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Apart from autopsy, tissue correlates of coronavirus disease 2019 (COVID-19) clinical stage are lacking. In the current study, cutaneous punch biopsy specimens of 15 individuals with severe/critical COVID-19 and six with mild/moderate COVID-19 were examined. Evidence for arterial and venous microthrombi, deposition of C5b-9 and MASP2 (representative of alternative and lectin complement pathways, respectively), and differential expression of interferon type I-driven antiviral protein MxA (myxovirus resistance A) versus SIN3A, a promoter of interferon type I-based proinflammatory signaling, were assessed. Control subjects included nine patients with sepsis-related acute respiratory distress syndrome (ARDS) and/or acute kidney injury (AKI) pre-COVID-19. Microthrombi were detected in 13 (87%) of 15 patients with severe/critical COVID-19 versus zero of six patients with mild/moderate COVID-19 (P 0.001) and none of the nine patients with pre-COVID-19 ARDS/AKI (P 0.001). Cells lining the microvasculature staining for spike protein of severe acute respiratory syndrome coronavirus 2, the etiologic agent of COVID-19, also expressed tissue factor. C5b-9 deposition occurred in 13 (87%) of 15 patients with severe/critical COVID-19 versus zero of six patients with mild/moderate COVID-19 (P 0.001) and none of the nine patients with pre-COVID-19 ARDS/AKI (P 0.001). MASP2 deposition was also restricted to severe/critical COVID-19 cases. MxA expression occurred in all six mild/moderate versus two (15%) of 13 severe/critical cases (P 0.001) of COVID-19. In contrast, SIN3A was restricted to severe/critical COVID-19 cases co-localizing with severe acute respiratory syndrome coronavirus 2 spike protein. SIN3A was also elevated in plasma of patients with severe/critical COVID-19 versus control subjects (P ≤ 0.02). In conclusion, the study identified premortem tissue correlates of COVID-19 clinical stage using skin. If validated in a longitudinal cohort, this approach could identify individuals at risk for disease progression and enable targeted interventions.

Supplementary Figure from Inhibition of Integrin αVβ3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma

Supplementary Table from Inhibition of Integrin αVβ3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma

Kohlmeier-Degos Disease is a unique thrombotic microvascular and arteriopathic vasculopathy that is highly selective in the organs it targets. It invariably involves the skin and can be a purely cutaneous process. It affects both the microvasculature and the arterial system ranging from a thrombogenic microangiopathy to a fibrointimal obliterative arteriopathy with an accompanying background of extravascular fibrosis. A potentially lethal complication of Kohlmeier-Degos disease is constrictive pericarditis and pleuritis. We present three male patients, ages 26 years, 46 years and 58 years of age with established cutaneous and gastrointestinal Kohlmeier-Degos disease who developed progressive pericarditis which in two necessitated a pericardiectomy. There are 6 other reported cases, 5 in men, with restrictive symptoms developing on average 6 years following the onset of skin disease and all with gastrointestinal involvement. Half of the patients died within one year following the diagnosis of cardiopulmonary restrictive disease. The restrictive symptoms developed within 12 months, 2 years and 11 years following the initial skin presentation. In one patient this complication developed despite receiving eculizumab, indicative that this extravascular fibrosing reaction was not complement mediated as opposed to the thrombotic microvascular component of the disease which is C5b-9 mediated. Two of the three patients had evidence of right ventricular dysfunction. Two of our patients died within 1 year of developing constrictive pericarditis due to progressive cardiopulmonary failure. A profibrogenic process resembling scleroderma was seen given the degree of smooth muscle actin staining along with a mirror image reduction in CD34 expression within the fibrotic pleura and pericardium. There was significant upregulation in type I interferon signaling in cases tested as revealed by the degree of staining for MXA, the surrogate type I interferon marker. We propose that excessive type I interferon signaling results in the influx of monocyte derived dendritic cells with subsequent transdifferentiation into potent collagen producing myofibroblasts. We believe that targeting and suppressing type I interferon signaling should be a cornerstone of early therapy in patients with Kohlmeier- Degos disease to prevent pleural and pericardial fibrosis.

