David J. DiCaudo

The clinical behavior of desmoplastic melanoma

BACKGROUND Desmoplastic melanoma (DM) is a rare variant of malignant melanoma. A better understanding of the clinical course of DM will impact on its treatment. METHODS We reviewed the medical records of 59 patients with DM seen at the Mayo Clinics Scottsdale and Rochester since 1985. RESULTS Thirty-seven (63%) patients were male with a mean age of 62.8 years. The mean DM thickness was 6.5 mm. A total of 23 patients (39%) experienced local recurrence (LR). LR correlated with positive, unknown, or <1 cm margins. Fifty percent of patients who locally recurred subsequently developed metastatic disease. No patients were found to have positive nodal disease during ELND (16) or SLN biopsy (12). Only 1 patient (2%) developed delayed regional node metastases. Sixteen patients developed metastatic disease. The most common site was the lungs (81%). CONCLUSIONS LR is a significant problem and correlates with an increased risk of systemic metastatic disease. With the rare occurrence of lymphatic spread, we recommend patients undergo SLN biopsy only. DM appears to preferentially metastasize to the lungs and should be targeted when evaluating the patient for metastatic disease.

Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies.

Current pathologic criteria cannot reliably distinguish cutaneous anaplastic large cell lymphoma from other CD30-positive T-cell lymphoproliferative disorders (lymphomatoid papulosis, systemic anaplastic large cell lymphoma with skin involvement, and transformed mycosis fungoides). We previously reported IRF4 (interferon regulatory factor-4) translocations in cutaneous anaplastic large cell lymphomas. Here, we investigated the clinical utility of detecting IRF4 translocations in skin biopsies. We performed fluorescence in situ hybridization (FISH) for IRF4 in 204 biopsies involved by T-cell lymphoproliferative disorders from 182 patients at three institutions. In all, 9 of 45 (20%) cutaneous anaplastic large cell lymphomas and 1 of 32 (3%) cases of lymphomatoid papulosis with informative results demonstrated an IRF4 translocation. Remaining informative cases were negative for a translocation (7 systemic anaplastic large cell lymphomas; 44 cases of mycosis fungoides/Sézary syndrome (13 transformed); 24 peripheral T-cell lymphomas, not otherwise specified; 12 CD4-positive small/medium-sized pleomorphic T-cell lymphomas; 5 extranodal NK/T-cell lymphomas, nasal type; 4 gamma-delta T-cell lymphomas; and 5 other uncommon T-cell lymphoproliferative disorders). Among all cutaneous T-cell lymphoproliferative disorders, FISH for IRF4 had a specificity and positive predictive value for cutaneous anaplastic large cell lymphoma of 99 and 90%, respectively (P=0.00002, Fishers exact test). Among anaplastic large cell lymphomas, lymphomatoid papulosis, and transformed mycosis fungoides, specificity and positive predictive value were 98 and 90%, respectively (P=0.005). FISH abnormalities other than translocations and IRF4 protein expression were seen in 13 and 65% of cases, respectively, but were nonspecific with regard to T-cell lymphoproliferative disorder subtype. Our findings support the clinical utility of FISH for IRF4 in the differential diagnosis of T-cell lymphoproliferative disorders in skin biopsies, with detection of a translocation favoring cutaneous anaplastic large cell lymphoma. Like all FISH studies, IRF4 testing must be interpreted in the context of morphology, phenotype, and clinical features.

