Kaposi's sarcoma in women: A clinicopathologic study.

BACKGROUND: Although all epidemiologic subsets of Kaposi's sarcoma (KS) (i.e., sporadic, endemic, epidemic, and iatrogenic) have an association with human herpes virus 8 (HHV8), these subsets occur in patient populations with distinctive clinical features. To a variable degree men outnumber women in all subsets. OBJECTIVE: A retrospective study of women with histologically proven cutaneous KS was undertaken to determine the clinical and histopathologic features, as well as any associations. METHODS: Two hundred and fifty cases of cutaneous KS in women from 1975 to 1993 were reviewed. RESULTS: Of the patients, 80% were more than 60 years of age, and of the patients less than 60 years old, 28 were from areas of the world with endemic KS. All HIV+ patients but one were from areas of endemic KS. Two patients were renal transplant patients. Sixty-four percent of the patients had single lesions and 21% recurrent lesions. Twelve patients had, or were known to develop, internal involvement, and in six patients the cause of death was KS. All but four cases histologically showed areas of solid proliferations of tumour cells consistent with plaque or tumour stage. An angiosarcoma-like histologic pattern appeared to be associated with more aggressive epidemiologic subsets. High mitotic rates were rarely seen and did not correlate with aggressive epidemiologic subsets. CONCLUSION: Kaposi's sarcoma in women is diagnosed almost exclusively in plaque or tumour stage. The majority of women within our study fit within the epidemiologic subset of sporadic KS.

Lymphoid markers, activation markers, and adhesion molecules in cutaneous biopsy specimens from HIV+ patients with disease progression. The Military Medical Consortium for the Advancement of Retroviral Research.

BACKGROUND: One important factor in understanding the pathogenesis of human immune deficiency virus (HIV) disease is documenting the patterns of immune dysregulation present in HIV-positive patients. The cells which home to skin are mainly certain subsets of T cells and, as opposed to the peripheral blood, where circulating factors may inhibit terminal phenotypic differentiation, the cutaneous environment potentiates differentiation during cutaneous eruptions. OBJECTIVE: The authors' aim was to characterize the inflammatory dermatoses in biopsy specimens from HIV-positive patients with immunohistochemical stains for lymphoid markers, activation markers, and adhesion molecules and to determine if there was any correlation with the type of dermatosis and the HIV-disease stage. METHODS: Lymphoid and activation markers as well as adhesion molecules were studied on cutaneous biopsy specimens from 96 inflammatory dermatoses in HIV-positive patients. The dermatoses included psoriasiform dermatoses with and without a lichenoid component, perivascular lymphoid dermatoses, perivascular and periadnexal inflammatory dermatoses, spongiotic dermatoses, granulomatous dermatoses, and neutrophilic dermatoses with and without vasculitis. RESULTS: Although there was a decrease in CD4/CD8 ratios in the cutaneous inflammatory dermatoses with progression of the disease, the ratios of CD4/CD8 cells were far higher than those in the peripheral blood. There were also increasing numbers of CD23+ cells and increased E-Selectin expression on endothelial cells from the early stages of disease, with no consistent pattern of ICAM-1 expression on epithelial cells with disease progression. CONCLUSIONS: The expression of lymphoid markers, activation markers, and adhesion molecules in the skin with progression of HIV disease, is consistent with a T helper (Th)1 to Th0/Th2 cytokine pattern of immune dysregulation. This cytokine pattern may be modified by the cytopathic effects of HIV on lymphoid and dendritic populations and by effects of other concurrent infections. Significant numbers of CD4+ T cells in skin infiltrates, with low peripheral CD4 T-cell counts, suggest that the cutaneous T-cell populations may be distinctive.

Histopathologic features seen in cutaneous photoeruptions in HIV-positive patients. Military Medical Consortium for the Advancement of Retroviral Research (MMCARR).

