Acneiform Presentations of Folliculotropic Mycosis Fungoides.

BACKGROUND: Folliculotropic mycosis fungoides (FMF) is a variant of cutaneous T-cell lymphoma that has clinical overlap with a variety of inflammatory follicular unit disorders. However, we describe distinctive presentations of FMF with acneiform features that can be diagnostically challenging, leading to diagnostic delay. OBJECTIVE: To highlight the importance of histopathologic and immunohistochemical evaluation for diagnostic confirmation of presumed inflammatory follicular unit-based disorders that are unusual in presentation or unresponsive to standard therapies. METHODS: A cross-sectional retrospective study of 5 consecutive patients with a histopathologic diagnosis of FMF was conducted. The clinical, histopathologic, immunophenotypic, and molecular genetic features of cases are presented. RESULTS: We describe 5 patients with clinical and histopathologic presentations of FMF masquerading as hidradenitis suppurativa, furunculosis, or acne vulgaris (age range 34-66 years, 4:1 female to male). Clinical morphologies included open and closed comedones, inflammatory pustules, papules and nodules, follicular papules with keratotic plugging, cysts, and scarring involving the face, trunk, and intertriginous areas. All patients failed to respond to standard therapies, including topical and oral antibiotics, topical and oral retinoids, or topical corticosteroids, before receiving the diagnosis of FMF. Lesional skin biopsies showed a perifollicular CD4-positive T-lymphocytic infiltrate with pilotropism, intrafollicular mucin deposition, foreign-body granulomatous inflammation, acute inflammation, and follicular epithelial necrosis. None had concurrent systemic mycosis fungoides. LIMITATIONS: Small retrospective cohort study. CONCLUSION: We present these cases to expand the clinical and histopathologic spectrum of FMF that may strikingly resemble acneiform disorders and to highlight the importance of diagnostic reconsideration with histopathologic evaluation.

Cutaneous peripheral T-cell lymphoma, not otherwise specified: A single-center prognostic analysis.

BACKGROUND: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a rare and aggressive disease either originating in or secondarily involving the skin. OBJECTIVE: We sought to assess clinical, histopathologic, and prognostic features of patients with cutaneous PTCL-NOS. METHODS: This was a retrospective chart review of patients with cutaneous PTCL-NOS between 1993 and 2013. RESULTS: Thirty patients with PTCL-NOS were included. Fourteen had skin-only disease and 15 had concurrent skin and systemic disease at presentation. In primary cutaneous PTCL-NOS, the overall survival rate at 5 years was 61% (95% confidence interval, 37-100%; number still at risk, 2). The median overall survival was 5.6 years. Patients were diagnosed a median of 2.4 months from symptom onset. Patients with concurrent disease died a median of 2.1 years after diagnosis. The estimated overall survival rate at 5 years after diagnosis was 29% (95% confidence interval, 13-67%; number at risk, 3). The median overall survival was 3.9 years. Patients were diagnosed a median of 6 months from symptom onset, with a 53% increased risk of death for each year from symptom onset to diagnosis. LIMITATIONS: This was a retrospective study with a limited number of cases. CONCLUSIONS: Age at diagnosis and B-symptoms predict poor survival in patients with cutaneous PTCL-NOS. In addition, poorer survival is observed in patients with multifocal lesions and concomitant skin and systemic PTCL-NOS.

Indolent course of cutaneous gamma-delta T-cell lymphoma.

Cutaneous gamma-delta T-cell lymphoma (γδTCL) is a rare malignancy that typically displays an aggressive clinical course. We present an unusual case of a 57-year-old woman with a 3-year history of lower extremity nodules. Histopathologic, immunophenotypic and molecular genetic studies revealed a clonal, predominantly pannicular gamma-delta T-cell infiltrate, leading to a diagnosis of cutaneous γδTCL. The clinical course was characterized by rapid improvement within months of starting systemic corticosteroids, with relapse in ulcerations but no new lesions more than 3 years after onset of disease. Our case and seven previously reported patients with indolent and relatively localized cutaneous γδTCL provide evidence that not all cases of this entity carry a poor prognosis. This indolent subset adds complexity to treatment of cutaneous γδTCL.

Retrospective analysis of tissue plasminogen activator as an adjuvant treatment for calciphylaxis.

