrographic surgery as an alternative to wide local excision. METHODS: We reviewed all cases of eccrine porocarcinoma seen at Emory University between 1985 and 1999. All cases were treated definitively with Mohs micrographic surgery. The clinical characteristics and outcome of each case are summarized. RESULTS: Five patients with eccrine porocarcinoma were treated with Mohs micrographic surgery. There have been no recurrences to date, with an average follow-up of 2.1 years (ranging from 5 months to 4 years). CONCLUSION: Follow-up of five patients supports the view that Mohs micrographic surgery may be an effective treatment for eccrine porocarcinoma.

Indeterminate melanocytic proliferations of the conjunctiva.

OBJECTIVE: To test the hypothesis that a subset of conjunctival melanocytic proliferations exists that cannot be reproducibly classified as benign, malignant, or indeterminate. METHODS: Three groups of excisional biopsy specimens of conjunctival melanocytic proliferations were evaluated by a panel of 5 ophthalmic pathologists. These groups included lesions that we considered to represent benign (group 1 [n = 5]), malignant (group 2 [n = 5]), and indeterminate melanocytic proliferations (group 3 [n = 5]). The panel classified the same sections in all 3 groups in a randomized, masked fashion, first without and then with a clinical history of patient age, sex, and race. The kappa statistic was used to quantify the degree of agreement among observers. RESULTS: There was strong concordance among the panel members for both group 1 (benign [kappa = 0.76]) and group 2 (malignant [kappa = 0.70]) melanocytic proliferations. There was no concordance of the panel for group 3 (indeterminate) lesions (kappa = -0.045). The concordance for groups 1 and 2 and lack of concordance for group 3 lesions were independent of knowledge of clinical history of age, sex, and race. CONCLUSION: A subset of melanocytic proliferations of the conjunctiva exists that cannot be reproducibly classified by pathologists as benign, malignant, or indeterminate.

Indeterminate melanocytic proliferations of the conjunctiva.

PURPOSE: The purpose of this study is to test the hypothesis that a subset of conjunctival melanocytic proliferations exists that cannot be reproducibly classified as benign, malignant, or indeterminate. METHODS: Three groups of excisional biopsy specimens of conjunctival melanocytic proliferations were evaluated by 5 ophthalmic pathologists. These groups included lesions that were considered by the authors to represent benign (Group 1, n = 5), malignant (Group 2, n = 5) and indeterminate melanocytic proliferations (Group 3, n = 5). The panel classified the same sections in all 3 groups in a randomized, masked fashion, first without and then with a clinical history of patient age, sex and race. The kappa statistic (k) was used to quantify the degree of agreement among observers. RESULTS: There was strong concordance among the panel for both Group 1 (benign, k = 0.76) and Group 2 (malignant, k = 0.70) melanocytic proliferations. There was no concordance of the panel for Group 3 (indeterminate) lesions (k = -0.045). The concordance for Groups 1 and 2 and lack of concordance for Group 3 lesions were independent of knowledge of clinical history of age, sex, and race. CONCLUSIONS: A subset of melanocytic proliferations of the conjunctiva exists that cannot be reproducibly classified by pathologists as benign, malignant, or indeterminate.

In vivo human melanoma cytokine production: inverse correlation of GM-CSF production with tumor depth.

Melanomas produce multiple cytokines which may influence their growth in vivo. Experimental evidence suggests that granulocyte macrophage-colony stimulating factor (GM-CSF) can induce a potent anti-melanoma response. whereas interleukin-8 (IL-8) may act as a growth factor in human melanoma. Little is currently known regarding the production of these cytokines by human melanoma in vivo. In this study we tested the hypothesis that endogenous production of GM-CSF and IL-8 can be correlated with the depth of human malignant melanoma surgical specimens. We examined 45 melanocytic human tissue samples consisting of 27 primary cutaneous melanomas, 9 metastatic melanomas, and 9 dysplastic nevi for in vivo GM-CSF and IL-8 production using immunohistochemistry. The majority of thin melanomas (< or = 0.76 mm) stained highly positive for GM-CSF with little or no staining for IL-8 whereas the medium (>0.76- < or = 4.0 mm) and thick (>4.0 mm) melanoma specimens showed little or no staining for GM-CSF and significant amounts of IL-8 staining. Metastatic melanoma as well as dysplastic nevi specimens had little or no GM-CSF and IL-8 staining. These results support the hypothesis that endogenous melanoma cytokines such as GM-CSF and IL-8 with opposing effects on tumor progression play an important role in melanoma growth and regulation.

