Hairy cell leukemia variant: a morphologic, immunologic and clinical study of 7 cases

Hairy cell leukemia (HCL), a well-recognized chronic lymphoproliferative disorder, is frequently characterized by pancytopenia, monocytopenia, splenomegaly and marrow fibrosis, which typically leads to an unsuccessful bone marrow aspiration (dry tap). Patients with a high white cell count without neutropenia and/or monocytopenia, with an aspirable and hypercellular marrow, splenomegaly and neoplastic cells with hairy cell features have been recently recognized and classified as HCL variants. We report here the clinical, hematological and immunological features of 7 such cases. All patients presented splenomegaly with a high leukocyte count; 2 were anemic and only 1 thrombocytopenic. Five patients were treated with alpha-Interferon (alpha-IFN) but 4 failed to achieve any significant response; two of these were subsequently splenectomized and successfully treated with Chlorambucil. Splenectomy, followed by Chlorambucil, was performed at diagnosis in the remaining 2 cases, both of which achieved a partial response and are alive and well. Six out of the 7 patients are still alive. The recognition of these peculiar patients is also important because they most often do not respond to alpha-IFN, while splenectomy, followed by Chlorambucil, may be a reasonable therapeutic option for them.     

Waldenström's macroglobulinemia: clinical course and prognostic factors in 60 patients

Waldenstr?m's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by the presence in patients' serum of an IgM monoclonal component. We report on our experience with 60 WM patients, focusing on their clinical findings, response to treatment, and the possible identification of prognostic factors. Of these patients, 70% presented with fatigue, and lymphadenopathy was observed in 22%, splenomegaly in 18%, hepatomegaly in 13%, and extranodal site of involvement in 6%. Bleeding tendency was seen in 17%, infections in 17%, hyperviscosity syndrome in 12%, and cardiac failure in 25% of the patients. The median of IgM levels was 30 g/l with hypoalbuminemia in 20% of cases, hypogammaglobulinemia in 27%, polyclonal hypergammaglobulinemia in 15%, kappa light-chain restriction in 78%, and Bence-Jones proteinuria in 54%. Anemia was frequent (85%), followed by leukocytosis (18%), lymphocytosis (12%), leukopenia (10%), and thrombocytopenia (10%). Cryoglobulinemia and autoimmune hemolytic anemia were encountered in 5%. In all cases but two, bone marrow was involved. Of 50 patients initially treated with intermittent oral chlorambucil, 46 (92%) responded. Median overall survival was 108 months. Factors associated with adverse prognosis were age > or =65 years (p=0.06), presence of lymphadenopathy (p=0.06), bone marrow infiltration > or =50% (p=0.007), international prognostic index (IPI) > or =3 (p=0.0001), and Morel's scoring system (p=0.04). Concluding, we found in this series of WM patients that chlorambucil is an effective treatment and that the parameters of age, lymphadenopathy, percentage of bone marrow infiltration, IPI, and Morel's scoring system carry prognostic significance.     

The control of chronic lymphocytic leukemia with mediastinal irradiation

Forty patients with chronic lymphocytic leukemia have been treated with mediastinal irradiation. A full remission was achieved in 18 (45 per cent) patients, a partial response in eight (20 per cent), "WBC control" in eight (20 per cent) and no response in 6 (15 per cent). Although mediastinal irradiation benefited all stages of disease, earlier stages of disease correlated with more complete and longer response to mediastinal irradiation. Toxicity was mild and transient and included leukopenia in five patients (12 per cent), thrombocytopenia in eight patients (20 per cent), mild esophagitis in 12 patients (30 per cent) and pneumonitis in four patients (10 per cent). There were no toxic deaths and mediastinal irradiation did not adversely effect survival. Treatment was readily given on an ambulatory basis and completed within four weeks. In five of 11 patients, abnormal immunoglobulins became normal. Eleven patients had abnormal lymphocyte transformation with PHA, five had marked improvement and three had partial improvements following mediastinal irradiation. This improvement appeared to correlate with response and survival but further study is necessary to confirm this relationship. Although most patients required additional therapy within two years, eight patients have required no further therapy for periods of twenty-eight months to thirteen years.     