BACKGROUND: There have been scattered reports of HIV+ patients with increased reactions to light as well as anecdotal reports of HIV+ patients with increased morbidity secondary to radiation therapy. METHODS: As a part of a military study of HIV+ patients, we followed 987 patients for cutaneous disease for 4 years. All patients were questioned on a periodic basis about increased sensitivity to light. These patients received a physical examination at each protocol visit, and they were given the opportunity to receive all their dermatologic care within the HIV clinic. Fourteen of the patients with photo-induced eruptions were evaluated clinically at the time of the eruption, and 11 of these were biopsied. RESULTS: Thirty-three of the patients reported photo-induced reactions unrelated to oral medications. Although sensitivity to light often began in the early stages of HIV disease, reactions became more severe and more chronic with disease progression. Histologic features varied from few to numerous apoptotic/necrotic keratinocytes within the mid to upper levels of the epidermis associated with a perivascular inflammatory infiltrate, to apoptotic/necrotic keratinocytes throughout an acanthotic epidermis with a lichenoid/interface infiltrate. CONCLUSIONS: Although the pathogenesis of these light reactions is not known, these reactions may be related to depletion of endogenous scavengers which results in increased oxidative stress and is modulated by the pattern of immune dysregulation and metabolic dysregulation induced by HIV disease.

Bacillary angiomatosis in an immunocompetent child.

Bacillary angiomatosis (BA) is a pathological process characterized by prominent vascular proliferation secondary to organisms of the genus Rochalimaea. BA has been most commonly associated with HIV-1+ patients, but has also been reported rarely in other immune-suppressed patients and in a small group of patients with no demonstrated immune suppression. Even in immune-suppressed children, BA is extremely rare. We report a 5-year-old girl with no apparent immune suppression and no risk factors for HIV-1+ disease, who presented with a skin lesion that histopathologically was diagnostic of BA.

Bacillus piliformis infection (Tyzzer's disease) in a patient infected with HIV-1: confirmation with 16S ribosomal RNA sequence analysis.

Bacillus piliformis is a long, rod-shaped bacterium that has never been grown in cell-free medium and whose taxonomic classification is uncertain. B. piliformis is the causative agent of Tyzzer's disease, which is frequently reported in laboratory, wild, and domesticated animals. The spectrum and severity of this disease is wide in animals. Although many infections are rapidly fatal, subclinical infections are also common. To date, there have been no reports of B. piliformis infection in human beings, although elevated antibody levels have been reported in pregnant women. We describe the first case of human B. piliformis infection, in a man with HIV-1 infection and chronic, localized, crusted verrucous lesions. The diagnosis was confirmed by ribosomal RNA sequencing. The spectrum of organisms leading to infection and the spectrum of diseases caused by these organisms continue to expand, as new infections are identified and as patients with HIV-1 live longer with more severe immune suppression. The extreme difficulty in culturing B. piliformis and the lack of clinical and histopathologic experience with this organism in human beings mean that B. piliformis is potentially another infectious agent to be considered in human beings. Also, when an infectious organism is a strong clinical consideration, silver stains may be of use when results of routine bacterial staining are negative.

Clinical and histopathologic features of hair loss in patients with HIV-1 infection.

BACKGROUND: Hair loss is common in patients with HIV-1 infection, and in black patients this loss may be associated with straightening. Possible causes are frequently present in patients with HIV-1. These causes include chronic HIV-1 infection itself and recurrent secondary infections, nutritional deficiencies, immunologic and endocrine dysregulation, and exposure to multiple drugs. However, histopathologic features have rarely been reported in these patients. OBJECTIVE: The objective was to evaluate the changes in the hairs of a group of these patients and to identify the light microscopic and ultrastructural changes in the hairs and the histologic changes in the scalp. METHODS: Hair plucks and pulls with scanning electron microscopy of the hairs were done on 10 patients with late-stage HIV-1 infection. In addition, scalp biopsy specimens were examined in both vertical and transverse sections. RESULTS: All patients had telogen effluvium. Numerous apoptotic or necrotic keratinocytes were seen in the upper external root sheath follicular epithelium in addition to a mild to moderate perifollicular mononuclear cell infiltrate often containing eosinophils. Variable dystrophy of the hair shafts was also a consistent feature. CONCLUSION: Although telogen effluvium is a common response to a wide spectrum of biologic stresses, the presence of apoptotic or necrotic keratinocytes within the upper end of the external root sheath epithelium and dystrophy of hairs may be markers of hair loss in patients with HIV-1 infection.