Fil: Cayrol, María Florencia. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Cayrol, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Revuelta, Maria V. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos Fil: Debernardi, Maria Mercedes. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Debernardi, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Paulazo, Maria Alejandra. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Paulazo, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Phillip, Jude M. Johns Hopkins University. Institute for Nanobiotechnology. Chemical and Biomolecular Engineering, Oncology. Departments of Biomedical Engineering; Estados Unidos Fil: Zamponi, Nahuel. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos Fil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Sterle, Helena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Díaz Flaqué, María Celeste. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Díaz Flaqué, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Magro, Cynthia. Weill Cornell Medicine, Department of Pathology and Laboratory Medicine; Estados Unidos Fil: Marullo, Rossella. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos Fil: Mulvey, Erin. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos Fil: Ruan, Jia. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos Fil: Cremaschi, Graciela A. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cremaschi, Graciela A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neuroinmunomodulación y Oncología Molecular; Argentina Fil: Cerchietti, Leandro. Weill Cornell Medicine. Hematology and Oncology Division. Department of Medicine; Estados Unidos Abstract: Bexarotene is a specific retinoid X receptor agonist that has been used for the treatment of cutaneous T-cell lymphoma (CTCL). Because bexarotene causes hypothyroidism, it requires the administration of levothyroxine. However, levothyroxine, in addition to its ubiquitous nuclear receptors, can activate the aVb3 integrin that is overexpressed in CTCL, potentially interfering the antineoplastic effect of bexarotene. We thus investigated the biological effect of levothyroxine in relation to bexarotene treatment. Although in isolated CTCL cells levothyroxine decreased, in an aVb3-dependent manner, the antineoplastic effect of bexarotene, levothyroxine supplementation in preclinical models was necessary to avoid suppression of lymphoma immunity. Accordingly, selective genetic and pharmacologic inhibition of integrin aVb3 improved the antineoplastic effect of bexarotene plus levothyroxine replacement while maintaining lymphoma immunity. Our results provide a mechanistic rationale for clinical testing of integrin aVb3 inhibitors as part of CTCL regimens based on bexarotene administration.

Psoriasis is a common autoimmune dermatosis representing an interplay between certain genetic predisposing factors along with clonally restricted Th1 T cells responding to epidermal keratinocyte derived antigen. A unique IL17/IL23 cytokine-rich milieu is pathogenetically significant and conducive to its salient histomorphologic features, such as epidermal hyperplasia and intraepidermal influx of neutrophils. The classic cutaneous manifestation is that of plaque psoriasis also referred to as psoriasis vulgaris with characteristic well-circumscribed erythematous plaques covered by silvery scales. Follicular psoriasis is an uncommon variant manifesting as a scaly folliculocentric hyperkeratotic eruption of the trunk and extremities, irrespective of the presence or absence of conventional lesions of psoriasis vulgaris. In this study we present 5 cases of follicular psoriasis, review the literature, and provide a proposal regarding relevant pathologic findings and potential pathogenetic mechanisms. The incidence of follicular psoriasis is unknown, emphasizing its rarity given the overall incidence of conventional psoriasis in the general population. Owing to the lack of awareness, this clinical presentation is often mistaken for other follicular dermatoses, including bacterial folliculitis, pityriasis rubra pilaris, keratosis pilaris, or follicular eczema.

Pustular psoriasis occurs rarely in children but can present with acute toxicity requiring inpatient admission. For the best approach, medical providers should have an evidence based and systematic treatment algorithm in their armamentarium. Toillustrate this point, we describe a 13-year-old girl who was admitted with generalized pustular psoriasis and who responded dramatically to "wet wrap" therapy and cyclosporine bridged to etanercept. Using this case example, we highlight the three most important considerations in any patient with new onset pustularpsoriasis: avoidance of disease complications, acute "rescue" therapy, and maintenance therapy.

