Immunohistochemical markers in fibrohistiocytic lesions: factor XIIIa, CD34, S-100 and p75.

BACKGROUND: The distinction between dermatofibroma (DF), dermatofibrosarcoma protuberans (DFSP), and other benign and malignant cutaneous spindle cell lesions frequently requires immunohistochemical staining. CD34 and factor XIIIa are the most commonly used immunostains; however, they may exhibit aberrant expression and introduce the potential for misdiagnosis. There is some data supporting that p75 and S100A6 may be additional helpful immunohistochemical markers. METHODS: We undertook a large case series examining the use of CD34 and factor XIIIa as well as p75 and S100A6 in DF, cellular DF, DFSP, indeterminate fibrohistiocytic lesion, and scar. RESULTS: As expected, CD34 stained DFSP, although it was usually negative in DF. Factor XIIIa was generally positive in DF and negative in DFSP. There were exceptions in both cases of DF and DFSP. S100A6 was routinely negative in all entities studied. P75 was negative in all cases except DFSP, approximately half of which showed weak and/or patchy positivity. CONCLUSIONS: We conclude that to date, CD34 and factor XIIIa remain the most reliable immunohistochemical markers for DF and DFSP.

Verruciform xanthoma of the earlobe in an immunosuppressed patient.

Verruciform xanthoma (VX) is an uncommon mucocutaneous lesion of uncertain etiology. Originally thought to be limited to the oral mucosa, its occurrence in other mucosal and nonmucosal sites also has been documented. Histologically, VX is characterized by subepithelial foamy histiocytes associated with papillomatosis, parakeratosis, and dyskeratosis. Subepithelial foamy cells are lipid-containing, non-Langerhans cell histiocytes. A variety of etiologies have been proposed without much consensus, including infectious (bacterial, viral, and fungal), degenerative, reactive/ reparative, inflammatory, metabolic, reactive/ multifactorial, and immunosuppressive factors. Verruciform xanthoma of the external ear is exceedingly rare. Herein, we report a rare case of VX occurring on the earlobe at a piercing site in an immunosuppressed patient and provide a discussion of the possible pathogenetic mechanism(s).

Scleroderma and IgG4-related disease.

IgG4-related disease is a syndrome which involves lymphoplasmacytic infiltrates and soft tissue sclerosis, elevated serum IgG4 titer, and increased IgG4-positive plasma cells in a variety of tissues. Scleroderma is also characterized by fibrosis and lymphoplasmacytic infiltrates. To our knowledge, the presence of IgG4-positive cells has not been well characterized in scleroderma. A retrospective review of scleroderma and related disorders (calcinosis, raynaud's syndrome, esophageal dysmotility, sclerodactyly, telangiectasia (CREST) syndrome, progressive systemic sclerosis, morphea) was performed. Thirty-four cases of scleroderma and related disorders were identified; IgG4-positive and IgG-positive plasma cells were counted in 10 HPF and an IgG4:IgG ratio determined. A cutoff ratio of 0.3 was used to define significant elevation. Three of the scleroderma cases had IgG4:IgG greater than 0. Only 1 case had a significant elevation. Of the 3 cases with elevated ratio, IgG4-positive cells ranged from 2 to 64 (median = 14), with an IgG4:IgG ranging from 0.06 to 0.34 (median = 0.22). Similar results were produced with the other sclerosing disorders. These results suggest that scleroderma is not part of the IgG4-related disease spectrum.

Vulvar vascular tumors: a clinicopathologic study of 85 patients.

The subepidermal hormonally sensitive tissue of the vulva is anatomically unique and may give rise to a wide variety of vascular tumors. As a consequence, classifying vulvar vascular lesions has been challenging due both to the wide variety of lesions that may be encountered and the heterogeneity in reporting across several disciplines. The purpose of this study is to present an institutional experience of vulvar vascular lesions. Overall, 85 patients were identified over a 26-year period. Vascular lesions belonging to the following classes included (n, %total) benign vascular tumors (32, 38%), dilatations of preexisting vessels (31, 36%), hyperplasia/reactive (7, 8%), tumors with significant vascular component (11, 13%), malformations (3, 4%), and malignant vascular tumors (1, 1%). Two reaction patterns based on vulvar lymphatic pathology were identified: one is a stromal dominant pattern and the other is a vascular dominant pattern. Vulvar vascular malformations and true vascular malignancies, although rare, may have associated high morbidity. To accurately classify vulvar lymphatic lesions, the pathologist must carefully consider the patient's clinical history taking into account features such as preexisting lymphedema.

Multicentric reticulohistiocytosis: a unique case with pulmonary fibrosis.