Primary cutaneous large cell lymphomas: morphologic, immunophenotypic, and clinical features of 20 cases

The morphologic, immunophenotypic, and clinical characteristics of 20 cases of primary cutaneous large cell lymphoma were analyzed. Immunoperoxidase stains in paraffin sections indicated B-cell phenotype in 14 cases and T-cell phenotype in six cases. By the Kiel classification, the B-cell lymphomas were classified into the following categories: follicular centroblastic (three patients), centroblastic/centrocytic with a predominance of large centrocytes (two patients), centroblastic (seven patients), and immunoblastic (two patients). The T-cell lymphomas (six cases) were all categorized as pleomorphic medium and large cell type. Three of these had an angiocentric growth pattern. The lymphocyte activation marker CD30 was expressed in three of the 20 cases. Among these 20 patients, the clinical course was remarkably variable. The only clinical or pathologic feature with prognostic significance was multicentricity of the skin lesions. All five patients with multifocal or disseminated skin lesions died within 13 months of their initial presentation; the median survival was 7 months. Most of the patients with localized skin lesions had an indolent clinical course with a median survival of 107 months. These results suggest that multicentricity of the skin lesions and necrosis are closely linked and are important prognostic features in cutaneous large cell lymphoma.

Clinical and histologic spectrum of human T-cell lymphotropic virus type I-associated lymphoma involving the skin

BACKGROUND Adult T-cell leukemia/lymphoma (ATL) is associated with infection with human T-cell lymphotropic virus type I (HTLV-I). OBJECTIVE The objective was to describe the clinical, histopathologic, and immunologic features in three patients with ATL involving the skin. METHODS Clinical histories and skin biopsy specimens were reviewed. Immunophenotypic studies were performed on peripheral blood lymphocytes (three patients) and on skin biopsy specimens (one patient). RESULTS Serologic testing in each patient was positive for HTLV-I. Specific cutaneous lesions of ATL were diverse. Histologic features included markedly epidermotropic lymphoid infiltrates and dermal aggregates of lymphocytes and macrophages resembling granulomas. One patient died 3 months after diagnosis; the other two are alive with residual lymphoma. CONCLUSION A spectrum of clinical, histologic, and immunophenotypic features are seen in ATL involving skin. Those cases with a chronic course may resemble mycosis fungoides clinically and histologically. Serologic testing for HTLV-I is recommended in all patients with cutaneous lymphoma from endemic areas and in those with other risk factors for HTLV-I infection.

Clinical and pathologic characteristics of disseminated cutaneous coccidioidomycosis

BACKGROUND Cutaneous lesions are a common manifestation of disseminated coccidioidomycosis, which has increasing prevalence in endemic regions. The clinical and histologic features may be more variable than is currently recognized. OBJECTIVE To characterize the clinical and histologic findings from a large series of disseminated coccidioidomycosis cases in the southwestern United States. METHODS Histologic materials and clinical records for all biopsy-positive cases (1975-2006) from three medical centers in Arizona were reviewed. RESULTS Patterns of inflammation were generally granulomatous, but the degree of organization, associated inflammatory milieu, density of tissue fungemia, and size of fungal spherules were highly variable. The clinical presentation was also inconsistent. LIMITATIONS The study only included cases with diagnostic histology. Records of clinical information were somewhat incomplete. CONCLUSION Clinical and pathologic findings in disseminated cutaneous coccidioidomycosis are variable and often subtle. A diagnosis requires a high degree of suspicion, especially in patients who reside in or have traveled through endemic regions.

Changing Surgical Therapy for Melanoma of the External Ear

Background: The purpose of this study was to evaluate the prognostic variables and clinical ramifications of melanoma of the ear.Methods: A retrospective chart review of patients treated since 1985 at the Mayo Clinic in Scottsdale, AZ, and Rochester, MN, identified 78 patients with complete follow-up.Results: Of these 78 patients, 68 (87%) were men; the mean age was 64 years (range, 23–87 years). Melanoma thickness averaged 1.7 mm (range, .2–7.0 mm). Treatment of the primary melanoma included wedge resection (59%), Mohs resection (14%), partial amputation (11%), skin and subcutaneous resection with perichondrium preservation (9%), and total amputation (7%). Nineteen patients underwent an elective lymph node dissection, and lymph node metastases were found in seven (37%). Two patients presented with clinically positive lymph nodes. Sentinel lymph node biopsy was performed in 10 patients. After a mean follow-up of 55.7 months, 10 patients (13%) had local recurrence, 9 patients (12%) had regional recurrence, and systemic metastases had developed in 17 patients (22%). Tumor thickness, lymph node metastases, and local recurrence significantly affected systemic recurrence.Conclusions: The treatment of malignant melanoma of the external ear should follow current standard guidelines, which require wide local excision with negative margins. Sentinel lymph node biopsy can be used to identify patients with lymph node metastases who are at high risk of recurrence.

