Catherine M. Stefanato

Survival Outcomes and Prognostic Factors in Mycosis Fungoides/Sézary Syndrome: Validation of the Revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer Staging Proposal

PURPOSE We have analyzed the outcome of mycosis fungoides (MF) and Sézary syndrome (SS) patients using the recent International Society for Cutaneous Lymphomas (ISCL)/European Organisation for Research and Treatment of Cancer (EORTC) revised staging proposal. PATIENTS AND METHODS Overall survival (OS), disease-specific survival (DSS), and risk of disease progression (RDP) were calculated for a cohort of 1,502 patients using univariate and multivariate models. RESULTS The mean age at diagnosis was 54 years, and 71% of patients presented with early-stage disease. Disease progression occurred in 34%, and 26% of patients died due to MF/SS. A significant difference in survival and progression was noted for patients with early-stage disease having patches alone (T1a/T2a) compared with those having patches and plaques (T1b/T2b). Univariate analysis established that (1) advanced skin and overall clinical stage, increased age, male sex, increased lactate dehydrogenase (LDH), and large-cell transformation were associated with reduced survival and increased RDP; (2) hypopigmented MF, MF with lymphomatoid papulosis, and poikilodermatous MF were associated with improved survival and reduced RDP; and (3) folliculotropic MF was associated with an increased RDP. Multivariate analysis established that (1) advanced skin (T) stage, the presence in peripheral blood of the tumor clone without Sézary cells (B0b), increased LDH, and folliculotropic MF were independent predictors of poor survival and increased RDP; (2) large-cell transformation and tumor distribution were independent predictors of increased RDP only; and (3) N, M, and B stages; age; male sex; and poikilodermatous MF were only significant for survival. CONCLUSION This study has validated the recently proposed ISCL/EORTC staging system and identified new prognostic factors.

Histopathology of alopecia: a clinicopathological approach to diagnosis

Stefanato C M
(2010) Histopathology56, 24–38
Histopathology of alopecia: a clinicopathological approach to diagnosis

Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin

Four mixed Merkel cell and squamous cell carcinomas of the skin are described. The patients ranged in age from 74 to 90 years and demonstrated or had a history of previous ultraviolet or infrared damage to the skin, manifested by basal cell carcinoma, squamous cell carcinoma, actinic keratoses, solar elastosis, and erythema ab igne. Light microscopic examination of all 4 cases revealed invasive neoplasms consisting of 2 distinct but admixed cell types. The predominant cell type was consistent with Merkel cell carcinoma and was characterized by scant cytoplasm, a small dark polygonal nucleus with granular chromatin, a high mitotic rate, and cytokeratin 20 positivity. In each case, the Merkel cell component merged with a cytokeratin 20 negative squamous component characterized by abundant eosinophilic cytoplasm, intercellular bridges, and keratinization with focal squamous pearl formation. Immunohistochemical staining patterns were consistent with the usual pattern for that cell type; transitional cells were not demonstrated. The intimate admixture of the 2 antigenically different neoplastic cell types, and common etiologic role of ultraviolet and possibly infrared damage, lend support to the theory that some Merkel cell carcinomas and squamous cell carcinomas may arise from a pluripotent epidermal stem cell.

Expanding the spectrum of frontal fibrosing alopecia: A unifying concept

BACKGROUND In frontal fibrosing alopecia (FFA), scalp alopecia dominates the clinical picture. However, eyebrow loss and hair loss in other body sites may also occur; this has been documented clinically, but rarely histopathologically. We describe the clinicopathological findings of 13 cases of FFA, with histopathologic data from the scalp, eyebrow, and body hair. METHODS Thirteen patients with a diagnosis of FFA, seen between 2006 and 2008, were included. Scalp biopsies were performed in all patients for histology and direct immunofluorescence (DIF). Biopsy specimens for histology were taken from the eyebrow in 6 patients and from the upper limb in 5 patients. RESULTS All 13 patients were female, 11 of whom were postmenopausal. The median age at onset of alopecia was 57 years. Clinical examination revealed a band of frontal hairline recession in all patients. Eyebrow loss was present clinically in all patients, with loss of body hair in 10 of 13. Histopathologic examination of the scalp, eyebrow, and upper limb skin biopsy specimens showed similar features, including a marked reduction in the number of hair follicles and a perifollicular lymphoid cell infiltrate with perifollicular fibrosis. Direct immunofluorescence was negative in all cases. LIMITATIONS Not all patients consented to biopsies of the eyebrows or upper limbs. CONCLUSION Eyebrow and peripheral body hair loss is not uncommon in FFA-a finding that is likely underreported. We have demonstrated that alopecia of the upper limbs in FFA is indeed common and, histopathologically, shows features of lichen planopilaris and scarring, similar to findings in the scalp and eyebrows. Consequently, the process of lichen planopilaris with scarring alopecia is generalized rather than localized only to the frontal scalp and eyebrows.