BACKGROUND: Multicentric reticulohistiocytosis (MRH) is a rare disease of uncertain etiology that most commonly presents as a papulonodular cutaneous eruption accompanied by erosive polyarthritis. Although MRH is considered a systemic disorder in that it targets skin and joints, involvement of thoracic and visceral organs is uncommon. OBSERVATIONS: A woman presented with diffuse cutaneous nodules, and skin biopsy findings revealed classic features of MRH. However, she also manifested severe pulmonary symptoms. A lung biopsy specimen showed prominent histiocytic infiltrates exhibiting the same characteristic morphologic features as those seen in her skin. Furthermore, the lung biopsy findings were significant for a pattern of usual interstitial pneumonia accompanied by notable lymphoid aggregates, a pattern of interstitial lung disease typical of systemic autoimmune and inflammatory conditions. CONCLUSIONS: These findings are notable because a histiocytic pulmonary infiltrate suggestive of direct pulmonary involvement by MRH is a rare event. In addition, presentation of MRH in the setting of usual interstitial pneumonia is unique. These observations document a new clinical and histopathologic presentation of MRH that is significant for expanding the idea of MRH as a systemic disease while supporting the notion that MRH is promoted by an inflammatory milieu.

Banding pattern on polarized hair microscopic examination and unilateral polymicrogyria in a patient with steroid sulfatase deficiency.

BACKGROUND: Several forms of ichthyosis are associated with neurologic manifestations, including Sjögren-Larsson syndrome, Refsum disease, and mental retardation-enteropathy-deafness-neuropathy-ichthyosis-keratoderma (MEDNIK) syndrome. We report a case of X-linked steroid sulfatase deficiency, ichthyosis, seizures, abnormal hair banding pattern, and unilateral polymicrogyria. OBSERVATIONS: A 3-year-old Caucasian male with a history of ichthyosis since birth presented with generalized tonic seizures. Findings from a physical examination were remarkable for thin hair, retinitis pigmentosa, and poor dentition. Polarized light microscopic examination of all the hair samples demonstrated a banding pattern. Magnetic resonance imaging of the brain revealed left hemispheric polymicrogyria with decreased sulcal pattern and stable asymmetric dilation of the left lateral ventricle. Constitutional microarray revealed the typical approximately 1.5-Mb deletion of the steroid sulfatase gene. CONCLUSIONS: Steroid sulfatase deficiency is a cause of X-linked ichthyosis; however, our patient also had retinitis pigmentosa, seizures, and abnormal hair findings. The presence of abnormal hair with a banding pattern on polarized microscopy may be helpful for diagnosis; however, this pattern is not specific to this disease. In addition, to our knowledge, the presence of a malformation of cortical development has not been previously reported in patients with steroid sulfatase deficiency.

Leukocytoclastic vasculitis as the presenting feature of dermatitis herpetiformis.

BACKGROUND: Dermatitis herpetiformis is an autoimmune disease typically characterized by pruritic vesicles located on the extensor surfaces. Classic disease consists of neutrophils in the dermal papillae. Additional histopathologic findings include fibrin deposition and edema within the dermal papillae. Subepidermal vesicles also may be present. Direct immunofluorescence demonstrates granular IgA in the dermal papillae. OBSERVATIONS: A 58-year-old man with tender and pruritic erythematous macules and papules ranging from 2 to 6 mm in diameter had bilateral knee, elbow, forearm, scalp, and neck involvement. Petechiae also were present on the hands, thigh, knee, and ankle. A biopsy specimen initially demonstrated leukocytoclastic vasculitis. The results of workup for systemic vasculitis were negative. Subsequent biopsy specimens and direct immunofluorescence showed histologic evidence of dermatitis herpetiformis and leukocytoclastic vasculitis in the setting of an elevated serum IgA antitissue transglutaminase level. Marked improvement of the lesions was observed with a reduction of gluten in the patient's diet. CONCLUSIONS: Physicians should consider the possibility of dermatitis herpetiformis in patients with petechiae and leukocytoclastic vasculitis because leukocytoclastic vasculitis may be a prominent feature of dermatitis herpetiformis.

Primary cutaneous, composite, Epstein-Barr virus-associated, diffuse large B-cell lymphoma and peripheral T-cell lymphoma.

T-cell lymphomas have a broad spectrum of cutaneous involvement. Several subtypes of T-cell lymphomas are associated with Epstein-Barr virus (EBV)-driven lymphoproliferative processes. We present a case of a composite, primary, cutaneous, EBV-associated, diffuse, large B-cell lymphoma and mature T-cell lymphoma occurring in a patient with Klinefelter karyotype (47, XXY). The patient had a characteristic clinical course of a systemic mature T-cell lymphoma before the presentation of the composite, primary, EBV-associated, diffuse, large B-cell lymphoma. Although similar cases have been described in extracutaneous locations, we believe that this is the first description with a primary cutaneous presentation.

Cutaneous alternariosis microscopically mimicking blastomycosis.

