Kathy Foucar

Hantavirus pulmonary syndrome in the United States: A pathological description of a disease caused by a new agent

An outbreak of an acute respiratory disease in the southwestern United States has led to the recognition of a new hantaviral illness. This report describes a unique spectrum of antemortem and postmortem pathological findings seen in a case series of nine surviving patients and 13 who died. Clinical, laboratory, and autopsy findings were derived from a consecutive series of individuals confirmed to have hantavirus pulmonary syndrome. Laboratory studies included chemical, hematological, and bone marrow analyses as well as flow cytometric and immunohistochemical phenotyping. Autopsy tissues were examined by routine histological stains, immunohistochemical methods, and transmission electron microscopy. The lung is the primary target organ in this illness. Pulmonary abnormalities include pleural effusions, alveolar edema and fibrin, and an interstitial mononuclear cell infiltrate. Large immunoblast type cells are seen in the lungs, blood, bone marrow, lymph nodes, liver, and spleen. A tetrad of hematological findings includes left-shifted neutrophilic leukocytosis, thrombocytopenia, hemoconcentration in severe cases, and circulating immunoblasts. In contrast to previously described nephropathic hantaviral syndromes, hantavirus pulmonary syndrome is characterized by a unique constellation of pulmonary, hematological, and reticuloendothelial pathological findings. The pulmonary findings are distinguishable from fatal adult respiratory distress syndrome. The data suggest a capillary leak syndrome restricted to the pulmonary circulation. Likewise, the hematological picture is unique and may be valuable in the rapid identification of cases for further diagnostic studies.

Benign Hematogone-Rich Lymphoid Proliferations Can Be Distinguished From B-Lineage Acute Lymphoblastic Leukemia by Integration of Morphology, Immunophenotype, Adhesion Molecule Expression, and Architectural Features

Distinction of normal B-lymphoid proliferations including precursors known as hematogones from acute lymphoblastic leukemia (ALL) is critical for disease management. We present a multiparameter assessment of 27 bone marrow samples containing at least 25% hematogones (range, 25%-72%) by morphologic review. We used flow cytometry to evaluate B-cell differentiation antigen and adhesion molecule expression and immunohistochemistry on clot sections to evaluate architectural distribution. Flow cytometry revealed that intermediately differentiated cells (CD19+, CD10+) predominated, followed in frequency by CD20+, surface immunoglobulin-positive cells, with CD34+, terminal deoxynucleotidyl transferase (TdT)-positive cells as the smallest subset. Adhesion molecules (CD44, CD54) were expressed more heterogeneously compared with expression in acute lymphoblastic leukemia. Immunohistochemistry revealed that CD34+, TdT-positive cells were dispersed without significant clustering, while CD20+ cells exceeded CD34/TdT-positive cells in 24 of 25 cases. This multidisciplinary study demonstrates that hematogone-rich lymphoid proliferations exhibit a spectrum of B-lymphoid differentiation antigen expression with predominance of intermediate and mature B-lineage cells, heterogeneity of adhesion molecule expression, and nonclustered bone marrow architectural distribution.

U.S.-Canadian Consensus Recommendations on the Immunophenotypic Analysis of Hematologic Neoplasia by Flow Cytometry: Medical Indications

Bruce H. Davis,1* Kathy Foucar,2 Wlodek Szczarkowski,3 Edward Ball,4 Tom Witzig,5 Kenneth A. Foon,6 Denise Wells,7 Pat Kotylo,8 Rebecca Johnson,9 Curtis Hanson,5 and David Bessman10 1William Beaumont Hospital, Royal Oak, Michigan 2University of New Mexico, Albuquerque, New Mexico 3Cytometry Associates, Brentwood, Tennessee 4University of Pittsburgh, Pittsburgh, Pennsylvania 5Mayo Clinic, Rochester, Minnesota 6Markey Cancer Center, Lexington, Kentucky 7Hematologics, Seattle, Washington 8Indiana University, Indianapolis, Indiana 9Berkshire Medical Center, Pittsfield, Massachusetts 10University of Texas, Galveston, Texas

The histopathology of cutaneous lesions of Kikuchi's disease (necrotizing lymphadenitis): a report of five cases.

Kikuchis disease (KD) is an idiopathic, self-limited necrotizing lymphadenitis that can clinically and histologically mimic high-grade lymphoma, including Hodgkins disease, or can be mistaken for the lymphadenitis of systemic lupus erythematosus (SLE). Involvement of extranodal sites is unusual but well documented, especially in Asia, where KD is more common than in North America or Europe. The successful distinction of KD from malignant lymphoma and SLE is imperative for the appropriate treatment of affected patients. We describe five patients with cutaneous involvement by KD, all of whom presented with fever, lymphadenopathy, and an eruption on the skin of the upper body, which in one case was clinically suspected to be due to SLE and in another, polymorphous light eruption. The patients ranged in age from 10 months to 42 years (median, 33 years) and included three females and two males. All five patients had negative serologic studies for collagen vascular disease. Each patient had a lymph node biopsy showing the typical necrotizing lymphadenitis of KD. Skin biopsies from all five patients shared a specific constellation of histologic features: vacuolar interface change with necrotic keratinocytes, a dense lymphohistiocytic superficial and deep perivascular and interstitial infiltrate, varying amounts of papillary dermal edema, and abundant karyorrhectic debris with a conspicuous absence of neutrophils and a paucity of plasma cells, paralleling the nodal histology in KD. CD68 immunohistochemistry on paraffin-embedded sections showed many histiocytes and plasmacytoid monocytes in all cases, whereas CD3, CD4, and CD8 showed highly variable staining among the cases. There was only rare staining with TIA-1 and CD30. We believe that the papular eruption of KD has recognizable histopathologic features and that a CD68 stain that marks many cells that initially seem to be lymphocytes can be performed to confirm the diagnosis.