Scleromyxedema: A multicenter study of characteristics, comorbidities, course, and therapy in 30 patients

BACKGROUND Scleromyxedema is associated with a monoclonal gammopathy and other comorbidities. Its prognostic and therapeutic features are poorly documented because most reports deal with single cases or small series. OBJECTIVE We sought to describe the characteristics of patients with scleromyxedema regarding demographics, clinical characteristics, comorbidities, therapeutic interventions, and course. METHODS We conducted a retrospective and prospective multicenter study. RESULTS We identified 30 patients with scleromyxedema (17 men and 13 women). The mean age at diagnosis was 59 years. The mean delay between disease onset and diagnosis was 9 months. Monoclonal gammopathy was detected in 27 patients. Extracutaneous manifestations were present in 19 patients including neurologic (30%), rheumatologic (23.3%), and cardiac (20%) manifestations. Two patients developed hematologic malignancies. The most common therapies included oral steroids and intravenous immunoglobulins. Although corticosteroids were ineffective, intravenous immunoglobulins (alone or in combination with other drugs) induced complete remission in 4 and partial remission in 9 patients with a mean treatment duration of 2 years. In all, 21 patients were followed up for a mean period of 33.5 months, at which time 16 patients were alive, 12 with and 4 without skin disease. Five patients died: 2 with dermatoneuro syndrome and 1 each with myeloid leukemia, Hodgkin lymphoma, and myocardial insufficiency. LIMITATIONS This is mainly a retrospective study. CONCLUSIONS Our study confirms that scleromyxedema is a chronic and unpredictable disease with severe systemic manifestations leading to a guarded prognosis. There is no specific definitive treatment. Our data support the contention that intravenous immunoglobulin is a relatively effective and safe treatment. The response is not permanent and maintenance infusions are required.

Histologic and immunophenotypic features prior to transformation in patients with transformed cutaneous T-cell lymphoma : Is CD25 expression in skin biopsy samples predictive of large cell transformation in cutaneous T-cell lymphoma?

Large cell transformation (LCT) in cutaneous T-cell lymphoma (CTCL) is estimated to occur up to approximately 20% of patients. This morphologic change is associated with aggressive behavior and shortened survival. Our purpose was to identify morphologic and/or immunophenotypic features in CTCL skin biopsies that are predictive of transformation. We analyzed 12 cases of CTCL (three cases of mycosis fungoides and nine cases of Sezary syndrome) that underwent LCT and for which sequential biopsies before and after transformation were available. Eight of 12 cases had pre-LCT marker studies performed on frozen tissue. The histologic and immunophenotypic features of CTCL and LCT were reviewed. Morphologically, CTCL biopsies showed the following: Pautrier microabscesses (five cases), epidermotropism of single lymphoid cells (three cases), and nonspecific histology (four cases). Immunophenotyping prior to transformation showed aberrant loss of T-cell markers (CD5, CD7, CD5 and CD7) in three of eight cases. CD4:CD8 ratios were increased in all cases. Expression of CD25 by the neoplastic lymphoid cells was detected in six of seven cases. LCT immunophenotyping showed additional loss of CD7 in one of five cases and of CD25 in three of five cases. In conclusion, expression of CD25 in CTCL may identify a subset of patients at risk of undergoing LCT.