A 57-year-old man status post several myocardial infarcts and heart transplantation presented with a slowly growing violaceous plaque on his lateral left knee at the site of prior minor trauma. A biopsy revealed a suppurative dermatitis with associated pseudocarcinomatous epithelial hyperplasia. There were multiple non-pigmented eosinophilic organisms with clear cytoplasmic halos within the infiltrate. A methenamine silver stain showed round to ovoid organisms of slightly variable size. Rare uni-polar budding, some of which was broad based, was apparent. A few short hyphae with indeterminate septa were also noted. Fontana-Masson, mucicarmine, Alcian blue and Fite stains were all negative. These findings suggested a diagnosis of blastomycosis. However, a fungal culture grew colonies of Alternaria species. Alternariosis has been previously shown to possess morphologic characteristics that can simulate other fungal infections. To our knowledge, a striking similarity to blastomycosis, as seen in our case, has not been previously reported. Dermatopathologists should be aware that alternariosis may mimic blastomycosis, especially when hyphal forms are rare or absent in tissue specimens. Culture is necessary for definitive classification.

Statistical analysis of the concordance of immunohistochemical stains with the final diagnosis in spitzoid neoplasms.

INTRODUCTION: The classification of spitzoid melanocytic tumors can be difficult, and pathologists rely on both histological features and clinical information to arrive at a diagnosis. We proposed that an immunohistochemical panel could be useful in classifying these neoplasms and designed a study to test the independent contribution of the panel to the final diagnosis. METHODS: We identified 121 cases previously signed out either as (1) Spitz nevus, (2) atypical spitzoid neoplasm, favor Spitz nevus, (3) atypical spitzoid neoplasm of uncertain malignant potential, (4) atypical spitzoid neoplasm, favor melanoma, and (5) spitzoid melanoma. The slides were reveiwed in random order by 4 pathologists. For the first review, the pathologists received only hematoxylin and eosin sections and patient age. Subsequently, the same pathologists interpreted the immunohistochemically stained slides (S-100A6, HMB-45, and MIB-1) on the same cases in randomized order without the benefit of either hematoxylin and eosin sections or patient age. The original diagnosis (based on a combination of clinical information, hematoxylin and eosin-stained sections and immunohistochemical stains) was the gold standard used for statistical analysis. The primary aim of the study was to determine the level of agreement between interpretions based on hematoxylin and eosin sections and age, the immunostains alone, and the gold standard, thus providing a measurement of the degree to which each of these elements contributes to the final diagnosis. The agreement between the gold standard and external review was also determined for those cases sent for external review. RESULTS: The generalized kappa statistic was 0.95 for both the hematoxylin and eosin-stained slides alone and the immunohistochemical stains alone, implying a high level of agreement among the 4 pathologists. The combined weighted kappa statistic for the comparison of hematoxylin and eosin sections and patient age to the gold standard was 0.49, and for the immunohistochemically stained slides to the gold standard 0.48, indicating that a diagnosis based on hematoxylin and eosin sections alone or immunostains alone show only a moderate and similar level of agreement with the gold standard diagnosis. Only the most controversial cases were sent for external review. The weighted kappa statistic estimate was 0.30 for the gold standard diagnosis on those cases and the external review. CONCLUSIONS: Spitzoid neoplasms remain a difficult area in dermatopathology and experts frequently disagree on the most challenging cases. An immunohistochemical panel contributes to the diagnosis of spitzoid tumors, and the contribution is statistically similar to that of hematoxylin and eosin sections and age. Interpretation remains subjective, as evidenced by the comparison of the gold standard and external review.

The staining pattern of pigmented spindle cell nevi with S100A6 protein.

BACKGROUND: Spitz nevi typically show strong diffuse staining with S100A6, whereas staining in melanomas is commonly patchy and weak. To our knowledge, S100A6 has not been studied in pigmented spindle cell nevus (PSCN), considered by many to be a variant of Spitz nevus. METHODS: Forty-six archived PSCNs were stained with S100A6 and then categorized by predominant cell size and staining pattern. RESULTS: Eighteen (55%) of the small cell predominant nevi showed patchy staining, eight showed diffuse staining and seven were negative for S100A6. Two predominantly large-celled 'PSCNs' were diffusely positive and had many histopathological attributes of classical Spitz nevi. On review, these two cases were reclassified as Spitz nevi and excluded from the remainder of this study. Of the nevi with mixed cell size, one had no expression of S100A6. In the remaining tumors, the small cells showed patchy staining in eight (80%) and diffuse staining in two (20%). The large cells showed patchy staining in four (40%) and diffuse staining in six (60%). CONCLUSION: In contrast to the strong diffuse S100A6 staining typical of Spitz nevi, the small spindle cells of PSCN commonly show patchy staining or fail to stain completely. In melanocytic neoplasms composed of small spindle cells, patchy S100A6 staining should not be interpreted as evidence of supporting a diagnosis of melanoma.