Decreased CD7 expression in cutaneous infiltrates of HIV-1+ patients. Military Medical Consortium for the Advancement of Retroviral Research (MMCARR).

CD7 is an early T-cell marker that has been used in the diagnosis of stem cell leukemias. Loss of expression of CD7 with a battery of other mature T-cell markers has also been used as one criteria in the diagnosis cutaneous T-cell lymphomas. More recently, CD7-negative T cells have been shown to be a normal population of T cells in the peripheral blood and the skin, and may represent a mature T-cell population with a different pattern of maturation and activation. In addition, in HIV-1 disease expansion of CD7-negative T cells has been found in the peripheral blood. We evaluated the number of CD7-negative T cells in skin infiltrates to determine whether there was an increase of CD7-negative T cells. We studied T-cell markers including CD3, CD4, CD7, CD8, CD20, CD29, and HLA-DR on cutaneous biopsy material from inflammatory dermatoses in 57 patients with HIV-1 disease in Walter Reed stages (WR) 1-6, and in 14 HIV-1-negative patients WR0. The inflammatory infiltrates showed a moderate to marked decrease in CD7 expression on CD3+ T cells in benign inflammatory infiltrates of the majority of HIV-1+ patients. The majority of HIV-1-negative patients showed no decrease in CD7 expression, although 5 of 14 showed a moderate decrease and 1 of 14 showed a marked decrease. Although the nature of CD7- T cells has not been clearly defined, this population of mature T cells appears to have distinct immunologic properties as well as a trophism for skin. Better characterization of these T cells, as well as factors that promote their maturation and activation, may give clues to the high incidence as well as the pathogenesis of skin disease in HIV-1+ patients.

Changes of verruciform xanthoma in an HIV-1+ patient with diffuse psoriasiform skin disease.

Verruciform xanthoma occurs most commonly in the oral mucosa; however, rare cutaneous lesions have been described. Although the pathogenesis of this entity is not known, dysregulation of epithelial proliferation and degenerative changes in the epithelium may explain the occurrence of this lesion in association with inflammatory dermatoses, epithelial hamartomas, and epithelial dysplasia. We report an HIV-1+ patient with diffuse psoriasiform skin lesions that showed histologic changes of verruciform xanthoma.

Melanocytic activation in HIV-1 disease: HMB-45 staining in common acquired nevi. Military Medical Consortium for the Advancement of Retroviral Research.

BACKGROUND: An increase in pigmented lesions has been reported in HIV-1-infected patients. In a study of HIV-1-positive patients, we have seen patients who noticed new or changing pigmented lesions. OBJECTIVE: The goal of this study was to determine to what degree these pigmented lesions showed evidence of significant melanocytic proliferation as opposed to increased pigment production without significant melanocytic proliferation. METHODS: Biopsy specimens were studied with routine light microscopy and immunohistochemical stains including S-100 protein, HMB-45, and proliferating cell nuclear antigen. RESULTS: The lesions included two malignant melanomas and 42 benign melanocytic lesions. Significant staining of dermal melanocytes with HMB-45 was present in two of three melanomas and in 19 of 42 nevi. With stains for proliferating cell nuclear antigen there was a positive reaction in the dermal component of both melanomas and a negative reaction in the dermal cells of the nevi. CONCLUSION: In some HIV-1-infected patients there is stimulation of melanosome production without significant melanocyte proliferation.

A clinical and pathological comparison of the WHO and CDC case definitions for AIDS in Kinshasa, Zaïre: is passive surveillance valid?