Correlation of immunophenotype with clinical features in T-cell acute lymphoblastic leukemia

The immunophenotype of leukemicblasts from 111 patients with T-ALL or T-NHL were further examined by using a panel of standardized McAbs of CD nomenclature to human leukocyte differentiation antigens. Four major subsets of T-ALL were defined: pre T-ALL, immature T-ALL (I), common T-ALL (II) and mature T-ALL (III), with the percentages 20.7%, 20.7%, 20.7% and 37.0% respectively. In addition there was a case with M-T acute hybrid leukemia. Some of the clinical features of the patients with T-ALL and T-NHL were compared. It was found that male predominance, older age, higher leukocyte count, lower platelet level, relative higher hemoglobin level and increased incidence of extramedullary involvement, including hepatomegaly, splenomegaly and lymphadenopathy were alike for all subsets of T-ALL cases. However, the average white cell level and incidence of lymphadenopathy in the pre T-ALL subset significantly differed from those in other subsets. The correlation of immunophenotype with morphologic characterization was also discussed in this paper.     

Hairy-cell leukemia: a rare blood disorder in Asia

We report a 68-year-old Indian man who was referred to the Hematology Unit for investigation for thrombocytopenia, an incidental finding during a pre-operative screening for prostatectomy. Physical examination was unremarkable. There was no splenomegaly, hepatomegaly or lymphadenopathy. Complete blood counts showed normal hemoglobin and total white cell count with moderate thrombocytopenia. Hairy-cell leukemia was diagnosed based on peripheral blood film, bone-marrow aspirate and trephine biopsy findings, supported by immunophenotyping results by flow cytometry. The purpose of this report is to create awareness of this uncommon presentation and to emphasize that a single-lineage cytopenia or absence of splenomegaly does not exclude the diagnosis of hairy-cell leukemia. Careful attention to morphological detail is important for early diagnosis, especially when low percentages of "hairy" cells are present in the peripheral blood and bone marrow. Early diagnosis is important to ensure that patients obtain maximum benefit from the newer therapeutic agents that have greatly improved the prognosis in this rare disorder.     

Angioimmunoblastic T cell lymphoma (AITL) with autoimmune thrombocytopenia

We present a case of angioimmunoblastic T cell lymphoma (AITL) with autoimmune thrombocytopenia. A 85-year-old man was admitted to our hospital with thrombocytopenia, generalized lymphadenopathy, pleural effusion, and splenomegaly in June 2000. Blood chemistry revealed hemoglobin and platelet counts of 8.8 g/dL and 26 x 10(9)/L, respectively. The level of platelet-associate-IgG was 2568.9 ng/10(7) cells. The direct Coombs test was positive. The level of serum IL-6 was 10.2 pg/ml. Megakaryocytes in the bone marrow increased. Lymph node biopsy showed diffuse proliferation of atypical lymphoid cells with a clear cytoplasm accompanied by plasma cells and small vessels. He was diagnosed as having AITL with autoimmune thrombocytopenia and hemolytic anemia. He received repeated platelet transfusion, and a limited effect of prednisolone therapy on his platelet count was observed. Combination chemotherapy lessened the extent of the lymphadenopathy and slightly elongated the interval of platelet transfusion. We next performed splenic irradiation and a slight increase in the platelet count was observed. He died of pneumonia in August 2000. Autoimmune thrombocytopenia associated with AITL is rare and the therapy containing prednisolone and chemotherapy is reported to be partly effective. Our case showed a minor response of autoimmune thrombocytopenia to splenic irradiation. Therapeutic intervention for hypersplenism should be considered if thrombocytopenia is not improved by chemotherapy alone.     

Chlorambucil in the treatment of uveitis and meningoencephalitis of Behçet's disease

Among 21 patients with Behçet's disease, the results of various treatments were assessed. Treatment with chlorambucil, 0.1 mg/kg daily, compared favorably with corticosteroids. Uveitis and visual acuities improved in five of seven eyes when the patients were treated with chlorambucil, whereas improvement was observed in only four of 13 eyes when treatment consisted of corticosteroids. In 19 treatment courses among 14 patients with meningoencephalitis or recurrent meningitis, eight of nine patients treated with chlorambucil had remission of their disease; eight of 10 treatment courses with other agents—generally, corticosteroids—failed to induce remission in any of eight patients. Elevated cerebrospinal fluid cell counts returned to normal in five of nine patients treated with chlorambucil but remained elevated in five of six patients treated with corticosteroids. Two patients died, one who was taking prednisone plus cyclophosphamide and the other after prednisone plus multiple immunosuppressive treatments. Toxicity from chlorambucil included leukopenia (two patients), thrombocytopenia (one), bronchopneumonia (one), and amenorrhea (two). The duration of chlorambucil therapy averaged 1.8 years both for patients with uveitis and for those with meningoencephalitis.     