Cutaneous Waldenstrom macroglobulinemia in transformation

Waldenstrom macroglobulinemia is a low-grade B-cell lymphoproliferative disorder of the elderly with characteristic monoclonal IgM-producing neoplastic infiltrates of the bone marrow, lymph node, and spleen. Cutaneous manifestations are usually nonspecific such as purpura, ulcers, and urticarial lesions. These lesions are caused by hyperviscosity of the blood, immune complex-mediated vascular damage, paraprotein deposition, and amyloid deposition. Specific skin lesions occur rarely and generally consist of translucent, flesh-colored papules composed of monoclonal IgM deposits. Rarely, there may be violaceous lesions composed of low-grade lymphoplasmacytic infiltrates characteristic of Waldenstrom macroglobulinemia. Both cutaneous manifestations of the disease, as well as disease transformation to high-grade, large cell lymphoma are rare. We report two very unusual cases of Waldenstrom macroglobulinemia with documented skin disease that demonstrated transformation to high-grade lymphoma. Both patients were elderly men with long-standing Waldenstrom macroglobulinemia involving the bone marrow, who subsequently developed skin involvement by the disease. Waldenstrom macroglobulinemia can rarely manifest as cutaneous disease, sometimes as a high-grade transformation of low-grade Waldenstrom macroglobulinemia elsewhere. Distinction of cases of transformed Waldenstrom macroglobulinemia from de novo cutaneous large cell lymphoma may be important, because the two entities are likely biologically different.

Plasma cell dyscrasia: a case of POEMS syndrome with a unique dermatologic presentation.

POEMS (polyneuropathy, organomegaly [hepatosplenomegaly or lymphadenopathy], endocrinopathy, M protein, and skin changes) syndrome is an uncommon plasma cell dyscrasia with diverse manifestations, including lymphadenopathy as well as those that comprise the acronym. Dermatologic changes may include hyperpigmentation, thickened skin, hypertrichosis, and papular angiomas. These changes are believed to result from humoral products of the plasma cell clone and frequently resolve with treatment of the neoplasm. We describe a man with typical POEMS syndrome with a unique skin lesion: a large, sharply circumscribed, pigmented plaque on the anterior chest wall centered over a plasmacytoma of the sternum. Results of histologic examination showed a proliferation of capillaries of varying size, enlarged fibroblasts, and increased amounts of collagen and proteoglycan from the dermis to the periosteum. Because the outer cortex of the sternum was eroded, peptide mediators of vascular and fibroblast proliferation may have diffused directly from the plasma cell lesion into the tissues of the chest wall.

Atypical cutaneous lymphoproliferative disorder resembling mycosis fungoides in AIDS. Report of a case with concurrent Kaposi's sarcoma.

A variety of neoplastic disorders have been described in patients with AIDS. Kaposis sarcoma is the most common neoplasm and is recognized as one of the diagnostic criteria for AIDS. Unusual mucocutaneous carcinomas have also been reported in these patients, as have a variety of lymphoid neoplasms, including Hodgkins and non-Hodgkins lymphomas (NHLs). The NHLs that occur in AIDS patients are usually of B-cell or non-B, non-T-cell phenotype. In contrast, T-cell lymphomas have only rarely been reported in this patient population. We present the clinical, morphologic, and immunologic features of an atypical, cutaneous lymphoproliferative disorder resembling mycosis fungoides that developed in a 28-year-old homosexual man with AIDS and disseminated mucocutaneous Kaposis sarcoma.

A B-cell "chameleon": striking clinical, morphological, and immunophenotypic diversity of a single low-grade B cell clone.

A patient with an 18-year history of low-grade B-cell lymphoproliferative disorders is presented. Although the precise classification of these B-cell disorders was problematic, the blood, bone marrow, spleen, lymph node, and gastrointestinal lesions evaluated were compatible morphologically with such apparently disparate diagnoses as hairy cell leukemia, marginal zone lymphoma, mantle cell lymphoma, and gastrointestinal multiple lymphomatous polyposis. Although each low-grade disease that developed over an 18-year interval was clinically, morphologically, and immunophenotypically distinct, genotyping showed their derivation from a single B cell clone. This case emphasizes that a single B-cell clone may give rise to several distinct low-grade B-cell lymphoproliferative disorders with diverse clinical and pathological features.