Centrofacial Balamuthiasis: case report of a rare cutaneous amebic infection.

Free-living amebae are ubiquitous in our environment, but rarely cause cutaneous infection. Balamuthia mandrillaris has a predilection for infecting skin of the central face. Infection may be restricted to the skin or associated with life-threatening central nervous system (CNS) involvement. We report a case of a 91-year-old woman, who presented with a non-healing red plaque over her right cheek. Several punch biopsies exhibited non-specific granulomatous inflammation without demonstrable fungi or mycobacteria in histochemical stains. She was treated empirically for granulomatous rosacea, but the lesion continued to progress. A larger incisional biopsy was performed in which amebae were observed in hematoxylin-eosin stained sections. These were retrospectively apparent in the prior punch biopsy specimens. Immunohistochemistry and polymerase chain reaction studies identified the organisms as Balamuthia mandrillaris. Cutaneous infection by B. mandrillaris is a rare condition that is sometimes complicated by life-threatening CNS involvement and which often evades timely diagnosis due to its rarity and nonspecific clinical manifestations. Moreover, these amebae are easily overlooked in histopathologic sections because of their small number and their resemblance to histiocytes. Dermatopathologists should be familiar with the histopathologic appearance of these organisms and include balamuthiasis and other amebic infections in the differential diagnosis of granulomatous dermatitis.

Cutaneous presentation of disseminated histoplasmosis as a solitary peri-anal ulcer. Case report and discussion.

Disseminated histoplasmosis has a diverse and non-specific range of clinical signs and symptoms. In a significant minority of patients, cutaneous lesions are apparent at the time of initial presentation, affording an opportunity to establish the diagnosis from a skin biopsy. The most frequently reported clinical scenario in immunocompromised patients with cutaneous involvement is that of multiple papulo-nodular lesions on the face, trunk or extremities. The following report features an immunocompetent patient who presented with a solitary ulcerated plaque on the buttocks close to the anal verge. This case presentation underscores the broad spectrum of clinical presentations as well as the potential for diagnostic confusion with protozoa such as Leishmania or Trypanosoma species during histopathologic examination if special stains for fungal organisms are not performed.

Granulomatous scleromyxedema: case report and literature review.

Scleromyxedema is a rare and frequently disabling disease characterized by generalized waxy papules, skin induration, and cardinal histological features of dermal fibroblastic proliferation, thickened collagen, and mucin deposition. A monoclonal gammopathy is almost always present with rare progression to multiple myeloma. We describe the case of a 54-year-old man who presented with a rash in the setting of a new medication and histological features suggesting a granulomatous drug reaction. Despite discontinuation of the medication, the rash persisted and a second biopsy confirmed an interstitial granulomatous pattern. Serum protein electrophoresis identified the presence of a biclonal gammopathy leading to a diagnosis of granulomatous scleromyxedema. Review of the medical literature reveals only a handful of well-documented similar cases of this rare variant. It is important for pathologists and clinicians to be familiar with this condition to facilitate timely diagnosis and optimal clinical management of these patients.

Cutaneous angiosarcoma clinically presenting as progressive solid facial edema in a 43-year-old male.

Cutaneous angiosarcoma of the head and neck is a rare, highly malignant neoplasm; prognosis is heavily influenced by tumor size, resectability, and stage at initial diagnosis. Most patients present with one to several erythematous to violaceous patches, plaques, or nodules. However, the clinical presentation is highly variable and leads to delayed diagnosis. We report cutaneous angiosarcoma in a 43-year-old man who presented with an 11-month history of progressive solid (non-pitting) edema involving his entire face, scalp, eyelids, and neck without characteristic clinical features of cutaneous angiosarcoma. A skin biopsy had shown non-specific findings consistent with solid facial edema or rosacea. Various etiologies were considered but there was no significant improvement after directed medical therapy. Repeat skin biopsies revealed angiosarcoma involving the dermis and sub-cutis. Computed tomography (CT) of the chest showed multiple lung nodules bilaterally and a lytic lesion in the T6 vertebra consistent with metastases. He was treated with single agent chemotherapy (paclitaxel), and had a partial response that restored his ability to open both eyes spontaneously; However, his edema has recently progressed 7 months after diagnosis. This is a rare example of cutaneous angiosarcoma presenting as progressive solid facial edema, which underscores the diverse range of clinical manifestations associated with this neoplasm.