Chronic lymphocytic leukemia in India--a clinico-hematological profile

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in elderly people. The clinico-hematological profile and treatment outcome of patients with CLL were assessed using retrospective case record analysis over 11 years. There were 95 (75 males: 20 females) patients with a median age of 61 years. Thirty patients were aged 55 years or less (young CLL patients) and 65 were more than 55 years of age (elder CLL patients). Sixty percent patients had non-specific complaints, such as weakness, cough and indigestion. Twenty-six (27%) patients had pallor and 24 (25%) had fever as initial presenting manifestation. Bleeding manifestations were seen in 7 patients. Seven patients were diagnosed incidentally. Lymphadenopathy, splenomegaly and hepatomegaly were seen in 52 (55%), 63 (66%) and 60 (63%) patients, respectively. The median white blood cell count and absolute lymphocyte counts were 70,600 and 51,490/mul, respectively. Three patients had autoimmune hemolytic anemia. Twenty-five patients (26%) had anemia with hemoglobin < 11 g/dl and thrombocytopenia with platelet count 100 x 10(3)/mm(3) was seen in 17 (18%). Interstitial nodular, mixed and diffuse bone marrow (BM) involvement was seen in 10.2, 67.3, 6.1 and 16.3% cases, respectively. Eighteen (60%) young patients and 35 (54%) older patients required treatment with chlorambucil. The mean time from initial diagnosis to treatment was 4.6 +/- 10.7 months. None of our patient attained complete response. Six patients obtained partial response. Median duration of chlorambucil was 7 months (1-86 months). Forty-six patients had stable disease. Three patients died. Median survival of study group was 4 years (8 months-13 years). In older CLL it was 4 years (8 months-11 years) and in young patients, survival duration was 5.5 years (1-13 years).     

Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia

We describe the clinical and laboratory findings of 78 adult patients with T-prolymphocytic leukemia (T-PLL) studied over the last 12 years. The main disease features were splenomegaly (73%), lymphadenopathy (53%), hepatomegaly (40%), skin lesions (27%), and a high leukocyte count (greater than 100 x 10(9)/L in 75%) with nucleolated prolymphocytes. A variant form with small, less typical cells was recognized in 19%. Membrane markers defined a postthymic phenotype TdT- , CD2+, CD3+, CD5+, CD7+; in 65%, the cells were CD4+ CD8-, in 21%, they coexpressed CD4 and CD8, and, in 13%, they were CD4- CD8+. Serology for human T-cell leukemia/lymphoma virus Type-I (HTLV-I) was negative in the 27 cases investigated. Cytogenetic analysis in 30 cases showed a consistent abnormality of chromosome 14, usually inv (14), with breakpoints at q11 and q32 in 76% of cases. Trisomy 8, including iso8q, was shown in 53%; t (11;14)(q13;q32) was documented in one case; and one had a normal karyotype. The clinical course was progressive with a median survival of 7.5 months. Thirty-one patients were treated with 2' deoxycoformycin and 15 responded (3 complete remissions and 12 partial remissions); the response rate (48%) increased to 58% in patients with a CD4+ CD8- phenotype. The median survival of responders was 16 months and of nonresponders 10 months; other treatments were less effective. T-PLL is a distinct clinico-pathologic entity with aggressive course and characteristic chromosome abnormalities. A subgroup of patients may benefit from deoxycoformycin.     