The impact of biopsy technique on upstaging, residual disease, and outcome in cutaneous melanoma

BACKGROUND After skin biopsy of malignant melanoma, the findings in the subsequent wide local excision (WLE) sometimes result in upgrading of the T-category. Herein, we examine the influence of biopsy technique on residual disease in melanoma WLE specimens and on upstaging. METHODS We performed a retrospective review of data from malignant melanoma patients who underwent sentinel lymph node biopsy between 1997 and 2010. RESULTS A total of 609 patients were biopsied by shave (51%), punch (19%), and excision (30%). Residual disease was seen in 240 patients (39%) at WLE, of whom 60% had undergone shave biopsy. Fifty-nine patients had a T-category upgrade after WLE (10% of all patients); 64% were sampled by shave. Seven percent of patients with a T-category upgrade had negative margins initially. Positive biopsy margin and greater thickness predicted T-category upgrade. CONCLUSIONS Partial biopsy for melanoma resulted in more residual disease at WLE and a higher rate of T-category upgrade. Moreover, the presence of negative margins at biopsy did not ensure lack of residual disease.

Zosteriform skin metastases

A 66‐year‐old woman was referred for evaluation of a rash on the leg. She had a 1‐year history of stage IV bronchogenic adenocarcinoma with previous metastases to the right first metatarsal‐phalangeal (MTP) joint and a left supraclavicular lymph node. She underwent six cycles of chemotherapy with paclitaxel (Taxol; Bristol‐Myers Squibb Company, Princeton, NJ, USA) and carboplatin (Paraplatin; Bristol‐Myers Squibb Company, Princeton, NJ, USA) as well as palliative radiation therapy to the metastasis sites. One month after completing radiation therapy, the patient developed a nonpainful rash on the right thigh. This eruption was treated as a herpes zoster infection by her internist with 3 weeks of valcyclovir (Valtrex; Catalytica Pharmaceuticals, Greenville, NC, USA), but without improvement. One month later the leg became painful and swollen and the rash spread up the thigh to involve the groin and vulva. The patient was referred to the dermatology department. Physical examination revealed multiple red, indurated, crusted papules and nodules involving the medial, anterior, and lateral right thigh, labia majora, and suprapubic area. The lesions were grouped and arranged in a dermatomal zosteriform distribution ( Fig. 1 ). There was a visible peau d’orange appearance of the right leg with pitting edema. A punch biopsy showed irregular islands of atypical glandular epithelial cells infiltrating the superficial and deep dermis, consistent with metastatic adenocarcinoma ( Fig. 2a ). Immunohistochemistry showed positive staining to thyroid transcription factor (TTF) and cytokeratin 7 ( Fig. 2b and c ). The tissue did not stain with progesterone receptor, estrogen receptor, or gross cystic disease fluid protein (BRST‐2). This immunostaining pattern was identical to previous biopsies of the right first MTP joint and left supraclavicular lymph node metastases and is consistent with adenocarcinoma of the lung.

Collagenous fibroma (desmoplastic fibroblastoma)

Collagenous fibroma (desmoplastic fibroblastoma) is a recently described tumor that may arise in the subcutaneous tissue or skeletal muscle. We report a case of collagenous fibroma, occurring on the forehead of a 67-year-old man. An awareness of this entity is necessary to avoid confusion with other soft tissue neoplasms, especially extraabdominal fibromatosis.

Comparison of virtual microscopy and glass slide microscopy among dermatology residents during a simulated in-training examination

Virtual microscopy is increasingly being used in dermatopathology educational settings.