Lymphomatoid drug reactions can mimic endogenous T and B cell lymphoproliferative diseases.We present a novel form of cutaneous drug reaction with features of pityriasis lichenoides (PL), a recognized form of T cell dyscrasia.Ten cases were studied where a cutaneous eruption exhibiting semblance to PL within a few weeks to months after starting a particular drug.The patient cohort comprised 7 females and 3 males with the mean age of 60 years. Widely distributederythematous cutaneous lesions were present in 6 cases whereas a more localized distribution was seen in three cases. The most frequently implicated drugsassociated with the eruption were antidepressants and statins. Histologic examination showed a morphologic picture identical to PL including marked epitheliotropism of mildly atypical lymphocytes, psoriasiform epidermal hyperplasia, dyskeratosis, hemorrhage, and a thick parakeratotic scale. Therewas a significant reduction in the expression of CD7 and CD62L amid the T cells. Regression of the eruption occurred in all cases excluding one.Thefindings conform the categorization of this process as a form of T-cell dyscrasia albeit one that is reversible, dependent on the drug withdrawal. The limitationof our study includes the retrospective design of the study.

Hydralazine-induced small vessel vasculitis is a rare entity with a limited number of cases reported in the dermatologic literature. A characteristic pattern of acral pseudoembolic vesiculopustules with necrosis and ulceration has been suggested along with involvement of the aerodigestive tract, indicating mucosal involvement is an important feature of this disease. We report the case of a patient with hydralazine-induced vasculitis who exemplified this characteristic presentation associated with severe involvement of the aerodigestive tract and gastrointestinal tract bleeding. In addition to the distinctive clinical presentation, the patient's workup revealed the characteristic antineutrophil cytoplasmic antibody (ANCA)-positive serologic profile. Increased recognition of the clinical and serological features of hydralazine-induced small vessel vasculitis may lead to earlier recognition of this disease and decreased time to discontinuation of hydralazine when appropriate. Drug withdrawal is the cornerstone of therapy, and depending on the severity of symptoms, additional immunosuppressive treatment such as corticosteroids may be necessary.

In 1990, an international grading scheme for the grading of pulmonary allograft rejection was adopted by the International Society for Heart and Lung Transplantation (ISHLT) and was modified in 1995 by an expanded group of pathologists. The original and revised classifications have served the lung transplant community well, facilitating communication between transplant centers with regard to both patient management and research. In 2006, under the direction of the ISHLT, a multi-disciplinary review of the biopsy grading system was undertaken to update the scheme, address inconsistencies of use, and consider the current knowledge of antibody-mediated rejection in the lung. This article summarizes the revised consensus classification of lung allograft rejection. In brief, acute rejection is based on perivascular and interstitial mononuclear infiltrates, Grade A0 (none), Grade A1 (minimal), Grade A2 (mild), Grade A3 (moderate) and Grade A4 (severe), as previously. The revised (R) categories of small airways inflammation, lymphocytic bronchiolitis, are as follows: Grade B0 (none), Grade B1R (low grade, 1996, B1 and B2), Grade B2R (high grade, 1996, B3 and B4) and BX (ungradeable). Chronic rejection, obliterative bronchiolitis (Grade C), is described as present (C1) or absent (C0), without reference to presence of inflammatory activity. Chronic vascular rejection is unchanged as Grade D. Recommendations are made for the evaluation of antibody-mediated rejection, recognizing that this is a controversial entity in the lung, less well developed and understood than in other solid-organ grafts, and with no consensus reached on diagnostic features. Differential diagnoses of acute rejection, airway inflammation and chronic rejection are described and technical considerations revisited. This consensus revision of the working formulation was approved by the ISHLT board of directors in April 2007.