Characteristics of type I Gaucher disease associated with persistent thrombocytopenia after treatment with imiglucerase for 4-5 years

The characteristics of Gaucher disease (GD) associated with persistent thrombocytopenia despite imiglucerase enzyme therapy in type 1 GD (GD1) were investigated by retrospective analysis of International Collaborative Gaucher Group (ICGG) Registry data. The study involved 1016 GD1 patients with an intact spleen for whom date of diagnosis, therapy initiation, and platelet counts were known, and who received continuous imiglucerase therapy for 4 to 5 years. These patients were stratified by last platelet count: ≥ 120 × 10(9) /l (n = 772); ≥ 100 to <120 × 10(9) /l (n = 94); ≥ 80 to <100 × 10(9) /l (n = 80); and <80 × 10(9) /l (n = 70; 20 with <60 × 10(9) /l) and characterized by initial and cumulative average imiglucerase dose, body mass index, platelet count, anaemia, hepatomegaly, splenomegaly, and skeletal assessments at baseline and after 4-5 years of therapy. Statistically significant associations were found between persistent thrombocytopenia and baseline platelet count (<80 × 10(9) /l), splenomegaly, and anaemia (all P < 0·0001). After 4-5 years, statistically significant associations were found with splenomegaly (P < 0·0001), anaemia (P < 0·0001), white blood cell count (P = 0·049), hepatomegaly (P = 0·004) and bone pain (P = 0·035). Exponential platelet decay in relation to splenomegaly suggests that platelets increase only when spleen volume decreases substantially.     

Reactive Hemophagocytic Syndrome in Adult-Onset Still Disease: Clinical Features,Predictive Factors,and Prognosis in 21 Patients

Hemophagocytic syndrome (HPS) is a potentially life-threatening complication of systemic inflammatory disorders. Adult-onset Still disease (AOSD) is one of the systemic autoimmune diseases associated with reactive hemophagocytic syndrome (RHS). This study aimed to evaluate the characteristic findings, predictive factors, and prognosis of RHS in patients with AOSD.We retrospectively evaluated 109 patients diagnosed with AOSD and reviewed their clinical data and laboratory findings, including the biopsy results of 21 AOSD patients with RHS. Moreover, data from 17 hemophagocytic lymphohistiocytosis (HLH) patients evaluated during the same period were compared with those from the RHS patients.Twenty-one patients (19.3%) developed RHS during the course of AOSD, and only 7 patients (6.4%) were confirmed by bone marrow, liver, or lymph node biopsy. AOSD patients with RHS showed significantly higher frequencies of splenomegaly, hepatomegaly, and lymphadenopathy than did those without RHS. Moreover, patients with RHS showed significantly higher relapse rates than those without RHS (61.9% vs 18.2%, P < 0.001). Possible triggering factors inducing hemophagocytosis were detected in 16 of 21 RHS patients (76.2%): disease flare in 12 patients (75%), infection in 3 patients (18.8%), and drug use in 1 patient (6.3%). AOSD patients with RHS showed higher frequencies of leukopenia, anemia, thrombocytopenia, hypoalbuminemia, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, and elevated lactate dehydrogenase levels than did those without RHS. Multivariate logistic regression with forward selection procedure showed that low platelet count (<121,000/mm³), anemia, and hepatomegaly were independent predictors of RHS. Patients with definite RHS and those with probable RHS showed comparable results. Although RHS is a life-threatening complication of AOSD, long-term prognosis was observed to be similar in patients with and those without RHS. Compared to RHS patients, HLH patients had poor prognosis, such as higher death rates (52.9% vs 9.5%, P = 0.005).RHS can be considered when an AOSD patient shows at least 2 of the following 3 findings: low platelet count, anemia, and hepatomegaly. Diagnostic confirmation by biopsy may not be essential if typical clinical findings of RHS are present. Moreover, prognosis of RHS was better than that of HLH diagnosed by the presence of trilineage cytopenia at admission.     

Adult Still's disease

The clinical and laboratory features in six patients with adult Still's disease are presented and compared with those in 52 other cases gathered from the literature. Although there is no pathognomonic abnormality, the condition can be readily recognized by the striking constellation of clinical and laboratory abnormalities. The typical rash occurs in 90 per cent of the cases, arthritis in 88 per cent, a fever with temperatures of 40 °C or more in 83 per cent and leukocytosis of 18,000 cells/mm³ or more in 67 per cent. One or more of the following are frequently found: lymphadenopathy (48 per cent), splenomegaly (45 per cent), pleuritis or pneumonitis (31 per cent) and pericarditis (26 per cent). The initial therapy of choice is high doses of nonsteroidal anti-inflammatory drugs. This is not an uncommon disease, as was once thought, and awareness of it will avoid unnecessary diagnostic procedures and delay in initiating therapy.     