OBJECTIVE: To report our experience with low-dose tissue plasminogen activator in the treatment of calciphylaxis, a rare, usually fatal thrombotic condition that results in ischemia, necrosis, and infarction of adipose and cutaneous tissue. DESIGN: Retrospective chart review. SETTING: Tertiary care academic medical center. PATIENTS: Fifteen patients (4 men and 11 women) with calciphylaxis, treated from January 1, 2002, through December 31, 2010. INTERVENTION: Treatment with tissue plasminogen activator, concomitant wound care, and management of calcium-phosphate status. MAIN OUTCOME MEASURES: Short-term ulcer healing, long-term survival. RESULTS: Patients received daily low-dose infusions of tissue plasminogen activator (mean treatment duration, 11 days). Six patients had no adverse reactions, 3 had minor bleeding, 6 required blood transfusions, and 3 had life-threatening bleeding. No patients died of treatment-related complications. Ten patients died (median time to death, 3.6 months; range, 23 days to 4.2 years). Of the remaining 5 patients, the median duration of follow-up was 36.8 months (range, 70 days to 4.3 years). Patients treated with tissue plasminogen activator had approximately 30% greater survival than controls, but the difference was not significant (P= .14). Our results were limited by the use of concomitant therapies, referral bias for advanced disease, and retrospective case-series design. CONCLUSIONS: Thrombolytic tissue plasminogen activator may be a useful adjunctive treatment in the management of patients with calciphylaxis. However, a multidisciplinary approach that includes aggressive wound care, débridement, thrombolytic therapy, restoration of tissue oxygenation, avoidance of infection, and control of calcium-phosphate homeostasis also is essential.

Unknown primary Merkel cell carcinoma: 23 new cases and a review.

BACKGROUND: Knowledge is limited regarding unknown primary Merkel cell carcinoma (UPMCC). OBJECTIVE: We sought to document the characteristics and behavior of UPMCC, and determine the most appropriate treatment. METHODS: A multicenter, retrospective, consecutive study reviewing patients given a diagnosis of UPMCC between 1981 and 2008 was completed. In addition, a literature review of cases of UPMCC was performed. RESULTS: In all, 23 patients with UPMCC are described and 34 cases from previous reports are compiled. Among the 23 new cases of UPMCC, the average age at diagnosis was 66.0 years; the majority of patients were male (87%) and Caucasian (100% of those reported). One patient was immunosuppressed, and 39% had a history of other cancer. After the initial biopsy, 16 patients had further evaluation of the involved lymph node basin. Half of these had additional positive nodes (8 of 16). The majority of patients had lymph node basin involvement only (78%), whereas 22% had lymph node basin and distant metastasis. The most common lymph node basin involved was inguinal. The median size of the involved lymph node at diagnosis was 5.0 cm. At 2 years, the overall survival of stage IIIB UPMCC was significantly improved versus stage IIIB known primary Merkel cell carcinoma (MCC): 76.9% to 36.4%. LIMITATIONS: Limited number of cases and retrospective review are limitations. CONCLUSION: Our data demonstrate improved overall survival in patients with stage IIIB UPMCC versus those with stage IIIB known primary MCC. Because of the unpredictable natural history of UPMCC, we recommend individualization of care based on the details of each patient's clinical presentation.

Prognostic factors in Merkel cell carcinoma: analysis of 240 cases.

BACKGROUND: Knowledge regarding behavior of and prognostic factors for Merkel cell carcinoma (MCC) is limited. OBJECTIVE: We sought to further understand the characteristics, behavior, prognostic factors, and optimal treatment of MCC. METHODS: A multicenter, retrospective, consecutive study of patients with known primary MCC was completed. Overall survival and survival free of locoregional recurrence were calculated and statistical analysis of characteristics and outcomes was performed. RESULTS: Among the 240 patients, the mean age at diagnosis was 70.1 years, 168 (70.0%) were male, and the majority was Caucasian. The most common location was head and neck (111, 46.3%). Immunosuppressed patients had significantly worse survival, with an overall 3-year survival of 43.4% compared with 68.1% in immunocompetent patients. In our study, patients with stage II disease had improved overall survival versus those with stage I disease, in a statistically significant manner. Patients with stage III disease had significantly worse survival compared with stage I and with stage II. Primary tumor size did not predict nodal involvement. CONCLUSION: The data presented represent one of the largest series of primary MCC in the literature and confirm that MCC of all sizes has metastatic potential, supporting sentinel lymph node biopsy for all primary MCC. Because of the unpredictable natural history of MCC, we recommend individualization of care based on the details of each patient's tumor and clinical presentation.