Metastatic Crohn disease is a rare cutaneous manifestation of Crohn disease characterized by granulomatous lesions discontinuous with the diseased areas of the gastrointestinal tract. We report a case of a 32-year-old woman with history of Crohn disease who was admitted for treatment of cellulitis after presenting with a tender erythematous plaque of the left calf. Microbiological tests including tissue cultures were negative. A skin biopsy revealed granulomatous dermatitis consistent with metastatic cutaneous Crohn disease. Owing to concomitant perianal fistulas and abscesses and prior infusion reaction to infliximab, the patient was treated with certolizumab, a pegylated tumor necrosis factor (TNF) inhibitor combined with methotrexate resulting in complete resolution of the skin lesion. This case emphasizes the importance of recognizing this rare skin manifestation of Crohn disease and adds certolizumab as one of TNF inhibitors useful in the treatment of metastatic cutaneous Crohn disease.

Reed syndrome, also known as Multiple Uterine and Cutaneous Leiomyomas (MCUL), is an autosomal dominant defect in the fumurate hydrase gene, leading to a predisposition of leiomyomas of the skin and uterus. Patients with Reed syndrome may present with cutaneous leiomyomas, uterine leiomyomas and/or leiomyosarcomas. A 37-year-old woman presented to the dermatology clinic with several subcutaneous nodules. Punch biopsy was performed and the diagnosis of angioleiomyosarcoma with supervening degenerative changes was made. Medical history was positive for uterine leiomyomas. These concomitant findings led to the diagnosis of Reed syndrome. At the present time, genetic counseling is a suggested screening parameter for patients with multiple cutaneous leiomyomas. The superficial nature of these lesions and the low staging made surgical excision the preferred and actual treatment method. Adjunct radiation and chemotherapy have not been shown to provide clear benefit of survival. Owing to an association with renal cell carcinoma, a referral for nephrology consultation is also recommended.

Sézary syndrome (SS) is a rare, aggressive form of cutaneous T-cell lymphoma. When patients die from SS, it frequently is due to the sequela of the profound endogenous immunosuppression that is typical of this condition. Most cases of SS represent neoplasms of mature postthymic CD4(+) T cells. We present a case of SS that exhibited an unusual double-positive phenotype in which the neoplastic T cells demonstrated CD4 and CD8 expression. The patient's clinical course was unusually aggressive with rapid clinical demise occurring less than 1 year from the initial cutaneous eruption. Our patient had documented involvement of the skin, peripheral blood, and lymph nodes. We also review other anecdotal reports of postthymic T-cell lymphomas manifesting as a double-positive phenotype primarily in the context of adult T-cell leukemia and T-cell lymphoma. The evolution of the postthymic double-positive T-cell phenotype, especially with regard to SS, and the benign lymphocyte counterpart also is discussed.

The first report of spinous follicular lichen nitidus with perifollicular granulomas was by Madhok and Winkelmann in 1988. Since this report, a few cases of follicular or periappendageal lichen nitidus have been described, in a more localized form or without perifollicular granulomas. We describe a 5-year-old girl with the rare generalized spinous follicular variant of lichen nitidus with perifollicular granulomas.

Lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma (ALCL) belong to the spectrum of cutaneous CD30+ lymphoproliferative disorders, an indolent form of T-cell lymphoproliferative disease. We reviewed 21 cases of CD30+ lymphoproliferative lesions expressing cytotoxic profile (CD8+). Seven cases of cutaneous ALCL, 2 cases of systemic ALCL involving the skin, and 12 cases of LyP. The cases of LyP were predominated by small lymphocytes exhibiting a prominent epidermotropic pattern consistent with either type B or type D LyP. Four cases showed co-expression of CD56. The ALCL cases included myxoid features, pseudoepitheliomatous change, and an intravascular component. In all cases that were primary in the skin an indolent clinical course was seen while one patient with systemic myxoid ALCL is in remission following systemic multiagent chemotherapy. The paucity of other neutrophils and eosinophils and concomitant granulomatous inflammation were distinctive features in cases of type B and type D LyP. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful differentiating features from an aggressive cytotoxic CD8+ T cell lymphoma. In all cases that were primary in the skin an indolent clinical course was observed. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful in preventing a misdiagnosis of an aggressive cytotoxic CD8+ T cell lymphoma.

