Lenalidomide in the management of eosinophilic dermatosis of hematological malignancy

Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B‐cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.     

Insect bite-like reaction in patients with hematologic malignant neoplasms

BACKGROUND: Exaggerated reaction to insect bites, mainly to mosquitoes, is infrequently described in patients with chronic lymphocytic leukemia. Skin lesions usually appear months to years after the diagnosis of leukemia and are unrelated to laboratory findings, disease course, or therapy. OBSERVATIONS: We describe 8 patients with various hematologic disorders (chronic lymphocytic leukemia, acute lymphoblastic leukemia, acute monocytic leukemia, mantle-cell lymphoma, large-cell lymphoma, and myelofibrosis) who developed insect bite-like reaction. Although the clinical picture and the histological characteristics of the lesions were typical for insect bites, none of the patients actually had a history, course, or response to treatment suggestive of arthropod assaults. In 2 patients, the eruption preceded the diagnosis of the malignant neoplasm. The rash persisted for months to years and was resistant to therapies other than systemic corticosteroids. The 3 patients with chronic lymphocytic leukemia seemed to have a worse prognosis than expected for their disease. In 1, the polymerase chain reaction detected leukemic cells in the infiltrate. CONCLUSIONS: Insect bite-like reaction is an infrequent, disturbing, and difficult-to-treat nonspecific phenomenon in patients with hematologic malignant neoplasms. Since it may precede the hematologic disorder, oriented evaluation is warranted. We speculate that immunodeficiency plays a role in its pathogenesis; however, the exact pathogenesis and its prognostic implications await further studies.     

Insect bite-like reaction associated with mantle cell lymphoma: a report of two cases and review of the literature

BACKGROUND: An insect bite-like reaction and exaggerated reactions to insect bites are nonspecific phenomena described primarily in association with chronic lymphocytic leukemia (CLL), but also with other hematological malignancies. Two cases of mantle cell lymphoma (MCL), one associated with an insect bite-like reaction and the other with a true hypersensitivity to mosquito bites, have previously been reported in the English language literature. The pathogenesis of the skin eruption may be related to the release of different cytokines that also trigger an IgE elevation and dermal eosinophils. CASE REPORT: We describe two additional cases of MCL associated with an insect bite-like reaction. One patient had been diagnosed with MCL 4.5 years prior to the appearance of the skin eruption, and in the other patient the skin symptoms preceded the diagnosis of the MCL by 2 years and led to its diagnosis. CONCLUSIONS: Insect bite-like reaction may appear in patients with MCL. It is important to recognize this entity because it may be the presenting sign of MCL.     

Sweet's syndrome without granulocytosis

Background Sweet's syndrome (SS), acute febrile neutrophilic dermatosis, has been linked to hematologic malignancies and presents with characteristic edematous dermal plaques. Peripheral blood neutrophilia is frequently seen in association with SS and is one of the diagnostic criteria.
Objective To report the clinical, laboratory, and hematologic data of four patients with myeloid leukemia who developed SS after chemotherapy. Three of these patients were neutropenic.
Methods A retrospective study of four patients with SS and hematologic malignancies was undertaken. Three patients had de novo acute myelogenous leukemia and one was in the acute blast crisis of chronic myelogenous leukemia.
Results Sweet's syndrome was not originally suspected in these patients because of the low peripheral white blood cell counts caused by chemotherapy. All of the patients presented with fevers, arthralgias, and an eruption. They had been treated with antibiotics because of a presumed infection. Once the correct diagnosis was made and oral prednisolone was started, a rapid response followed.
Conclusions Sweet's syndrome should be considered in the differential diagnosis when acute myeloid leukemic patients develop skin lesions and unexplained fevers regardless of the peripheral blood counts.     

Small lymphocytic lymphoma mimicking primary cutaneous marginal zone lymphoma with colonization of germinal center follicles

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is primarily a disease of older adults and is occasionally an incidental finding on skin biopsies accompanying epithelial neoplasms and insect bite reactions. In rare instances, however, it produces leukemic infiltrates showing clinical and histopathologic overlap with primary cutaneous B‐cell lymphomas including primary cutaneous marginal zone lymphoma (PCMZL). Even less frequently, such findings serve as the initial disease manifestation. We present an exceptional case of a 61‐year‐old man with no past medical history whose clinical and histopathologic findings raised consideration for PCMZL with abnormal B‐cells colonizing germinal center follicles; however, faint CD5 and CD23 co‐expression raised the differential diagnosis of CLL/SLL. In light of an ambiguous clinical presentation with widely distributed papules and plaques, peripheral blood flow cytometry was also performed, revealing high count of CLL‐type monoclonal B lymphocytosis. Subsequent workup revealed bone marrow involvement and mesenteric lymphadenopathy, supporting the diagnosis of SLL. Follicular colonization by SLL has not been previously reported. Our case underscores the importance of subtle immunophenotypic clues and correlations with clinical and radiologic findings in the workup of B‐cell lymphomas presenting in the skin.     