Evaluation of 39 cases of pediatric cutaneous head and neck melanoma.

BACKGROUND: Studies examining head and neck (H&N) melanoma in the pediatric population are scarce. OBJECTIVE: The goal of this study is to describe pediatric H&N melanoma with the intent of increasing understanding of the course of disease. METHODS: The Duke Melanoma Database and Duke Tumor Registry Database were searched for patients with a diagnosis of melanoma occurring on the H&N before age 18 years, with exclusion of ocular/mucosal/aerodigestive melanomas. RESULTS: Queries yielded 39 Caucasian pediatric patients, 24 (61.5%) of them male. The mean age at diagnosis was 14.2 years (15 years, median). The primary sites were represented as follows: cutaneous auricular (1/39, 2.6%), facial (15/39, 38.5%), and scalp/neck (23/39, 59%). The follow-up time ranged from 2 months to 23 years with a median of 9.9 years (95% confidence interval: 6.2-13 years). At the time of follow-up, there were 12 (12/39, 30.8%) melanoma-associated deaths. The anatomic distribution of primary melanoma for these 12 patients follows: 4 (33.3%) facial and 8 (66.7%) scalp/neck. Histologic data revealed 24 (61.5%) tumors classified as superficial spreading melanoma with nodular melanoma (12.8%) a distant second. The mean Breslow depth for patients with melanoma-related mortality was 2.4 mm, compared with 1.8 mm for those who were alive at last follow-up. LIMITATIONS: Small sample size limited this study. CONCLUSION: This study found that the majority (59%) of H&N melanomas presented as scalp or neck lesions with a predilection for adolescents and boys. Those who experienced melanoma-related mortality had thicker lesions. Superficial spreading melanoma was the most common subtype.

Cutaneous metastatic cholangiocarcinoma: a report of three cases and review of the literature.

Cutaneous metastasis from cholangiocarcinoma is an extremely rare event. Herein, we present three cases with review of the literature. Case 1 is that of a young female with scalp metastasis. Cases 2 and 3 involve cutaneous metastasis to the sites of prior biliary drains, one occurring in a young female with a history of multiple biliary surgeries and one in a male with a history of sclerosing cholangitis. Review of the literature shows that the presentation of cutaneous metastases from cholangiocarcinoma can vary in terms of anatomic location and clinical features. The pathological and immunohistochemical profile of metastatic cholangiocarcinoma can be non-specific, and accurate diagnosis relies in part on clinical correlation. In summary, metastatic disease should always be included in the differential diagnosis of cutaneous lesions in patients with known malignancy.

Neuronal ceroid lipofuscinosis diagnosed via skin biopsy.

We aim to report that skin biopsy, a non-invasive test by neurological standards, may lead to a diagnosis. A 4-year-old male presented with a 2-year history of epilepsy and progressive developmental regression. The patient had a mildly elevated ammonia level; however, evaluation for the accumulation of excess serum amino acids and evaluation of urine for organic acids was negative. MRI revealed cerebral atrophy, and an electroencephalogram demonstrated multifocal sharp and slow waves. Due to the progressive degenerative neurologic presentation, a neurologic storage disease was favored. An axillary skin biopsy was performed, revealing eosinophilic intra-cytoplasmic inclusions within the eccrine glands. A periodic acid-Schiff stain also highlighted these inclusions. Electron microscopic studies demonstrated characteristic multiple membrane-bound inclusions within the eccrine epithelial cells, containing curvilinear inclusion material characteristic of neuronal ceroid lipofuscinosis. The clinical, histological, electron microscopic and enzymatic studies were diagnostic of late-infantile onset neuronal ceroid lipofuscinosis.

CD4/CD8 double negative pagetoid reticulosis: a case report and literature review.

Pagetoid reticulosis is an indolent primary cutaneous T-cell lymphoma. It typically presents as a solitary and slowly growing patch or plaque on the extremity, histologically characterized by an acanthotic epidermis infiltrated with atypical lymphocytes. Here, we present histological, immunophenotypical and molecular findings of a 29-year-old Jamaican man with bilateral wrist plaques. Histology showed marked acanthosis, hyperkeratosis and an intraepidermal infiltration consisting of large atypical lymphocytes. Immunohistochemical stains showed CD3 and CD5 positive T cells with significant loss of CD7, double negative CD4 and CD8 and strong positive CD30. Molecular analysis showed a monoclonal T-cell receptor (TCR) gamma gene rearrangement. Review of the literature confirms that the immunophenotype of pagetoid reticulosis is variable with decreasing frequency of CD8+ cytotoxic/suppressor T cell, CD4+ helper T cell and least commonly CD4/CD8 double negative phenotypes. Although CD4/CD8 double negative phenotype appears to be associated with higher proliferation index, it does not appear to confer prognostic significance.