Lichen planus-like histopathologic characteristics in the cutaneous graft-vs-host reaction. Prognostic significance independent of time course after allogeneic bone marrow transplantation.

BACKGROUND: The discrimination between acute and chronic graft-vs-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) is important because the treatment regimens and prognosis differ. OBJECTIVES: To identify whether accepted histopathologic criteria of a graft-vs-host reaction (GVHR) alone or in combination accurately reflect clinical phase of disease, to correlate patterns with clinical outcome, and to identify any concordance between inflammation and epidermal changes of a GVHR. DESIGN: Skin biopsy specimens were analyzed according to histologically defined standards. SETTING: This study was performed in a tertiary care hospital. PATIENTS: One hundred seventy-three skin biopsy specimens (10 days before to 1326 days after BMT) from 83 patients undergoing allogeneic BMT for various malignant neoplasms were selected for study. A consecutive 12-month sample was used. MAIN OUTCOME MEASURES: The main measures in this study were statistical correlations between histopathologic findings and time after BMT, the outcome of BMT, and the correlations between selected histopathologic criteria. RESULTS: Fully evolved histologic features of chronic lichenoid GVHR in the specimens occurred across a wide time range (33-832 days after BMT) and were associated with a 5.6-fold increased risk for death (P = .02) from GVHD. Histologic features of acute GVHR in the specimens also occurred across a wide time range (14-481 days after BMT) and were associated with a 2.2-fold increased risk for death; this finding was not statistically significant (P = .11). Inflammation of the upper dermis was significantly associated with acanthosis and epidermal cell necrosis (P < .001 and P < .001, respectively, for bandlike pattern), confirming the importance of this finding as a criterion for the diagnosis of a GVHR. Blinded evaluation of a subset of specimens for the diagnosis of acute vs chronic GVHR resulted in wide interobserver variation. CONCLUSIONS: This study demonstrates the following: specific histologic parameters in skin biopsy specimens do not consistently separate acute from chronic GVHD as defined by days after BMT; independent of time course, fully evolved histopathologic characteristics of a lichen planus-like GVHR is associated with a greater likelihood of death from GVHD; and identification of upper dermal inflammation correlates with the epidermal features of GVHR and should be included in the diagnostic scheme.

Spindle cell lipoma is strongly CD34 positive. An immunohistochemical study.

Spindle cell lipoma (SCL) is an uncommon soft tissue neoplasm that may provide diagnostic difficulty to the histopathologist. Four retrospectively identified SCLs were evaluated immunohistochemically with a broad panel of antibodies (CD34, factor XIIIa, S-100, actin and factor VIII). All four SCLs were strongly CD34 positive (95 to 100% of cells) and focally factor XIIIa positive (average 16% of cells). Tumor cells were S-100, actin and factor VIII negative. Dermatofibrosarcoma protuberans, neurofibroma, schwannoma and angiolipoma are CD34 positive tumors that have some similar histologic features to SCL and may be considered in the differential diagnosis. Differentiation is possible using a broad panel of immunostains and routine diagnostic criteria.

Alopecia: histologic diagnosis by transverse sections.

Histologic evaluation for alopecia can be difficult and in part can be attributed to confusing categorization and limited information derived from examination of traditionally prepared biopsy specimens. The transverse section technique has many advantages, and with experience is the preferable method for evaluating specimens for alopecia. Using this technique, numerous follicles can easily be seen in one tissue profile allowing evaluation of follicular density, follicular unit morphology, and follicular growth dynamics, ie, anagen-telogen ratio. Specimens are categorized as scarring or nonscarring alopecia, and further diagnostic criteria discussed herein assist the pathologist in making specific diagnoses of nonscarring and scarring alopecias. Scarring alopecia may be primary or secondary, and primary scarring alopecias are further classified as lymphocyte-associated and neutrophil-associated. Although the clinical impression is very important in diagnosing alopecia, transversely sectioned biopsy specimens can greatly aid the diagnosis and management of patients with alopecia.

Nodular scleroderma.

We describe a 40-year-old woman with systemic scleroderma who had hundreds of firm nodules that developed on the trunk and upper extremities during several months. We briefly review previously reported cases of this rare variant of scleroderma.