Eosinophilic cellulitis (Wells' syndrome) associated with colon carcinoma

Eosinophilic cellulitis (Wells' syndrome) is an inflammatory dermatosis characterized by marked eosinophilic infiltrates. Drugs and various infections are recognized causes of eosinophilic cellulitis. Eosinophilic cellulitis has been reported in non‐hematological malignancies in two patients with squamous cell carcinoma and one with nasopharyngeal carcinoma. We report the association of eosinophilic cellulitis with adenocarcinoma of the colon. Curative hemicolectomy led to a complete remission, suggesting that underlying malignancies can trigger eosinophilic cellulitis.     

Typically atypical: histiocytoid Sweet syndrome, associated with malignancy

Sweet syndrome (acute febrile neutrophilic dermatosis) is characterized by a dramatic onset of high fever, neutrophilia and typical skin lesions. About 20 % of patients have an associated malignancy, most commonly hematologic diseases. Chronic and paucisymptomatic manifestations of Sweet syndrome may be misdiagnosed or misinterpreted as harmless, resulting in delayed diagnosis. "Atypical" manifestations are especially suspicious for associated malignancies. This is demonstrated by a 39-year old patient with chronic and afebrile disease who was referred to our clinic only after symptoms had persisted for several months. By that point, an underlying nodular lymphocyte predominant Hodgkin's lymphoma had already reached an advanced stage. Skin biopsies revealed dermal infiltrates of histiocytoid cells of myelogenous origin, supporting a diagnosis of histiocytoid Sweet syndrome. Specific cutaneous infiltrates associated with myelogenous leukemia were ruled out.     

Lymphoma- and leukemia-associated cutaneous atypical CD30+ T-cell reactions

Cutaneous CD30+ lymphoid infiltrates appear cytologically atypical and occasionally may be misinterpreted as recurrent disease when they occur in patients treated for other primary hematologic malignancies. We recently encountered two such cases and present our findings. One patient with B-cell lymphoma and another with myeloid leukemia developed cutaneous eruptions after chemotherapy displaying highly atypical perivascular lymphoid cells on histology that mimicked recurrent disease. In both cases, the lymphocytes were CD30+ T cells by immunohistochemistry. The skin lesions spontaneously resolved and have not recurred. Because one case was initially misinterpreted as recurrent leukemia, we conclude that close clinical correlation and immunophenotypic confirmation should be done for atypical cutaneous lymphoid infiltrates in patients with primary hematologic malignancies. We discuss the differential diagnosis of atypical CD30+ infiltrates in this setting, which include recurrent lymphoma or myeloid leukemia, primary cutaneous anaplastic large cell lymphoma (ALCL), lymphomatoid papulosis (LyP), carbamazepine-induced CD30+ pseudolymphoma, viral infection and an atypical eruption of lymphocyte recovery.     

Bullous eosinophilic cellulitis succession with eosinophilic pustular folliculitis without eosinophilia

Eosinophilic cellulitis is characterized clinically by an acute dermatitis resembling cellulitis with unknown etiology. Eosinophilic pustular folliculitis is also a rare inflammatory dermatosis characterized by recurrent crops of erythematous follicular papulopustules that coalesce to form annular plaques with unclear etiopathogenesis. We describe a 20-year-old white male who had vesiculobullous and plaque-like lesions on the hands and feet and was diagnosed with bullous eosinophilic cellulitis clinically and histologically without any etiological agents. Following therapy with oral corticosteroid and oral tetracycline capsules, the lesions disappeared. After a 2-month asymptomatic period, the patient developed pruritic follicular papules and pustules on the lower and upper extremities and upper back. Stool examination revealed Gierdia intestinalis eggs. The patient had complete clearance with treatment of ornidazol for 2 weeks and indomethacin for 2 months. This is the first report of bullous eosinophilic cellulitis coexisting with eosinophilic pustular folliculitis without eosinophilia in the English published work.     