Primary cutaneous B-cell lymphoma (1 degrees CBCL) accounts for 25% of all lymphomas. The difficulty in distinction of reactive from neoplastic B-cell infiltrates prompts the use of molecular diagnostic adjuncts. While T-cell clonality can be seen in various reactive states, clonal B-cell infiltrates are often neoplastic; standard assays employed include polymerase chain reaction (PCR) or Southern blot analysis to assess heavy chain rearrangement. We sought to assess the utility of kappa (kappa) and lambda (lambda) mRNA expression using the Ventana automated assay (Ventana Medical Systems, Tucson, AZ, USA) in the analysis of atypical cutaneous B-cell lymphoid infiltrates.Multiple 4 micro m sections of paraffin-embedded, formalin-fixed skin biopsies from 31 patients with CBCL were placed on silane-coated slides, deparaffinized, then digested in pepsin (5 mg/ml) for 30 min at 37 degrees C. Fluorescein-tagged oligoprobes and tissue mRNA were denatured at 80 degrees C for 5 min, hybridized for 2 h at 37 degrees C, and incubated with antifluorescein alkaline phosphatase conjugates. Detection of the probe target complex employed nitroblue tetrazolium and bromochloroindolyl phosphate conjugates with a nuclear fast red counterstain. A kappa : lambda ratio3 : 1 was held to represent kappa light chain restriction and a kappa : lambda ratio/= 1 : 1 to indicate lambda light chain restriction.The diagnosis in each case was determined by careful integration of clinical, histologic, and phenotypic data. The diagnoses included: pseudolymphoma (PL), marginal zone lymphoma (MZL), 1 degrees CBCL of the trunk, scalp or leg, 2 degrees lymphoma, and plasma cell dyscrasia. All but one case of lymphoma were light chain restricted. All cases of PL were proven to be polyclonal by this methodology. In non-plasmacytic small cell lymphomas, only 5-10% of the infiltrate expressed kappa or lambda, with clonality established through the abnormal kappa : lambda ratio. Interpretations were most difficult in the 2 degrees small cell-dominant follicular center cell lymphomas and easiest in cases with significant plasmacytic differentiation (i.e. MZL, immunocytomas, or plasma cell dyscrasias).The Ventana kappa/lambda assay is a reliable, quick, and inexpensive way to determine B-cell clonality in cutaneous lymphoid infiltrates in paraffin-embedded formalin-fixed tissue.

We describe 9 patients with a novel variant of lymphomatoid papulosis characterized by prominent localization of the infiltrate around the eccrine coil, resulting in nodular expansion of the coil accompanied by variable granulomatous inflammation. Light microscopy, immunohistochemical analysis using antibodies to CD2, CD3, CD4, CD5, CD7, CD8, and CD30 in 6 cases, and polymerase chain reaction--single-stranded conformational polymorphism analysis for T-cell receptor gamma chain gene rearrangement in 5 cases revealed 2 cytomorphologic patterns (large cell dominant with polymorphous inflammation, small cell lymphocyte--rich with an inconspicuous large cell component [phenotypes, CD30+/CD3+/CD4+/CD7-for large atypical cells; reactive for small lymphocytes]) and clonal restriction in 4 and polyclonality in 1 of the lymphocyte-dominant cases. During an average 6-year follow-up, no lymphomas developed. Recognition of this variant is important--accentuation of the infiltrate around the eccrine coil and cutaneous nerves, presence of granulomatous inflammation, dominance of small lymphocytes in the dermis, and variable extension into the panniculus may lead to diagnostic confusion with entities such as discoid lupus erythematosus, Jessner lymphocytic infiltrate of skin, subcutaneous T-cell lymphoma, and persistent arthropod bite reaction. Our findings suggest that pruritus, a younger age at diagnosis, and a more indolent course are defining clinical features.