Autoimmune Lymphoproliferative Syndrome (ALPS) in a Boy with Massive Lymphadenopathy

Autoimmune lymphoproliferative syndrome (ALPS) is an uncommon nonmalignant lymphoproliferative disease which is characterized by chronic, persistent or recurrent lymphadenopathy, splenomegaly, hepatomegaly, immune cytopenia , hypergammaglobinemia and increased risk of lymphoma. We report a 2-year old boy with hepatosplenomegaly as first presentation. Petechial and purpuric rashes with massive cervical lymphadenopathies developed 10 months later.In laboratory tests anemia, thrombocytopenia and hypergammaglobinemia were observed. According to flocytometry increased double negative T cells and by apoptosis assay decrease apoptosis of lymphocytes accompanied clinical manifestations, thus diagnosis of ALPS was established. In conclusion; in all patients with massive lymphadenopathy and hepatosplenomegay; especially with cytopenia; ALPS should be considered.     

Chronic lymphocytic leukemia in India-A clinico-hematological profile

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in elderly people. The clinico-hematological profile and treatment outcome of patients with CLL were assessed using retrospective case record analysis over 11 years. There were 95 (75 males: 20 females) patients with a median age of 61 years. Thirty patients were aged 55 years or less (young CLL patients) and 65 were more than 55 years of age (elder CLL patients). Sixty percent patients had non-specific complaints, such as weakness, cough and indigestion. Twenty-six (27%) patients had pallor and 24 (25%) had fever as initial presenting manifestation. Bleeding manifestations were seen in 7 patients. Seven patients were diagnosed incidentally. Lymphadenopathy, splenomegaly and hepatomegaly were seen in 52 (55%), 63 (66%) and 60 (63%) patients, respectively. The median white blood cell count and absolute lymphocyte counts were 70,600 and 51,490/μl, respectively. Three patients had autoimmune hemolytic anemia. Twenty-five patients (26%) had anemia with hemoglobin <11 g/dl and thrombocytopenia with platelet count 100 × 10³/mm³ was seen in 17 (18%). Interstitial nodular, mixed and diffuse bone marrow (BM) involvement was seen in 10.2, 67.3, 6.1 and 16.3% cases, respectively. Eighteen (60%) young patients and 35 (54%) older patients required treatment with chlorambucil. The mean time from initial diagnosis to treatment was 4.6 ± 10.7 months. None of our patient attained complete response. Six patients obtained partial response. Median duration of chlorambucil was 7 months (1–86 months). Forty-six patients had stable disease. Three patients died. Median survival of study group was 4 years (8 months–13 years). In older CLL it was 4 years (8 months–11 years) and in young patients, survival duration was 5.5 years (1–13 years).     

Therapy of essential thrombocythemia with thiotepa and chlorambucil

Twenty-seven patients with essential thrombocythemia were treated with combination chemotherapy consisting of weekly intravenous thiotepa (until the platelet count fell below 1,000 X 10(3)/cu mm) and daily chlorambucil (until a sustained remission, platelet count less than 400 X 10(3)/cu mm). All patients responded promptly, platelet counts fell to below 1,000 X 10(3)/cu mm by 1-3 wk, and were less than 400 X 10(3)/cu mm by 2-6 wk. Remission of thrombocytosis was accompanied by an improvement of the patients' symptoms and resolution of the splenomegaly that was present in 21 of the 27 patients. However, daily chlorambucil for more than 1 yr was required to produce a sustained remission in the majority of patients. Nine of 21 patients whose initial treatment was discontinued have required retreatment. To date, 3 patients have expired; 1 patient developed acute leukemia at 36 mo.     

Bacterial infection as a presenting manifestation of visceral leishmaniasis

Two patients admitted to the hospital because of severe bacterial infection were diagnosed as having visceral leishmaniasis. The types of bacterial infection were perianal abscess and pneumonia; Escherichia coli and Streptococcus pneumoniae were isolated from exudates and blood cultures, respectively. A third patient admitted because of acute necrotizing infection of the pharynx and visceral leishmaniasis is also discussed. Cultures from this patient failed to yield pathogens. Anemia, leukopenia, or thrombocytopenia was present in all patients, and bone marrow aspirate revealed the presence of Leishmania in macrophages. We conclude that in areas where leishmaniasis is endemic, early bone marrow aspirate should, in most instances, be performed in patients with bacterial infection associated with anemia, leukopenia, or thrombocytopenia if hepatomegaly and/or splenomegaly is present.     