Net-like pattern of calcification on plain soft-tissue radiographs in patients with calciphylaxis.

BACKGROUND: Calciphylaxis is a rare, life-threatening syndrome marked by vascular calcification and cutaneous necrosis. The role of radiographic imaging in assisting in diagnosis has not been established. OBJECTIVE: To investigate the potential role of plain radiographic imaging in the diagnosis of calciphylaxis. METHODS: We searched for cases of patients at our tertiary referral center with a diagnosis of calciphylaxis between Jan 1, 1996, and Dec 31, 2010. Two control patients receiving dialysis but without calciphylaxis were age- and sex-matched to each study patient. Plain radiographs were obtained from the date closest to diagnosis in patients with calciphylaxis and from matched controls at approximately the same dates. Two radiologists, masked as to cases and controls, read each image together. Size of calcified vessels, pattern and extent of calcifications, presence of net-like or other calcifications, and bone density/mineralization were recorded and analyzed. RESULTS: Twenty-nine patients with calciphylaxis (mean age, 57 years; 21 [72%] women) were identified. Mean age at diagnosis was 57 years (range, 36-75 years). Compared with those of controls, plain radiographs of patients with calciphylaxis had more vascular calcifications, more small-vessel calcifications, and a netlike pattern of calcifications. A netlike pattern of calcifications had considerable strength of association with calciphylaxis (odds ratio, 9.4) and a specificity of nearly 90%. These findings were preserved even if only one image was used per patient. LIMITATIONS: This was a retrospective study. CONCLUSION: A netlike pattern of calcifications on plain radiographs was more common in patients with calciphylaxis and may aid in diagnosis.

The dermatology hospitalist: creating value by rapid clinical pathologic correlation in a patient-centered care model.

BACKGROUND: The active and continuous presence of dermatologists in hospitals has undergone continued involution over the past two decades. Our patient-centered, value-based dermatology hospitalist model describes an efficient system for the integration of the dermatologist in the hospital treatment team. METHODS: We describe five difficult inpatient cases to illustrate the value of dermatology intervention and clinical pathologic correlation in facilitating timely diagnosis and treatment. RESULTS: Prompt specialty evaluation and clinicopathologic correlation by hospital dermatologists led to decreased morbidity and the avoidance of delay in initiating definitive treatment. CONCLUSIONS: Efficient evaluation and clinicopathologic correlation by dermatology hospitalists are essential to hospitals that provide comprehensive care. This value-based model has the potential to produce better patient outcomes and greater satisfaction in both patients and other health care providers.

The role of CD10 in distinguishing atypical fibroxanthoma from sarcomatoid (spindle cell) squamous cell carcinoma.

BACKGROUND: The role of CD10 needs clarification in a broader immunohistochemical battery for distinguishing atypical fibroxanthoma (AFX) from spindle cell squamous cell carcinoma (sSCC). METHODS: We retrospectively reviewed 23 cutaneous spindle cell tumors previously classified as AFX (n = 11) or as sSCC (n = 12). Each tumor was stained with CD10, S-100, p63 and two or more cytokeratin stains. Defining AFX as a diagnosis of exclusion based on multiple negative cytokeratin stains and negative p63 staining, we reclassified four squamous cell carcinomas (SCCs) as AFX. CD10 staining was reviewed and graded in all tumors. RESULTS: Fifteen tumors were classified as AFX. Strongly positive CD10 staining was observed in all 15 AFXs, as well as four (50%) of the eight SCCs. Expression of p63 was seen in six sSCCs (75%). CONCLUSIONS: CD10 is consistently expressed by AFX. However, CD10 is also often strongly expressed by sSCC. Positive staining with p63 favors a diagnosis of sSCC. An immunohistochemical battery useful for distinguishing AFX from sSCC may include CD10, p63 and two cytokeratin markers. However, CD10 alone should not be relied upon in the distinction of these entities.