Langerhans cell sarcoma in a patient with hairy cell leukemia: common clonal origin indicated by identical immunoglobulin gene rearrangements.

Histiocytic/dendritic cell sarcomas are rare tumors, a few of which have been reported in association with B-cell lymphoma/leukemia. Isolated reports have documented identical immunoglobulin gene rearrangements suggesting a common clonal origin for both the sarcoma and the B-cell neoplasm from individual patients. We report a case of a 75-year-old male with hairy cell leukemia who subsequently developed Langerhans cell sarcoma 1 year after his primary diagnosis of leukemia. The bone marrow biopsy containing hairy cell leukemia and skin biopsies of Langerhans cell sarcoma were evaluated by routine histology, immunohistochemistry, flow cytometric immunophenotyping and PCR-based gene rearrangement studies of the immunoglobulin heavy chain and kappa genes. The hairy cell leukemia showed characteristic morphologic, immunohistochemical and flow cytometric features. The Langerhans cell sarcoma showed pleomorphic cytology, a high mitotic rate and characteristic immunohistochemical staining for Langerin, S100 and CD1a. There was no evidence of B-cell differentiation or a background B-cell infiltrate based on the absence of immunoreactivity with antibodies to multiple B-cell markers. Identical immunoglobulin gene rearrangements were identified in both the hairy cell leukemia and Langerhans cell sarcoma specimens. Despite the phenotypic dissimilarity of the two neoplasms, identical immunoglobulin gene rearrangements indicate a common origin.

Eccrine hidradenitis sine neutrophils: a toxic response to chemotherapy.

We present a case of hidradenitis occurring in a patient after chemotherapy for acute myeloid leukemia (AML) in the setting of profound neutropenia. Neutrophilic eccrine hidradenitis (NEH) presents as tender erythematous papules and plaques and is often associated with chemotherapy for AML. NEH is postulated to be due to toxic injury to the sweat glands followed by neutrophilic inflammation. Alternatively, some hypothesize that NEH represents a primary neutrophilic process. Our patient's clinical presentation was similar to previously reported cases of NEH; however, degenerative changes of the sweat ducts were noted on microscopy without neutrophilic inflammation. She had fewer than 0.01 thousand neutrophils per microliter for 4 days preceding the biopsy. At the same time, a separate area of superficial skin infection developed because of Staphylococcus epidermidis and also lacked neutrophilic inflammation. The similar clinical course and shared histopathologic features between our case and NEH argue that neutrophils are a secondary response to a toxic effect rather than the primary effector in NEH. Neutrophil-poor variants of hidradenitis, both infectious and due to drug toxicity, should be considered diagnostically in neutropenic patients.

Lymphomatoid hypersensitivity reaction to levofloxacin during autologous stem cell transplantation: a potential diagnostic pitfall in patients treated for lymphoma or leukemia.

Drug-associated cutaneous lymphomatoid hypersensitivity reactions are rare eruptions that can clinically and microscopically mimic a bona fide lymphomatous process. Clinically, the appearance ranges from papulosquamous to purpuric. Histopathologically, these reactions simulate a wide variety of lymphoma subtypes; the most frequently reported examples resemble mycosis fungoides. We report a 61-year-old female who developed a purpuric eruption prior to engraftment of an autologous hematopoietic stem cell transplant for stage IV mantle cell lymphoma. Skin biopsies showed a superficial perivascular and interstitial infiltrate of large, immature-appearing mononuclear cells associated with spongiosis, papillary dermal edema and erythrocyte extravasation. The cells were immunoreactive for T-cell markers and lacked B-cell marker expression, excluding recurrence of the underlying mantle cell lymphoma as a diagnostic possibility. The cutaneous eruption was temporally linked to levofloxacin administration and resolved after discontinuation of this medication. This is the first report of a lymphomatoid hypersensitivity reaction associated with fluoroquinolone use. The histopathologic features presented in this paper underscore the potential for misdiagnosis of such lesions as lymphoma or acute myeloid leukemia, particularly in the setting of hematopoietic stem cell transplantation for underlying lymphoma or leukemia. Clinical correlation, morphologic comparison to the original malignancy and immunohistochemical studies aid the dermatopathologist in rendering the correct diagnosis.