Mycobacterium genavense infection in a patient with long-standing chronic lymphocytic leukaemia

We describe the first case of disseminated infection with Mycobacterium genavense in an HIV-seronegative patient with a chronic haematological disorder. Our patient, an 80-year-old woman, had been under long-term treatment with chlorambucil (partially in combination with prednisone) for B-cell chronic lymphocytic leukaemia (B-CLL). When she developed general fatigue and progressive anaemia, as well as progressive lymphadenopathy and splenomegaly, bone marrow biopsy revealed granulomas with acid-fast bacilli, and cultures of both bone marrow and blood grew M. genavense. The patient's CD4+ cell count was approximately 100 microL(-1). Treatment with clarithromycin, ethambutol and rifabutin resulted in improvement of anaemia and general health as well as in regression of lymphadenopathy and splenomegaly.     

Waterborne typhoid fever in Dade County, Florida. Clinical and therapeutic evaluation of 105 bacteremic patients.

An extensive outbreak of waterborne typhoid fever occurred in 1973 at a migrant labor camp in Dade County, Florida. Blood cultures from 105 of the 188 patients with proved or presumptive cases of typhoid fever grew Salmonella typhi. The clinical and laboratory findings in these patients were reviewed. Fever, usually with temperatures above 38.8 degrees C and of the sustained type, was a primary manifestation of disease, although a majority of the patients also complained of headache and gastroenteric symptoms. Hepatic or splenic enlargement was present in 52 per cent and 42 per cent, respectively, whereas rose spots were detected in only 13 per cent. The total leukocyte count was normal in 74 per cent, but serum levels of liver and muscle enzymes were frequently elevated. Gastrointestinal, pulmonary and neurologic complications were infrequent; circulatory failure was not observed. Defervescence in response to antibiotic therapy was variable; however, the median response among 68 patients who received chloramphenicol was two days less than that in 34 patients treated with ampicillin. There was one possible treatment failure with ampicillin. The relapse rate of 10 per cent in chloramphenicol-treated patients was not significantly greater than the 3 per cent rate among those treated with ampicillin. Serologic studies for typhoid fever were of limited diagnostic value since the titer of agglutinins was 1:160 or higher in 49 per cent of the serums obtained before treatment, and a fourfold rise in titer occurred in only 24 per cent of 57 patients studied. The serologic response to chloramphenicol treatment did not differ from that to ampicillin.     

THE ONCOGENICITY OF CHLORAMBUCIL IN RHEUMATOID ARTHRITIS

Chlorambucil is useful in patients with rheumatoid arthritis(RA) refractory to other agents but there is concern about therisk of haematological malignancy with this agent. A retrospectivesurvey was performed to assess the incidence of all types ofmalignancy in 39 patients treated with chlorambucil (mean dailydose 4.25 mg, mean duration of treatment 25 months). These patientswere compared with 30 patients with RA who received contemporaneously,the purine analogues azathioprine or 6-mercap-topurine (meandose 100 mg, mean duration of treatment 24 months). Eight patientstreated with chlorambucil and one patient receiving purine analoguesdeveloped cutaneous malignancy (p = 0.03). In the chlorambucil-treatedpatients these were mostly multiple and recurrent. Three patientstreated with chlorambucil developed myeloid leukaemia or a preleukaemicstate, whilst no patient treated with purine analogues developedthis complication. The use of chlorambucil in RA is associatedwith an increased risk of cutaneous as well as haematologicaloncogenesis. KEY WORDS: Rheumatoid arthritis, Chlorambucil, Leukaemia, Cutaneous malignancy     

Erythroderma with atypical lymphocytes. (Sézary syndrome)

A clinical, histopathologic and cytologic study of erythroderma with atypical lymphocytes (Sézary syndrome) was carried out in 19 patients observed at the Mayo Clinic. Cutaneous lesions may begin as dermatitis or infiltration. Erythroderma, pruritis and edema, alopecia, keratoderma and onychodystrophy were cutaneous features of the syndrome. Benign lymphadenopathy and hepatomegaly were observed; spleen and bone marrow findings were normal. The atypical lymphocyte is present in the skin and in the blood. Four patients died of aggressive chemotherapy. Lymphoma developed in three patients. In five recent patients remission has been achieved with the use of cortico-steroids and chlorambucil.