Malignant melanoma in solid transplant recipients: collection of database cases and comparison with surveillance, epidemiology, and end results data for outcome analysis.

OBJECTIVE: To determine malignant melanoma cause-specific and overall survival among patients with melanoma diagnosed after organ transplantation compared with a national sample with malignant melanoma. DESIGN: Retrospective review. SETTING: Mayo Clinic sites. PATIENTS: Immunosuppressed organ transplant recipients with malignant melanoma identified from surgical and medical databases at Mayo Clinic (1978-2007), the Organ Procurement and Transplantation Network/United Network for Organ Sharing database (1999-2006), and the Israel Penn International Transplant Tumor Registry (1967-2007). MAIN OUTCOME MEASURES: Prognostic analyses by Breslow thickness and Clark level of overall and melanoma cause-specific survival. Expected survival rates were estimated by applying the age-, sex-, and calendar year-specific survival rates of patients with malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program to the study cohort. RESULTS: Malignant melanoma was diagnosed in 638 patients (724 cases) after transplantation. Breslow thickness was available for 123 patients; Clark level, for 175. Three-year overall survival rates for patients stratified by Breslow thickness (≤ 0.75, 0.76-1.50, 1.51-3.00, and >3.00 mm) were 88.2%, 80.8%, 51.2%, and 55.3%, respectively, and 3-year cause-specific survival rates (95% confidence intervals) were 97.8% (93.7%-100%), 89.4% (76.5%-100%), 73.2% (53.2%-100%), and 73.9% (56.4%-96.6%), respectively. Three-year cause-specific survival rates (95% confidence intervals) for patients stratified by Clark level (I-IV) were 100%, 97.4% (92.4%-100%), 82.8% (65.3%-100%), and 65.8% (51.8%-83.7%), respectively. For patients with Breslow thickness of 1.51 to 3.00 mm and Clark level III or IV, the cause-specific survival rate in the study sample was significantly different from the expected estimates for patients with the same Breslow thickness or Clark level. CONCLUSIONS: Compared with the expected survival rates derived from malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program, immunosuppressed organ transplant recipients with thicker melanomas (ie, with a Clark level of III or IV or a Breslow thickness of 1.51 to 3.00 mm) had a significantly poorer malignant melanoma cause-specific survival rate. The overall survival rate was worse among patients with a prior history of transplantation, regardless of Breslow thickness or Clark level.

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, Fisher's 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.

Folliculotropic mycosis fungoides: single-center study and systematic review.

OBJECTIVES: To clarify clinicopathologic features and reconcile discrepancies in previous studies of folliculotropic mycosis fungoides (FMF). DESIGN: A single-center retrospective clinicopathologic study and a systematic review of FMF. SETTING: Tertiary referral center in the midwestern United States. PATIENTS: Patients with clinical and histopathologic evidence of FMF seen at the tertiary referral center during a 12(1/2)-year period. MAIN OUTCOME MEASURES: Clinicopathologic features of FMF. RESULTS: Fifty patients (32 male [64%] and 18 female [36%]) met study criteria for the clinicopathologic review. Pruritic patches, plaques, and folliculocentric lesions (milia, cysts, and alopecia) on the head, neck, and trunk were common clinical findings. The mean time to diagnosis of FMF was 5.0 years. Diagnostic latency did not affect risk of death. One-year and 5-year overall survival rates were 96% and 62%, respectively. Frequent microscopic features were follicular mucinosis (74%) and epidermotropism (54%). Systematic review of 186 additional patients confirmed male predominance (ratio of men to women, 3.2:1.0), prevalent pruritus (73%), frequent follicular mucinosis (69%) and epidermotropism (37%) microscopically, and common head, neck, and trunk involvement. Combined data demonstrated that 6% of patients with FMF had concurrent non-mycosis fungoides hematologic malignant neoplasms and that the 5-year overall survival rate was 62% to 64%. CONCLUSION: Folliculotropic mycosis fungoides has distinct clinical and microscopic features and is associated with a poor 5-year overall survival rate.

Effects of chronic lymphocytic leukemia on the development and progression of malignant melanoma.

