Superficial and Deep Cutaneous Involvement by RAS-Associated Autoimmunne Leukoproliferative Disease (RALD Cutis): A Histologic Mimicker of Histiocytoid Sweet Syndrome.

RAS-associated autoimmune leukoproliferative disease (RALD) is a recently described noninfectious and nonmalignant clinical syndrome characterized by autoimmune disorders, massive splenomegaly, modest lymphadenopathy, and monocytosis. On the molecular level, RALD is defined by somatic mutations of either NRAS or KRAS gene in a subset of hematopoietic cells. To date, there is a dearth of well-documented histopathologic description of cutaneous involvement by RALD in the literature. In the current case report, a 43-year-old female patient with a history of RALD presented with clinical pictures of sepsis and an erythematous rash in the left lower extremity. Histologic examination revealed a dense perivascular and interstitial infiltrate of immature myeloid cells admixed with scattered neutrophils involving the dermis and subcutaneous adipose tissue, imparting a panniculitis-like histologic pictures. There was a strong angiocentric propensity of the immature hematopoietic cells as well as extensive extravasation of red blood cells, even in the subcutaneous adipose tissue. Immunohistochemically, the immature hematopoietic cells were positive for CD43, CD4, and CD68, but negative for CD34, CD117, and myeloperoxidase. Overall, the histologic and cytologic findings were highly reminiscent of histiocytoid Sweet syndrome. Review of the English literature revealed cutaneous involvements by RALD only in patients with KRAS mutation compared with none of its NRAS counterparts. However, larger clinicopathologic studies on cutaneous involvement by RALD are warranted. The term "RALD cutis" with its histologic and molecular features is suggested to serve as a potential groundwork for future studies of this rare phenomenon.

Phase II trial of individualized rituximab dosing for patients with CD20-positive lymphoproliferative disorders.

PURPOSE: To determine the feasibility and efficacy of pharmacokinetic (PK) -based maintenance dosing of rituximab and possibly design a more rational maintenance schedule. PATIENTS AND METHODS: Patients with CD20-positive lymphoproliferative disorders were treated with four weekly infusions of rituximab 375 mg/m(2). All patients without progressive disease were then monitored for 1 year and received a single infusion of 375 mg/m(2) when the level decreased below 25 microg/mL. RESULTS: Twenty-nine of 31 patients were assessable with a variety of histologic subtypes. The overall response rate (ORR) for the entire group was 59% with 27% complete responses (CRs) and 32% partial responses. The median PFS for all patients was 19 months, with a median follow-up of 25 months. In 22 patients with low-grade non-Hodgkin's lymphoma (LGNHL), the ORR was 63% with 36% CR and median progression-free survival (PFS) has not been reached. Of 29 assessable patients, 22 were available for PK-based maintenance. The median time to repeat bolus was 5 months (range, 1 to 9 months) for the first, 3.5 months (range, 2 to 5 months) for the second, and 3 months (range, 2 to 4 months) for the third infusion. Ninety-five percent of patients required three or fewer infusions to be maintained in the therapeutic range. CONCLUSION: Individualized PK dosing for rituximab produced efficacy comparable to other published maintenance strategies. PK data from this trial suggest that a rational maintenance strategy in patients with LGNHL would be a single dose of 375 mg/m(2) of rituximab every 3 to 4 months.