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Histiocytic hyperplasia with hemophagocytosis (HHH) is a relatively rare condition that has often been mistaken for a neoplastic disorder, but which most frequently represents a secondary reactive phenomenon whose associated risk factors have not yet been clearly defined. Histologic sections of hematopoietic organs (bone marrow, lymph nodes, and spleen) from 230 consecutive adults autopsies were reviewed to identify cases of HHH and to correlate them with clinical and autopsy findings. Moderate to severe HHH was present in the bone marrow in 102 and 230 cases, in the lymph nodes in 79 of 191 cases, and in the spleens of 16 of 209 cases. Recent blood transfusions, bacterial sepsis, major surgery, underlying disseminated malignancy, Candida sepsis, and viral infection were studied as potential risk factors. Both crude and adjusted analyses indicated a strong association between recent blood transfusions and the development of HHH in the bone marrow (P less than .0001). There was a marked dose-response relationship between number of units and the risk of HHH, with an adjusted risk ratio of 59.9 for five or more units compared with no transfusions. Bacterial sepsis was also associated with a significantly increased risk of HHH in the bone marrow in both the crude and adjusted analyses (adjusted risk ratio, 4.10; P = .0002). Major surgery and viral infection were only marginally associated with an increased risk for HHH (P = .03 and P = 0.06, respectively), and underlying disseminated malignancy and Candida sepsis did not appear to contribute any risk. Analyses for HHH in lymph nodes and spleen were similar to analysis for the bone marrow, but were somewhat less marked. The results of this study suggest that reactive HHH in hematopoietic organs may be far more common than has previously been acknowledged, and is most often multifactorial rather than related to a single underlying condition, with transfusions and bacterial sepsis constituting the most significant risk factors. Therefore, reactive HHH may represent a frequent secondary phenomenon in critically ill patients undergoing transfusions and should not be mistaken for an ominous sign or for the development of a superimposed malignancy.

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Richter's syndrome, the development of a malignant lymphoma in a patient with preexisting chronic lymphocytic leukemia (CLL) is an infrequent but well-documented phenomenon generally thought to represent a monoclonal proliferation of B-lymphocytes arising from the CLL. A heterogeneous population of cells consisting of sheets of transformed lymphocytes in combination with clusters of bizarre, atypical histiocytes developed in a patient with a history of longstanding CLL. Immunocytochemistry using a panel of monoclonal and polyclonal antibodies by immunoperoxidase techniques identified the presence of both B-lymphocytic and monocytic-histiocytic cell lines of differentiation. A mechanism of multiple differentiation is proposed to account for the dual cell population observed in this patient. Review of the literature appears to indicate that this phenomenon often may be involved in cases diagnosed as Richter's syndrome. The demonstration of cellular heterogeneity in the current case underscores the need for establishing a more precise definition for the histologic characterization of the terminal malignancy in Richter's syndrome.

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We report ten cases of a characteristic vesiculobullous eruption in patients with chronic lymphocytic leukemia. Clinically, six lesions were thought to represent insect bites. All ten patients had bone marrow examinations that confirmed the diagnosis of chronic lymphocytic leukemia. In six of ten patients serum protein and immunoelectrophoresis were performed. Six patients had immunoglobulin disturbances: one polyclonal IgG and IgM gammopathy, two monoclonal IgM gammopathies, two decreased levels of IgA, and one hypogammaglobulinemia. Direct and indirect immunofluorescence procedures were performed on two patients and results were negative. Immunoperoxidase procedures for IgG stained nonspecifically along torn/separated areas of the basement membrane in five patients. No immunohistochemistry was performed on the remaining three patients. The etiology and pathogenesis of these lesions are unknown. We favor the concept that they represent an unusual reaction to an arthropod bite, secondary to the underlying lymphoproliferative disorder. A second, and less likely theory, is that these lesions represent an unusual clinical presentation of bullous pemphigoid in patients with chronic lymphocytic leukemia.

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We report the case of a 66-year-old man with nodular lesions on the chest that were clinically diagnosed as epidermal cysts. Histologically the lesions consisted of fat necrosis with cystic spaces lined by striking membranous structures, mimicking a parasitic cuticle and exhibiting all the staining reactions of ceroid. Retrospective review of 33 consecutive cases of fat necrosis revealed similar membranous changes in 21% of the cases. The etiology and pathogenesis of this variant of fat necrosis are uncertain.

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This study represents the first two case reports of skin lesions positive for hepatitis B surface antigen (HBsAg) with the immunoperoxidase technique. A 25-year-old man and a 64-year-old woman with serologic evidence of acute B viral hepatitis and concurrent skin lesions are presented. Immunoperoxidase study of the skin lesions for HBsAg revealed strong positive staining of squamous epidermal cells, eccrine sweat glands, and endothelial cells in the superficial papillary dermis. Immunoperoxidase staining for hepatitis B core antigen (HBcAg) was negative in both cases. Electron microscopy failed to reveal viral particles.

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We have described a previously unreported lesion--peritoneal keratin globules in uterine adenosquamous carcinoma. We postulate that the keratin globules are derived from sloughed uterine adenosquamous carcinoma which gains access to the peritoneum through retrograde dissemination via the fallopian tubes, and we suggest that the finding of these globules does not alter the prognosis and staging of the primary carcinoma.

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A case of a malignant neoplasm with features suggestive of both malignant melanoma and squamous cell carcinoma is reported. The neoplastic cells were positive for both S-100 protein and keratin when stained by the indirect peroxidase-antiperoxidase method. The literature on other instances of bi- or multidirectional differentiation of neoplastic cells is reviewed. The significance of these findings for terminology of neoplasms is discussed.

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We have described a 25-year-old man with infestation of the feet by the burrowing flea Tunga penetrans, acquired in Brazil. We have also presented the microscopic characteristics of the flea and the histologic differential diagnosis.

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