OBJECTIVES: To compare the specificity of the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) case definitions for AIDS in autopsy cases from Zaïre. SETTING: Mama Yemo Hospital and University Hospital morgues in Kinshasa, and Karawa Hospital in Equateur Region, Zaïre. METHODS: Autopsy cases with a clinical diagnosis of AIDS on the death certificate or chart were studied. Evaluation included post-mortem HIV-1 serology, chart review for specific AIDS-related symptoms and signs, and application of WHO and CDC case criteria to the clinical and autopsy diagnoses. RESULTS: Of the 68 diagnosed AIDS cases, 98% fulfilled WHO criteria for AIDS and 93% fulfilled both WHO and CDC criteria. All cases fulfilling both criteria were HIV-1-seropositive. Opportunistic infections accounted for 84% of CDC AIDS-defining conditions. Disseminated tuberculosis was the most frequent (41%) specific diagnosis; Pneumocystis carinii pneumonia was rare (< 2%). CONCLUSIONS: There was good concordance between WHO and CDC case definitions. A diagnosis of AIDS on the chart or death certificate is adequate for surveillance purposes in this population.

Granulomatous Pneumocystis carinii in AIDS patients.

Seven cases of Pneumocystis carinii pneumonia with granulomatous reaction in patients infected with the human immunodeficiency virus are described. The patients were all adult men between the ages of 32 and 45 years, with different high-risk factors. Clinically, all the patients presented with a history of non-productive cough and shortness of breath. Two of the patients had a past history of pulmonary pneumocystosis. Radiologically, six patients had diffuse pulmonary infiltrates and one nodular pulmonary infiltrate. Transbronchial lung biopsies were obtained in four patients and open lung biopsies in three. All presented a predominant granulomatous reaction composed of epithelioid and multinucleated giant cells. Several other special stains to detect the presence of other microorganisms to account for the granulomatous reaction were negative.

Cutaneous neoplasms in a military population of HIV-1-positive patients. Military Medical Consortium for the Advancement of Retroviral Research.

BACKGROUND: In HIV-1-positive patients there have been no prospective studies that show an increase in cutaneous neoplasms. OBJECTIVE: We observed HIV-1-positive patients to determine whether or not there was an increased incidence of cutaneous malignancies. METHODS: A total of 724 HIV-1-positive patients were examined during a 36-month period for the development of cutaneous malignancies. RESULTS: The most common cutaneous neoplasm found was Kaposi's sarcoma, especially in patients with late-stage disease. Basal cell carcinomas were the next most frequent tumor. We have also seen three malignant melanomas and two squamous cell carcinomas. Five patients had malignant lymphoma. One patient had a primary lymphoma of subcutaneous soft tissue; in one patient multiple cutaneous lesions developed. CONCLUSION: The distribution and prevalent types of cutaneous neoplasms in HIV-1-positive patients appear to differ from those found in other immunosuppressed populations. This may be the result of the different patterns and periods of immunosuppression in these patients and/or associated cocarcinogens to which these patients frequently are exposed.

Immunohistochemical features in inflammatory linear verrucous epidermal nevi suggest a distinctive pattern of clonal dysregulation of growth. Military Medical Consortium for the Advancement of Retroviral Research.

BACKGROUND: We studied biopsy material from four patients with inflammatory linear verrucous epidermal nevi (ILVEN) that had a psoriasiform appearance histologically and seven cases of linear epidermal nevi (LEN). Of the seven LEN, five showed hyperkeratosis, papillomatosis, and varying degrees of acanthosis; two had features of epidermolytic hyperkeratosis. Because these lesions have distinctive histologic patterns, we wanted to determine whether we could also demonstrate a distinctive pattern of immunohistochemical markers. METHODS: On all 11 cases we performed immunohistochemical stains for PCNA, factor XIIIa, MAC-387, UCHL-1, and OPD-4. In addition, on one case of ILVEN we performed ICAM-1, ELAM-1, and HLA-DR stains. RESULTS: The pattern of staining of PCNA, factor XIIIa, MAC-387, UCHL-1, and OPD-4 was distinctly different in ILVEN and LEN. Staining for ICAM-1 was present on keratinocytes, and ELAM-1 was present on endothelial cells in two cases of ILVEN. HLA-DR in these same two cases of ILVEN stained mainly dendritic cells in the epidermis. CONCLUSION: The different pattern of staining of PCNA, factor XIIIa, MAC-387, UCHL-1, and OPD-4 in LEN and ILVEN indicates a different mechanism of growth dysregulation. Stains for ICAM-1, ELAM-1, and HLA-DR in ILVEN suggest that an inability to down-regulate the inflammatory infiltrate may be important in the growth dysregulation in ILVEN. In addition, the onset of ILVEN at the time of HIV-1 infection in one patient suggests that HIV-1 infection may be one of many factors that initiates ILVEN in a susceptible person.

