Myxoid variant of primary cutaneous anaplastic large cell lymphoma: First 2 cases

Anaplastic large cell lymphoma (ALCL) is a CD30+ T‐cell non‐Hodgkin lymphoma with 2 main clinical presentations: primary cutaneous ALCL (pcALCL) and systemic ALCL (sALCL). While rare cases of myxoid sALCL have been reported, there are no previous cases of myxoid pcALCL reported. We present 2 unusual cases of pcALCL showing prominent collections of dermal mucin closely intermingling with the anaplastic lymphocytes. Patient 1 was a 30‐year‐old woman who presented with ulcerated nodules on her neck, abdomen, chest and shoulders. A systemic lymphoma was excluded by physical examination, positron emission tomography and computed tomography (PET‐CT) scan, as well as by bone marrow biopsy and flow cytometry studies. The patient was closely followed‐up for 10 months without evidence of systemic involvement. The biopsy showed diffuse infiltration of the dermis by a CD2+, CD30+, anaplastic lymphoma kinase (ALK)‐negative ALCL. Patient 2 was a 55‐year‐old woman who presented with a single nodule on her right arm. A systemic lymphoma was excluded by physical examination as well as by a PET‐CT scan. The biopsy showed diffuse and dense lymphoid infiltration of the whole biopsy by a CD3+, CD4+, CD30+, ALK‐negative ALCL. The atypical lymphocytes were intermingled with large amounts of dermal stromal mucin.     

Relapsing lymphomatoid papulosis after allogenic bone‐marrow transplant

Lymphomatoid papulosis (LyP) is a rare cutaneous lymphoproliferative disorder in children, which can rarely be associated with a cutaneous or systemic lymphoma. We report a 13‐year‐old girl who presented with typical LyP and pathological features of subtype A. Six months later, the patient presented with rapidly progressive peripheral and systemic lymphadenopathy. On examination of a lymph‐node biopsy, a lymphoid infiltrate negative for anaplastic lymphoma kinase (ALK) and positive for CD30 was found, suggestive of systemic anaplastic large T‐cell lymphoma (S‐ALCL). The patient was treated with chemotherapy, followed by allogeneic bone‐marrow transplant (BMT). Over the following 6 years, she presented with biopsy‐confirmed LyP relapses with complete cutaneous, peripheral‐blood and bone‐marrow chimerism. This is only the third reported paediatric association of S‐ALCL with LyP to our knowledge, and seems to be the first paediatric case of recurrent relapses of LyP after bone‐marrow allograft for S‐ALCL with total (100%) cutaneous and bone‐marrow chimerism. LyP occurring after allogenic BMT does not appear to be donor‐derived.     

Bone evaluation in ten adults with cutaneous mastocytosis

BACKGROUND: To systematically evaluate the bone status, searching for osteoporosis in patients with cutaneous mastocytosis. PATIENTS AND METHODS: In a prospective study from March 1997 to June 2000, we included all new patients examined for cutaneous signs of mastocytosis. Past history, physical examination, skin biopsy, laboratory tests, bone densitometry, cytology and histopathology of bone marrow and other complementary investigations were performed in all these patients. RESULTS: Ten patients were included. Two patients had osteoporosis. Five others had osteopenia. Four patients had bone marrow involvement due to mastocytosis. One of these four patients had myelodysplasia. DISCUSSION: This study suggests better investigation of bone density and bone marrow in patients who have cutaneous mastocytosis. Systematic histopathology of bone marrow and osteodensitometry help to detect patients with systemic involvement. Bone densitometry is particularly effective for early detection of patients at risk for fracture and is of practical interest since patients with osteoporosis can now be treated with Pamidronate.     

ALK‐positive (2p23 rearranged) anaplastic large cell lymphoma with localization to the skin in a pediatric patient

Anaplastic large cell lymphoma (ALCL) either as primary cutaneous or nodal disease is rare in children and difficult to distinguish, which is important both prognostically and for treatment purposes. We present a case of anaplastic lymphoma kinase (ALK)+ skin‐limited ALCL that highlights this challenge and draws attention to pitfalls in assessing ALK status. The patient was an 11‐year old girl with a twice recurrent nodule on her right shoulder. Each biopsy revealed a deep infiltrate of atypical lymphocytes that expressed CD3, CD4, CD43, CD45RO and CD30. The initial biopsy was epithelial membrane antigen (EMA)+ with vague cytoplasmic ALK‐1 positivity by immunohistochemistry, while the second biopsy was EMA+ and nuclear ALK‐1+. Fluorescence in situ hybridization analysis for an ALK (2p23) rearrangement of the first specimen was negative, while an ALK gene rearrangement was present in the second specimen. Therefore, this case was treated as nodal ALCL, despite negative bone marrow and radiographic imaging studies. The patient was treated with combination chemotherapy and remains disease‐free. Demonstration of nuclear ALK‐positivity, ALK (2p23) gene rearrangement is suggestive of systemic ALCL. Without evidence of systemic disease, this case highlights challenges of skin‐limited ALCL, whose clinical behavior as either cutaneous ALCL systemic ALCL may not be immediately apparent.     