Cutaneous collagenous vasculopathy with generalized telangiectasia in two female patients

Cutaneous collagenous vasculopathy is characterized by generalized cutaneous telangiectasia and unique microscopic and ultrastructural vascular changes, consisting of marked collagen deposition within the vascular walls of the post-capillary venules in the superficial dermis. There are only 4 previous cases described in the medical literature, all in males, mostly middle-aged. We have recently seen two female patients with clinical and histopathologic features diagnostic of cutaneous collagenous vasculopathy, indicating that it is not restricted to males. As cutaneous collagenous vasculopathy can be clinically indistinguishable from generalized essential telangiectasia, and histopathologic studies are rarely performed for this condition, it is likely that cutaneous collagenous vasculopathy frequently passes unrecognized, but it may be more common than previously thought.

The histopathologic spectrum of regression in atypical fibroxanthoma

Background: Atypical fibroxanthoma (AFX) with prominent fibrosis, sclerosis and hyalinization, and near‐total tumor regression is rare.

A clinicopathological surprise: amelanotic malignant melanoma

A 58-year-old woman presented with a 20-year history of an asymptomatic, dry, scaly, erythematous, nonpigmented patch on the lateral aspect of her left upper arm. This had gradually increased in size, to its current dimensions of 26 · 32 mm (Fig. 1). The lesion was suggestive of Bowen s disease clinically, and an incisional skin biopsy was taken to confirm the diagnosis. Histologically, a lentiginous and junctional proliferation of moderately to severely atypical melanocytes with scattered pagetoid spread and a dense band-like infiltrate was observed, consistent with malignant melanoma in situ. Melan-A highlighted the melanoma in situ and absence of invasive disease. The lesion was therefore excised with 5 mm margins. Histological assessment of the excision specimen revealed a multifocal superficial spreading malignant melanoma, Breslow thickness 0.34 mm, Clark s level 2 (Fig. 2a) with a predominant in situ component, and with regression. Both the in situ and invasive components were confirmed with Melan-A (Fig. 2b). Re-excision with a further 5-mm margin was therefore performed and showed no evidence of residual melanoma. The term amelanotic melanoma is loosely used to describe both true amelanotic lesions which are devoid of pigment and melanomas with minimal residual pigmentation. The reported incidence of amelanotic melanoma varies from 1.8–8.1% of melanomas, but these figures include partially pigmented lesions. It is therefore difficult to ascertain the incidence of truly amelanotic melanoma. The majority of amelanotic melanomas reported are metastatic deposits, but of the primary lesions, in situ lentigo maligna, lentigo maligna melanoma and subungual lesions occur more commonly than other melanoma subtypes. Amelanotic superficial spreading melanoma is rare, with isolated case reports and one small series in the literature. Diagnosis of truly amelanotic lesions is difficult, especially if they present as scaly plaques resembling inflammatory dermatoses. Although dermoscopy may assist in the diagnosis of minimally pigmented lesions, it does not show proven efficacy with truly amelanotic lesions. Amelanotic lesions are frequently misdiagnosed, and in 63% of cases (44 ⁄ 70), mistreated before sampling for histological analysis. A review of our patient s lesion, even with the knowledge of the histological diagnosis, did not identify any clinical features suspicious of malignant melanoma. The gold-standard treatment for in situ melanoma is surgical excision using either Mohs micrographic surgery or taking 5-mm margins of clinically normal surrounding skin. In specific clinical scenarios, other PD

Recurrent erythema multiforme triggered by progesterone sensitivity.

Determining the underlying etiology of recurrent erythema multiforme (EM) can be a difficult endeavor. Although infection with herpes simplex virus (HSV) has been implicated in some cases, the precise trigger of a given patients recurrent EM often remains elusive. We discuss the case of a woman with a recurrent blistering eruption that was clinically and histopathologically consistent with EM. An investigation into the etiology of the patients EM suggested that HSV was not the causative factor but instead pointed toward a hormonal influence that we interpret as autoimmune progesterone dermatitis (APD). This case is presented to highlight the importance of considering hormonal triggers in women with recurrent EM that consistently flares during the luteal phase of the menstrual cycle, the point at which serum progesterone levels peak. A brief review of the literature regarding the diagnosis, histopathology, etiology and treatment of APD is further provided.