Histologic features of foreign body reactions in patients infected with human immunodeficiency virus type 1. The Military Medical Consortium for Applied Retroviral Research.

BACKGROUND: Within a large population of patients seropositive for human immunodeficiency virus type 1 (HIV-1), seven had biopsy specimens that showed foreign body reactions with histologic features different from those seen in non-HIV-1-positive patients. OBJECTIVE: These cases were reviewed to determine whether there was a specific pattern of response to foreign bodies in HIV-1 infection and whether this pattern was related to the stage of disease. METHODS: Biopsy specimens were reviewed to identify ruptured epidermal cysts. These were studied in routine hematoxylin-and-eosin-stained sections and with immunohistochemical stains to characterize the inflammatory infiltrate. RESULTS: The lesions in HIV-1-infected patients contained abundant macrophages with evidence of decreased function and a lack of giant cells. CONCLUSION: These histologic features suggest an early functional deficit before there is a significant decrease in the number of T4 lymphocytes.

Clinical features of inflammatory dermatoses in human immunodeficiency virus type 1 disease and their correlation with Walter Reed stage. Military Medical Consortium for Applied Retroviral Research.

BACKGROUND: As part of a military study of the natural history of human immunodeficiency virus type 1 (HIV-1) disease, all patients entered in the study were examined for cutaneous changes associated with HIV-1 infection. OBJECTIVE: Our purpose was to characterize and record the types of inflammatory dermatoses in a large number of HIV-1-infected patients to determine whether there was a correlation with the stage of disease. METHODS: The clinical findings in each case were compared with the results of cultures and biopsy specimens and correlated with Walter Reed stage. RESULTS: Most of the inflammatory dermatoses were maculopapular eruptions often with prominent follicular involvement, and in some there was a lichenoid component. With increasing Walter Reed stage, many eruptions become papulosquamous, some with psoriasiform scale and some with a hypertrophic lichenoid appearance. CONCLUSION: Although most of the inflammatory eruptions were nonspecific clinically, most cases showed features resembling those in graft-versus-host disease.

Histopathologic and immunohistochemical findings associated with inflammatory dermatoses in human immunodeficiency virus type 1 disease and their correlation with Walter Reed stage. Military Medical Consortium for Applied Retroviral Research.

BACKGROUND: Cutaneous lesions are common in patients with human immunodeficiency virus type 1 (HIV-1) infection. In many cases they are nonspecific inflammatory dermatoses. OBJECTIVE: Our goal was to determine whether features of these inflammatory dermatoses were characteristic of HIV-1 infection and whether the changes correlated with the stage of disease. METHODS: Biopsy specimens of inflammatory dermatoses from 176 HIV-1-infected patients in all Walter Reed stages were reviewed and the changes were compared with each WR stage. RESULTS: The changes found were nonspecific but were suggestive of features described in graft-versus-host disease and became more prominent in late-stage disease. CONCLUSION: A correlation was found between the changes and the stage of disease, and the findings add support to prior reports that at least some of the changes in HIV-1 infection may be autoimmune in origin.

Verrucous lesions secondary to DNA viruses in patients infected with the human immunodeficiency virus in association with increased factor XIIIa-positive dermal dendritic cells. The Military Medical Consortium of Applied Retroviral Research Washington, D.C.