Occupational hazard for pathologists: microscope use and musculoskeletal disorders.

The association of prolonged microscope use with the development of chronic pain syndromes has been recognized for nearly 3 decades; yet most pathologists are not well-informed about this hazard until after they develop a problem. The purpose of this article is to make pathologists aware of this risk, discuss current pathogenetic models, and encourage them to proactively integrate prevention strategies into their daily lives.

Immunohistochemical evaluation of p16INK4A, E-cadherin, and cyclin D1 expression in melanoma and Spitz tumors.

We evaluated the usefulness of immunohistochemical examination for E-cadherin, p16, and cyclin D1 in discriminating melanoma from Spitz tumors. Immunoperoxidase staining was performed on formalin-fixed tissue specimens from 46 Spitz tumors and 42 concurrent melanoma specimens. The percentages of immunoreactive melanocytes in the epidermis and dermis were estimated semiquantitatively. Qualitatively abnormal immunoreactivity patterns were also tabulated. Dermal p16 immunoreactivity was the best quantitative discriminator: decreased nuclear immunoreactivity (<25% of dermal melanocytes) was 3-fold more likely in melanoma than in Spitz tumors (P = .004). Loss of both nuclear and cytoplasmic dermal p16 immunoreactivity was 8-fold more likely in melanoma (P = .01). Qualitative irregularities in the zonal distribution of E-cadherin immunoreactivity were 2-fold higher in melanoma (P = .01), but these were often focal or subtle. There was no statistically significant difference in cyclin D1 immunoreactivity. In atypical Spitz tumors, the dermal p16 immunoreactivity and frequency of qualitative E-cadherin abnormalities were intermediate between those of ordinary Spitz nevi and melanoma. Also, contrasting immunoreactivity patterns were helpful in determining Breslow thickness in specimens containing melanoma and contiguous dermal nevi.

Granulomatous dermatitis with pseudoxanthoma elasticum-like changes: report of a case in a patient with cystic fibrosis.

BACKGROUND: There is scant literature that documents pseudoxanthoma elasticum (PXE)-like histologic changes in the setting of inflammatory skin diseases. This article documents granulomatous dermatitis with PXE-like changes in a patient with cystic fibrosis. This is the first report of its kind, to our knowledge. OBSERVATIONS: A 33-year-old woman with cystic fibrosis developed a papular eruption on the flexural surfaces of the upper and lower extremities, which was initially treated with prednisone. A punch biopsy showed granulomatous inflammation and associated PXE-like changes. The combined histologic and clinical findings were most consistent with granuloma annulare. There was no family history of PXE or clinical manifestations of PXE. The rash gradually resolved itself over the next several months. CONCLUSIONS: There are few publications that document PXE-like changes in association with various inflammatory skin conditions. Thus, the clinical significance of this finding remains uncertain. This case and previous reports are discussed in the context of current molecular and genetic knowledge. It is hoped that greater awareness of this phenomenon will promote further investigation and elucidation of the clinical and biologic significance of PXE-like changes observed in biopsies of inflammatory skin disorders.

Subclassification of desmoplastic melanoma: pure and mixed variants have significantly different capacities for lymph node metastasis.

BACKGROUND: There is disagreement about the behavior and optimal management of desmoplastic melanoma (DM), particularly regarding the incidence of lymph node (LN) involvement. Recently, investigators have noted the frequently heterogeneous histologic composition of DM and have found significant differences between pure desmoplastic melanoma (PDM) (>or=90% comprised of histologically typical DM) and mixed desmoplastic melanoma (MDM) [>or=10% DM and >10% conventional melanoma (CM)]. METHOD: We reviewed 87 cases of DM comparing the histologic and clinical features of PDM (n = 44) to MDM (n = 43). RESULTS: At surgical staging, there were LN metastases in 5 of 23 (22%) MDM patients, whereas all 17 PDM patients had negative LN biopsies (0%) (p = 0.04). PDM was less often clinically pigmented (36% vs. 67%) and had a lower mean mitotic index (1.3 vs. 3.0). CONCLUSIONS: There are differences between PDM and MDM, the most important of which is the incidence of LN involvement. Our findings support the clinical utility of classifying DM into pure and mixed subtypes because the negligible rate of nodal involvement in PDM does not support the routine performance of sentinel LN biopsy in this subgroup of melanoma patients. In contrast, the incidence of LN involvement in MDM is comparable to that of CM.