Actinic granuloma occurring in an unusual association with cutaneous B-cell chronic lymphocytic leukemia

Granulomatous cutaneous reactions are well described in association with T-cell non-Hodgkin lymphoma and Hodgkin lymphoma, but are rarely seen in association with B-cell non-Hodgkin lymphoma or leukemia. We report a case of a 65-year-old woman with B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who presented with multiple, tender, firm pink papules on the face, upper trunk and upper extremities 6 years after diagnosis of CLL. Biopsy revealed both palisading granulomatous dermatitis consistent with actinic granuloma and a dense perivascular lymphocytic infiltrate consistent with the patient's known history of leukemia. This is an unusual manifestation of cutaneous B-cell CLL that is rarely seen.     

Insect bite-like reaction associated with mantle cell lymphoma: clinicopathological, immunopathological, and molecular studies

A cutaneous eruption simulating insect bites has been repeatedly described in association with chronic lymphocytic leukemia (CLL). It was only rarely described with mantle cell lymphoma (MCL). Our study was performed to elucidate the clinical, histologic, immunopathological, and molecular characteristics of insect bite like reaction (IBLR) associated with MCL. The clinical presentation and histologic findings in 3 IBLR cases associated with MCL were found to be similar to 3 IBLR cases associated with CLL. The eruptions consisted of itchy erythematous papules, nodules, plaques, and vesicles. Non-vesicular lesions were characterized histologically by normal or mildly spongiotic epidermis. Vesicular lesions were characterized by marked spongiosis and intraepidermal spongiotic vesicles containing eosinophils, or marked subepidermal edema occasionally leading to a dermoepidermal separation. Most of the lesions were characterized by superficial and mid dermal to deep perivascular and interstitial, and occasionally periadnexal, inflammatory-cell infiltrate consisting of mononuclear cells and eosinophils. The densities of the infiltrates varied and the inflammatory-cell infiltrate extended often into the fat lobules. Neutrophils and nuclear dust were found more frequently and abundantly in the IBLR lesions associated with MCL. Immunophenotyping, direct immunofluorescence (DIF) tests, and IgH gene rearrangement studies were performed in the lesions associated with MCL only. The majority of the infiltrating lymphocytes were CD3+, CD5+ and CD43+, more CD4+ than CD8+, and only a small minority was CD20+. The cells did not stain for bcl-1 protein and CD30, and with no evidence of clonality. The DIF test result was negative. The IBLR eruption associated with MCL resembles clinically and histologically IBLR associated with CLL. The eruption seems to be reactive rather than neoplastic, because there is no evidence of MCL involvement in the skin lesions.     

Concurrent eosinophilic fasciitis and cutaneous T-cell lymphoma. Eosinophilic fasciitis as a paraneoplastic syndrome of T-cell malignant neoplasms?

Eosinophilic fasciitis has been reported to precede hematologic malignant neoplasms such as myelomonocytic leukemia, lymphocytic leukemia, and Hodgkin's lymphoma. In this case study, eosinophilic fasciitis occurred concurrently with cutaneous T-cell lymphoma (mycosis fungoides). The clinical diagnosis of eosinophilic fasciitis was based on painful sclerodermatous lesions on the extremities and trunk without acrosclerosis. There was histologic confirmation with edema and lymphocytic inflammation in the superficial muscular fascia and dermis. Deposition of immune reactants was found in the fascia and dermis. In addition, peripheral eosinophilia and circulating immune complexes were detected. The diagnosis of cutaneous T-cell lymphoma (mycosis fungoides) was based on extensive erythematous cutaneous plaques, dermal and epidermal lymphocytic atypia, loss of pan-T-cell immunologic markers, and a cutaneous lesional T-cell receptor beta-chain rearrangement by Southern blot analysis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome associated with hematologic malignant neoplasms, including mycosis fungoides. Cytokines or lymphokines released by activated immunocytes, either malignant leukocytes or normal leukocytes reacting to malignant cells, may be responsible for the eosinophilia and sclerosis seen in these associated hematologic malignant neoplasms.     

Neutrophilic eccrine hidradenitis secondary to thioguanine in a neutropenic patient

Neutrophilic eccrine hidradenitis (NEH) is an infrequent, self-limited inflammatory dermatosis characterized by a neutrophilic infiltrate around the eccrine glands. Clinically, it presents with different types of lesions. NEH occurs most frequently in patients who have undergone chemotherapy for hematologic neoplasms. We present a case of NEH in a 70-year-old neutropenic male who received thioguanine for acute myeloid leukemia. The erythematous plaques disappeared in 3-4 weeks. The histological findings were compatible with NEH. Skin cultures ruled out infectious causes.     