BACKGROUND: Hyperkeratotic lesions caused by varicella-zoster, herpes simplex, or cytomegalovirus occur in patients infected with human immunodeficiency virus type 1 (HIV-1). We have also observed this type of lesion with molluscum contagiosum. OBJECTIVES: These cases were studied to determine whether there are any pathologic changes unique to these lesions. METHODS: The cases were studied by routine microscopic examination and immunohistochemistry. RESULTS: Each case showed changes diagnostic of the viral infection, which was confirmed by immunohistochemical stains for herpes simplex and cytomegalovirus. In the dermis there were fewer inflammatory cells than expected, but there was an increase in factor XIIIa-positive dendritic cells. CONCLUSION: Varicella-zoster, herpes simplex virus, cytomegalovirus, and molluscum contagiosum can cause verrucous lesions in HIV-1-infected patients. These lesions may be related to an increase in factor XIIIa-positive dendritic cells.

Disseminated microsporidiosis (Encephalitozoon hellem) and acquired immunodeficiency syndrome. Autopsy evidence for respiratory acquisition.

Microsporidia are obligate intracellular protozoal parasites that infect a variety of cell types in a broad range of invertebrates and vertebrates. They have recently come to medical attention due to the increased frequency with which members of two microsporidian genera, Enterocytozoon and Encephalitozoon, are being diagnosed in patients with the acquired immunodeficiency syndrome (AIDS). The majority of published reports of human microsporidiosis describe Enterocytozoon infection of small intestinal enterocytes. In addition, a growing number of AIDS patients have been identified with infection due to the two species of Encephalitozoon-Encephalitozoon cuniculi and Encephalitozoon hellem, observed in conjunctival, corneal, and, recently, sinonasal tissues. However, there are scant data regarding the systemic pathology and epidemiology of these infections. This article describes a patient with AIDS who died with systemic Encephalitozoon infection. The etiologic microsporidian was found to be E hellem by using antemortem biochemical and antigenic analyses. A complete autopsy, the first to be reported in a patient with this infection, revealed organisms in the eyes, urinary tract, and respiratory tract. A surprising observation was the occurrence of numerous organisms within the lining epithelium of almost the entire length of the tracheobronchial tree, suggestive of respiratory acquisition. Detailed light and electron microscopic findings and the biological and diagnostic features of microsporidiosis are discussed.

Cutaneous histopathologic, immunohistochemical, and clinical manifestations in patients with hemophagocytic syndrome. Military Medical Consortium for Applied Retroviral Research (MMCARR).

BACKGROUND AND DESIGN: The hemophagocytic syndrome (HPS) is characterized by fever, wasting, generalized lymphadenopathy, hepatosplenomegaly, and pancytopenia, often with associated coagulopathy. The most common cutaneous manifestations are panniculitis and purpura. Cytophagic histiocytic panniculitis fits within the spectrum of HPS, and the most consistent histopathologic feature in HPS is a proliferation of mature histiocytes that exhibit prominent erythrophagocytosis and cytophagocytosis. The clinical spectrum, the underlying causes, and the histopathologic features found in HPS are broad. The characteristic phagocytic histiocytes seen in HPS have been confused with malignant histiocytes in the past, but are now known to be reactive. The clinical findings, histologic, and immunohistochemical features of 10 cases of HPS with cutaneous lesions were reviewed. Immunohistochemical markers included KP-1, beta F-1, UCHL-1, L-26, MAC-387, factor XIIIa, and S100 protein. RESULTS: The HPS was associated with T-cell lymphoma and/or viral infection. Most biopsy specimens showed edema and hemorrhage with a lymphohistiocytic infiltrate and prominent histiocytic cells showing erythrophagocytosis and, in some cases, cytophagocytosis. The histiocytic cells showed positive reactions for KP-1 and negative reactions for the lymphoid markers. In all cases the lymphoid cells showed a mixed pattern with most cells positive for beta F-1 and UCHL-1, and a small percentage positive for L-26. CONCLUSION: In HPS, the prominent phagocytic histiocytes are reactive and are stimulated by T-cell lymphocytes, either neoplastic or in response to viral infection. Many of the findings in the HPS may also be due directly or indirectly to cytokines produced by proliferating T-cell lymphocytes and/or reactive phagocytic histiocytes.