Subungual Bowen disease in a patient with epidermodysplasia verruciformis presenting clinically as longitudinal melanonychia.

Epidermodysplasia verruciformis (EV) is a rare autosomal-recessive condition associated with a predisposition to infection with specific types of human papillomaviruses. A spectrum of wart-like lesions on the face, dorsa of the hands, and legs are characteristic clinical findings. Lesions usually develop in early childhood, persist, and may eventuate in cutaneous squamous cell carcinoma, usually in sun-exposed areas. These lesions are locally destructive and sometimes metastasize. We present a case of a 34-year-old African American woman with EV with a 9-month history of a right index finger ungual longitudinal pigmented band and nail splitting. Biopsy showed hyperkeratotic and parakeratotic subungual epithelium with verrucous hyperplasia. The superficial keratinocytes showed koilocytic changes. In addition, there was extensive, focally full-thickness keratinocyte dysmaturation with variable nuclear atypia and numerous mitotic figures, without apparent invasion. An associated melanocytic hyperplasia (confirmed by Melan-A stain), composed of large, pigment-laden dendritic melanocytes, was present without appreciable atypia or pagetoid spread. The findings are of a squamous cell carcinoma in situ arising in association with EV with incidental melanocytic hyperplasia. To the best of our knowledge, this is first report of a subungual presentation of this condition with associated melanonychia.

CD4+/CD56+ hematodermic neoplasm: report of a rare variant with a T-cell receptor gene rearrangement.

CD4+/CD56+ hematodermic neoplasm (HN), formerly known as a blastic natural killer (NK) cell lymphoma, is a rare subtype of a cutaneous dendritic cell neoplasm notable for highly aggressive behavior. The characteristic features are: expression of the T-helper/inducer cell marker CD4 and the NK-cell marker CD56 in the absence of other T cell or NK-cell specific markers. In particular, CD3 (surface or cytoplasmic) and CD2 are not expressed. Although T-cell receptor (TCR) genes are generally reported to be in a germline configuration, we present an unusual variant of a CD4+/CD56+ HN with a clonal rearrangement of TCR genes. This feature of a CD4+/CD56+ HN has been only rarely reported. Recognition of the presence of clonal TCR gene rearrangements in a small subset of CD4+/CD56+ HN is important to avoid misdiagnosis of this entity as an unusual variant of a cutaneous T-cell lymphoma.

Oculocutaneous oncocytic tumors: clinicopathologic and immunohistochemical study of 2 cases with literature review.

Oculocutaneous oncocytic tumors (OCOTs) are uncommon neoplasms that have been reported only rarely in the dermatopathology literature and whose immunophenotypic profile has not been well characterized. The clinical, histologic, and immunophenotypic features of 2 cases seen by the authors were assessed, and relevant publications in the literature were reviewed. Both patients with OCOTs were adult women with gradually enlarging, asymptomatic lesions involving the caruncle; they were locally excised. Histologically, the tumors were well-circumscribed nodules comprised of large oxyphilic cells arranged in confluent sheets and forming glandular spaces with secretory material. Microcystic areas and sparse intermingled goblet-cells were also apparent. Nuclear atypia and infiltrative growth were absent. Mitotic activity was absent in one case; a single mitotic figure was identified in the other. Immunostains demonstrated uniform expression of pankeratin and mitochondrial antigens. Both neoplasms were also labeled for markers associated with cutaneous adnexal, lacrimal, and minor salivary glandular tissue, including alpha-1-antitrypsin, gross cystic disease fluid protein-15, carcinoembryonic antigen, lysozyme and MUC1; each case expressed 4 of the 5 substances. Some cells expressed cytokeratins 5/6 and p63 consistent with the presence of basal-type differentiation in a subset of cells. No definite evidence of myoepithelial differentiation was demonstrated, as stains for smooth muscle actin, muscle-specific actin, and S100 protein were negative. Estrogen and progesterone receptor proteins were absent; strong cytoplasmic immunoreactivity for androgen receptor protein was evident, but nuclear staining was absent. The authors conclude that OCOTs show glandular differentiation. A review of the literature disclosed that none of these lesions arising in the caruncle behaved aggressively, in contrast to occasional tumors in other oculocutaneous sites.