Congenital melanocytic nevi and DNA content. An analysis by flow and image cytometry.

BACKGROUND: Potential risk factors for the development of melanoma in congenital melanocytic nevi (CMN) are not well established. DNA aneuploidy may constitute such a risk factor but has not been sufficiently studied in CMN. METHODS: In the present study, DNA analysis of eight giant CMN, nine medium CMN (1.5-20 cm), and eight small CMN (< 1.5 cm) was assessed by flow cytometry and selected lesions (six nevi) by DNA image cytometry. DNA content was correlated with patient age, nevus size, and degree of cytologic atypia. RESULTS: DNA aneuploidy was detected by flow cytometry in two giant CMN from adult patients and in a small CMN from a child. DNA aneuploidy was not observed in any of the six CMN studied by image cytometry, although an increased S-phase was noted in a markedly atypical giant CMN. No DNA aneuploidy was detected in medium-sized CMN or in the CMN of nine patients 1 year of age or younger. CONCLUSION: In contrast to previous studies, it was observed that abnormal DNA content does tend to correlate with cytologic atypia, particularly in giant CMN with atypia or melanoma, in adults. Conversely, frank DNA aneuploidy in any CMN in children younger than 1 year of age, irrespective of histologic findings, was not detected. Finally, based on these limited studies, greater sensitivity of image over flow cytometry for detection of DNA aneuploidy cannot be verified.

Disseminated strongyloidiasis with cutaneous manifestations in an immunocompromised host.

Recognition of the characteristic cutaneous eruption of disseminated strongyloidiasis can be crucial for early diagnosis and treatment of this potentially fatal infestation. We describe a corticosteroid-dependent elderly man who had a purpuric eruption. Filariform larvae of Strongyloides stercoralis were found in dermal granulomas and also in the sputum.

Diffuse dermal angiomatosis: a variant of reactive cutaneous angioendotheliomatosis.

Reactive angioendotheliomatosis (RA) is a rare, benign disease. Affected patients present with self-limited, erythematous to violaceous plaques. The clinical lesions are due to intravascular hyperplasia of cytologically banal endothelial cells in the dermis. We report 2 patients who presented with ulcerated, violaceous plaques on the lower extremities. Both had severe peripheral vascular atherosclerotic disease requiring bypass grafts. Unlike previously described cases of RA, our patient's lesions were due to a diffuse proliferation of endothelial cells in the reticular dermis with only minimal, focal intravascular proliferation of these cells. Positive immunostaining with antibodies to Factor VIII-related and CD34 antigens adds evidence that the proliferated cells in the dermis were endothelial cells.

Intradermal bleomycin injections into normal human skin. A histopathologic and immunopathologic study.

BACKGROUND: Intralesionally injected bleomycin is a useful agent for the treatment of recalcitrant warts. The mechanism of action in wart therapy has been thought to be due to DNA and antiviral effects. To further characterize the inflammatory response to intralesional bleomycin injections, we examined the clinical, histologic, and immunopathologic response to intradermal bleomycin injections in normal human skin. RESULTS: Four volunteers were each given four intradermal bleomycin injections (0.01 to 0.5 U/mL) into normal human skin to establish a dose response. These injections induced a localized time and dose-dependent inflammatory reaction and persistent postinflammatory hyperpigmentation. Nine biopsy specimens from two volunteers were taken at different time points after intradermal bleomycin injections (0.1 to 1.0 U/mL) into normal human skin. Routine histologic study demonstrated dyskeratosis and necrosis of epidermal keratinocytes and eccrine epithelium associated with a prominent neutrophilic infiltrate, closely resembling histopathologic findings seen in neutrophilic eccrine hidradenitis. Expression of HLA-DR and intercellular adhesion molecule 1 was induced on keratinocytes; intercellular adhesion molecule 1 was upregulated, and endothelial leukocyte adhesion molecule 1 was induced on superficial dermal blood vessels. CONCLUSIONS: These findings suggest that intradermal bleomycin injection is either directly or indirectly cytotoxic to keratinocytes and eccrine epithelium. Expression and upregulation of activation antigens and cell adhesion molecules suggest that a cellular immune system response and proinflammatory cytokine secretion occur after intralesional bleomycin injection into normal human skin. Histopathologic findings at some injection sites resemble neutrophilic eccrine hidradenitis.