Introduction Atypical hemolytic uremic syndrome (aHUS) is a prototypic thrombotic microangiopathy attributable to complement dysregulation. In the absence of complement inhibition, progressive clinical deterioration occurs. We postulated that a biopsy of normal skin could corroborate the diagnosis of aHUS via the demonstration of vascular deposits of C5b-9. Materials and methods Biopsies of normal skin from 22 patients with and without aHUS were processed for routine light microscopy as well as immunofluorescent studies. An assessment was made for vascular C5b-9 deposition immunohistochemically and by immunofluorescence. The biopsies were obtained primarily from the forearm and or deltoid. Results Patients with classic features of atypical HUS showed insidious microvascular changes including loose luminal platelet thrombi except in two patients in whom a striking thrombogenic vasculopathy was apparent in biopsied digital ulcers. Extensive microvascular deposits of the membrane attack complex (MAC)/ C5b-9 were identified excluding one patient in whom eculizumab was initiated prior to biopsy. In 5 of the 7 patients where follow-up was available, the patients exhibited an excellent treatment response to eculizumab. Patients without diagnostic clinical features of atypical HUS failed to show significant vascular deposits of complement except two patients with TTP including one in whom a Factor H mutation was identified. Conclusion In a clinical setting where aHUS is an important diagnostic consideration, extensive microvascular deposition of C5b-9 supports the diagnosis of either aHUS or a subset of TTP patients with concomitant complement dysregulation; significant vascular C5b-9 deposition predicts clinical responsiveness to eculizumab.
Hypopigmentation in cutaneous T-cell lymphoproliferative disease should not always be equated with hypopigmented mycosis fungoides (MF). A form of hypopigmented pre-lymphomatous T-cell dyscrasia falling under the designation of the so-called hypopigmented interface variant of T-cell dyscrasia has recently been proposed. The aim of the present study was to establish hypopigmented interface T-cell dyscrasia as its own entity apart from other T-cell dyscrasias and MF using a patient case series. Twenty four cases of hypopigmented interface T-cell dyscrasia were identified in the dermatopathology database of Weill Medical College of Cornell University. There were 17 females and seven males (mean age, 36 years). In children and adolescents, the patients were most commonly of African American extraction. Truncal photo-protected areas manifesting as large solitary patches or multiple smaller macules were characteristic; disease progression to MF occurred in only one patient. The lesions responded to topical steroids and light therapy. The pathology was defined by a cell poor interface associated with degeneration of keratinocytes and melanocytes, and by lymphocytes whose nuclei showed low-grade cerebriform atypia, and which expressed a significant reduction in CD7 and CD62L expression. In 50% of the cases, the implicated cell type was of the CD8 subset. Clonality was not identified. Hypopigmented interface T-cell dyscrasia is a distinct entity separate from and rarely progressive to MF.
Intravascular lymphoma (IVL) is a rare and fatal disease, typically of B-cell origin. Most of the reported cases have been for primary IVL, and only a minority of cases are of recurrent IVL. In addition, recurrent IVL occurring after treatment of anaplastic large T-cell lymphoma (ALCL) by contrast is extraordinarily rare. In this article, we present 3 cases of recurrent cutaneous IVL (2 men and 1 woman) and compare these with 1 case of primary IVL. The patients ranged in age from 56 to 73 years and were encountered in the routine dermatopathology and consultative practices of one of the authors. In 2 of the cases, the patients had intravascular cutaneous ALCL. In regard to the remaining 2 patients, 1 patient had a recurrent intravascular cutaneous follicular lymphoma in the context of a history of diffuse large B-cell lymphoma. The fourth patient had a primary intravascular ALCL because there was no antecedent history. In all cases, the skin biopsies showed large aggregates of atypical cells within the blood vessels. Phenotypic studies revealed variable staining results with CD29 and CD54 in cases of recurrent IVL compared with those of primary IVL. Recurrent cutaneous IVL represents a somewhat heterogeneous group of lymphoproliferative disorders with a distinct variant being in the context of intravascular ALCL; the mechanisms of intravascular localization in recurrent IVL are likely different from those of primary IVL.
Key Clinical MessageIt's important to assess cases both clinically and pathologically for factors potentially predictive of an aggressive clinical course. We concluded that the relative immunosuppressive effects of PD1 may contribute to tumor progression while the lack of staining for cutaneous lymphocyte antigen may be an additional factor facilitating distant extracutaneous migration.
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