BACKGROUND: An association exists between chronic lymphocytic leukemia and malignant melanoma. OBJECTIVES: To study the clinical behavior of malignant melanoma in patients with chronic lymphocytic leukemia. METHODS: A retrospective chart review was conducted of patients with chronic lymphocytic leukemia and malignant melanoma. RESULTS: Sixty-nine patients had malignant melanoma and chronic lymphocytic leukemia. The recurrence-free and metastasis-free survival rates at 2, 5, and 10 years were 93.4% and 89.1%, 83.8% and 93.4%, and 87.4% and 82.1%, respectively. No significant difference was observed in age- and sex-adjusted mortality rates between patients with chronic lymphocytic leukemia diagnosed before malignant melanoma and those with chronic lymphocytic leukemia diagnosed after malignant melanoma. LIMITATIONS: Retrospective study and small patient population. CONCLUSION: Patients with malignant melanoma and chronic lymphocytic leukemia were not shown to have worse survival rates than those with stage IA, IB, and IIA disease. Further research and prospective study are needed.

Paucity of intraepidermal FoxP3-positive T cells in cutaneous T-cell lymphoma in contrast with spongiotic and lichenoid dermatitis.

BACKGROUND: FoxP3 is the most specific available marker for regulatory T cells (Tregs). Tumor-associated FoxP3-positive Tregs have been identified in various neoplasms, including cutaneous T-cell lymphoma (CTCL). FoxP3 expression in CTCL varies across groups; few studies have compared CTCL with inflammatory conditions. METHODS: Lesional skin biopsies from 20 patients with CTCL [13 mycosis fungoides (MF); 7 Sézary syndrome (SS)] and 22 with inflammatory dermatoses (11 spongiotic; 11 lichenoid or interface) were examined for FoxP3 expression by immunohistochemistry. Epidermal FoxP3-positive lymphocytes were counted as a percentage of the total epidermal CD3-positive T-cell population. RESULTS: FoxP3-positive T cells composed the minority of infiltrate in all major categories. Lower numbers of epidermal FoxP3-positive T cells were observed in CTCL, particularly MF, than in inflammatory dermatoses (P < .001). CTCL neoplastic T cells did not express FoxP3. CONCLUSION: FoxP3-positive T cells are less frequently encountered in MF than in inflammatory dermatoses. FoxP3-positive T cells occur in higher proportions in the dermis than in the epidermis and probably correlate with coexisting inflammatory components. CTCL neoplastic cells do not typically express a Treg phenotype and are associated with low numbers of FoxP3-positive Tregs in the infiltrate. FoxP3 expression by immunohistochemistry may aid histologic evaluation of these conditions.

Fatal cytotoxic cutaneous lymphoma presenting as ulcerative psoriasis.

BACKGROUND: Psoriasis is a common, nonulcerative skin disorder. OBSERVATIONS: We describe 3 men recently referred to our institution for evaluation and treatment of severe, ulcerative psoriasis that ultimately was determined to be aggressive, cytotoxic, cutaneous lymphoma. Each had a history of relatively indolent, nonulcerative patches and plaques (duration, 2-45 years) that changed to ulcerated lesions; these rapidly progressed and eventuated in death. CONCLUSIONS: The clinical characteristics of the skin lesions and the histopathologic findings form a distinct and rare presentation of cutaneous lymphoma. The initial course is similar to that of mycosis fungoides but eventuates in a highly aggressive disease with fatal outcome.

Outcomes of melanoma in recipients of solid organ transplant.

BACKGROUND: There is concern that the immunologic tumor malignant melanoma (MM) may have worse outcomes in immunosuppressed hosts than in the general population. OBJECTIVE: We sought to describe outcomes of MM in immunosuppressed solid organ transplant recipients and compare them with the general population. METHODS: We conducted a retrospective review of medical charts and pathology slides of cases of MM and solid organ transplantation between 1978 and 2007, with comparison of outcomes. RESULTS: In all, 48 MMs were identified in 43 transplant recipients. No patient with MM before transplant receipt had melanoma recurrence, subsequent metastasis, or death caused by melanoma. Of patients with MM diagnosed after transplantation, metastases developed in 3 patients, and two patients died of melanoma. LIMITATIONS: Retrospective review and low number of cases are limitations. CONCLUSIONS: Outcomes of MM in immunosuppressed transplant recipients appeared similar to those in prognostically matched nonimmunosuppressed hosts. The small number of cases limited statistical comparisons.