Since its first description in 1930, the pathogenesis of pyoderma gangrenosum (PG) has remained obscure even as an ever-widening array of systemic diseases has been described in association with it. The histopathologic distinction of PG from other ulcerative processes with dermal neutrophilia is challenging and at times impossible. In consequence, when confronted with a biopsy from such a lesion, the pathologist has an obligation to obtain a full and detailed clinical history. In short, as a diagnosis of PG does not hinge exclusively upon the biopsy findings in isolation from other studies, a solid knowledge of the clinical features, the systemic disease associations and the differential diagnosis will help the pathologist to avoid diagnostic pitfalls or the generation of a report which is non-contributory to patient care. In this review, we describe in detail the different clinicopathologic forms of PG, summarize the diseases associated with this process in the literature and in our experience, and briefly review the treatment options.

Although the histologic characteristics of cryofibrinogenemia have been described in skin lesions, the literature is largely devoid of descriptions of this disorder in other organs. This series is the first to document the histopathologic manifestations of intrapulmonary, intramuscular, and renal cryofibrinogenemia. We describe the histopathologic manifestations of cryofibrinogenemia in 10 cases with manifestations in 4 organ systems: skin in 7 cases, skeletal muscle in 2, lung in 2, and kidney in 1. Irrespective of anatomic site, all lesions showed an occlusive thrombotic diathesis comprising eosinophilic refractile deposits within vessel lumina with extension into the intima, with or without an accompanying characteristic granulomatous vasculitic component. Ultrastructural examination of the renal deposits showed fibrillary material within glomerular capillary lumina with unique morphologic features not previously described. Analysis of plasma from several cases revealed a cold-precipitable protein, which in most cases included a monoclonal paraprotein. The laboratory and histologic distinctions between cryofibrinogenemia and cryoglobulinemia are addressed. We provide guidelines for the proper handling of patient specimens in the workup of cryofibrinogenemia.

The purpose of this study was to correlate the histologic findings of skin lesions clinically suspicious for epidermodysplasia verruciformis with the viral findings in patients with organ transplants or AIDS.Thirty-seven skin biopsies from 17 patients (six with AIDS and 11 with transplants) were studied as a non-randomized, controlled, unblinded case series by in situ hybridization for HPV DNA.Nineteen (51%) of these biopsies were HPV-positive by in situ hybridization either for HPV type 5 (five cases), type 8 (10 cases), type 16 (four cases) or HPV 31 (one case, with one case of dual infection). Only eight of the 19 HPV-positive tissues (42%) showed the classic histologic features of verruca planae. The more common histologic feature significantly associated with HPV detection was a focally thickened and disrupted granular layer (13/19 [68%] vs. 8/18 [44%], p0.04). Dysplasia was evident in 12/19 HPV-positive tissues (63%), which was significantly greater than in patients with congenital epidermodysplasia verruciformis (20%).Oncogenic HPV types are detected in about one-half of skin biopsies from immunocompromised patients with a clinical presentation suspicious for epidermodysplasia verruciformis. Many of these lesions lack the histologic features of verruca planae, a focally thickened granular layer is a marker for viral detection, and the risk for dysplasia in such lesions is much higher than in epidermodysplasia verruciformis not associated with acquired immunosuppression.

We report five cases of aseptic meningitis presenting with high cerebrospinal fluid (CSF) cell counts (260-600 cells/cmm) and mononuclear pleocytosis, suggesting the diagnosis of CNS malignant lymphoma. In four of five cases a reactive background of small lymphocytes, monocytes, and eosinophils was seen. Immunocytochemical studies in all five cases revealed that 100% of the lymphoid cells were T-cells. Three of four cases evaluated for lymphocyte subsets displayed a CD4 to CD8 ratio of 3:1. In the fourth case the CD4:CD8 was 1 to greater than 10; this patient was subsequently proven to have AIDS with HIV meningitis. In this study the cytologic features of the benign atypical lymphoid pleocytosis of aseptic meningitis in contrast to malignant lymphomas in CSF specimens included small or indistinct nucleolus, regular perinucleolar area, smaller widely separated chromatin aggregates, generally ample cytoplasm with perinuclear clearing and polyclonal T-cell immunophenotype.