Dermatosis eosinofílicas (I)

The eosinophil is an effector cell of the immune response with important affinity for the tissues. Skin diseases characterized by a dermal infiltration of eosinophils constitute an apparently heterogeneous group. We review the characteristic features of such well-defined entities, known as eosinophilic dermatoses.In the first part of this work we included eosinophilic pustular folliculitis, eosinophilic cellulitis, angiolymphoid hyperplasia with eosinophilia, granuloma faciale, eosinophilic ulcer of the tongue, papuloerythroderma and the pachydermatous eosinophilic dermatitis.In analogy to the accepted unifying concept of neutrophilic dermatosis, we will discuss the possible pathogenic unity of this group of diseases.     

Therapierefraktäre Hautinfiltrate bei chronisch lymphatischer Leukämie

Chronic lymphocytic leukemia (CLL) is a low-grade B-cell non-Hodgkin lymphoma. Skin involvement is observed in up to 25% of patients. A 70-year-old men with presented with prominent erythematous facial infiltrates. After the diagnosis of CLL was established, he showed a good hematologic response to the monoclonal antibody rituximab, but the skin infiltrates were therapy-resistant.     

Ofuji's disease with unusual histological features

A 20-year-old lady presented with a 3-month history of an itchy eruption affecting her face and trunk. Erythematous annular plaques with follicular papules and pustules at the margins were present on her face consistent with Ofuji's disease. A perifollicular and perivascular eosinophil-rich infiltrate was seen histologically, with infiltration of the follicular epithelium by eosinophils and formation of eosinophilic microabscesses. An unusual feature was the presence of follicular mucinosis. Treatment with dapsone resulted in an improvement in the eruption after 2 weeks. Ofuji's eosinophilic pustular folliculitis is becoming increasingly frequently recognized, and may not be as rare as initial reports suggested.     

Atypical pyoderma gangrenosum as a manifestation of childhood acute lymphoblastic leukemia

Pyoderma gangrenosum is a neutrophilic dermatosis that may occur idiopathically or in association with various systemic diseases and malignancy. Although the association of this entity with myeloid malignancies is well known, its association with lymphoid malignancy is extremely rare. We describe atypical pyoderma gangrenosum in association with acute lymphoblastic leukemia in a 2-year-old child, an occurrence not reported before.     

Eosinophilic panniculitis: a clinicopathologic study

Study of 18 patients with biopsy diagnoses of eosinophilic panniculitis revealed diverse patterns of systemic disease, including Wells' syndrome, vasculitis, atopy, and erythema nodosum as well as localized panniculitis. Significant associated diseases included psychiatric illness, 6 (drug dependency, 4); atopy, 5 (asthma, 3); malignancies, 5; immune complex vasculitis, 4; thyroid disease, 2; Wells' eosinophilic cellulitis, 2; glomerulonephritis and sarcoidosis, 1 each. The skin lesions varied from urticarial papules and plaques to purpura, pustules, and ulcerative lesions but always included a nodular subcutaneous component, frequently as a presenting complaint. Eosinophilic panniculitis is a non-specific finding that can signify localized disease, such as an insect bite or injection lipophagic granuloma in a drug-dependent patient, or systemic lymphoma or immune reactive disease. Eosinophilic panniculitis in erythema nodosum is perhaps its most confusing presentation.     

Primary cutaneous follicle center lymphoma in the setting of chronic lymphocytic leukemia

Primary cutaneous malignancies arising in association with chronic lymphocytic leukemia (CLL) are notable for their atypical clinical and histological presentation. We report a 69-year-old man with a 17-year history of CLL who presented for evaluation of a well-defined red to violaceous nodule with a central depressed scar on the left lower extremity. Microscopic examination of a punch biopsy revealed an infiltrate of predominantly small lymphocytes with scattered large, atypical epithelioid cells. Immunohistochemical stains revealed diffuse positive staining of the lesional cells with CD20+ and bcl-6+ and focal positive staining with bcl-2+ (negative CD10 and CD23), findings which, in conjunction with the histology, were most compatible with a diagnosis of primary cutaneous follicle center lymphoma (PCFCL). A review of the clinical charts revealed several prior biopsies with varied diagnoses. In light of the most recent biopsy findings, all previous biopsies were re-reviewed and interpreted as PCFCL arising in the setting of CLL. Features contributing to the diagnostic conundrum in this case included an atypical clinical and histological presentation, lack of pertinent clinical history and multiple presentations at different institutions.