Bone marrow involvement in cutaneous mastocytosis

BACKGROUND: Cutaneous mastocytosis is considered a relatively benign and indolent form of mast cell disease, which either ultimately regresses, remains stable or is only slowly progressive. Previously, it has been purported that no more than 60% of adult patients with cutaneous mastocytosis will have occult bone marrow involvement. OBJECTIVES: To investigate the frequency of bone marrow involvement in patients with mastocytosis but without systemic symptoms. METHODS: Bone marrow aspirate and trephine biopsy were performed in 13 consecutive patients with cutaneous mastocytosis attending our department. RESULTS: All but one of these patients had evidence of bone marrow involvement. Bone marrow cytogenetic abnormalities have been found in patients with cutaneous mastocytosis: all our patients who were analysed showed a normal karyotype. CONCLUSIONS: Bone marrow involvement is common in adults with cutaneous mastocytosis.     

Pediatric case of anaplastic lymphoma kinase‐positive anaplastic large cell lymphoma forming a solitary skin tumor on the forearm

A 5‐year‐old girl noticed a rapidly growing reddish nodule on her right forearm. Although oral antibiotics had been administrated for 2 weeks, the tumor enlarged. Skin biopsy revealed excessive infiltration of atypical neoplastic cells expressing CD4, CD30 and anaplastic lymphoma kinase (ALK). These histological and immunohistochemical findings were consistent with anaplastic large cell lymphoma (ALCL). Computed tomography showed multiple lymphadenopathy, but lymph node biopsy and bone marrow examination did not show any evidence of systemic dissemination. However, due to the positive results for ALK and multiple lymphadenopathy, we diagnosed ALK‐positive ALCL forming a solitary skin tumor on the forearm. The patient received chemotherapy and presented marked improvement. This paper discusses the difficulty of diagnosing pediatric ALK‐positive ALCL limited to the skin and reviews the medical published work.     

HIV‐associated primary cutaneous anaplastic large cell lymphoma: a clinicopathological subset with more aggressive behavior? Case report and review of the literature

Human immunodeficiency virus (HIV)‐infected patients carry an increased risk of lymphomagenesis. Although the majority of HIV‐related lymphomas have a B‐cell phenotype, the incidence of peripheral T‐cell lymphomas (PTCL), including primary cutaneous subtypes, may be up to 15‐fold higher than in the general population, with anaplastic large cell lymphomas (ALCL) accounting for 18–28% of HIV‐associated PTCL. In contrast to systemic ALCL, the relation between HIV infection and primary cutaneous ALCL has been relatively neglected in the literature. We report the case of a primary cutaneous ALCL occurring in a 76‐year‐old patient with advanced HIV infection, and showing unusually aggressive course. Neither ALK1 immunohistochemical positivity nor evidence of EBV infection were detected; staging procedures at initial presentation ruled out systemic involvement. We provide a summary of the literature regarding primary cutaneous ALCL in HIV‐infected patients. We draw attention to clinicopathological features, prognostic implications and therapeutic quandaries of HIV‐related primary cutaneous ALCL. Further, we propose that a significant fraction of HIV‐associated cases might represent a more aggressive subset of primary cutaneous ALCL.     

Diffuse large B cell lymphoma progression with skin involvement: A case report

Diffuse large B cell lymphoma (DLBCL) constitutes the most frequent subtype of all non-Hodgkin's lymphomas. DLBCL is an aggressive disease and extranodal involvement is seen in approximately 30% of patients and most common extranodal sites are gastointestinal tract and skin. Skin involvement may be either primary or secondary. Secondary cutaneous lymphoma has a worse prognosis. The case is here reported of a 56-year old male DLBCL patient with cutaneous lesions and aggressive clinical course. The patient had no skin lesions at diagnosis and during follow up and treatment period, skin, cerebrospinal fluid and bone marrow involvement was occurred. Salvage chemotherapy and autologous stem cell transplantation was planned but the patient died before the second cycle of salvage chemotherapy. In contrast to primary cutaneous lymphoma, which tends to be more indolent, secondary skin involvement is associated with unfavourable prognosis. In conclusion it should be kept in mind that skin can be involved in lymphoma patients and in these cases, skin biopsy should be performed rapidly.     

ALK‐positive primary cutaneous anaplastic large cell lymphoma: a case report and review of the literature

Anaplastic large cell lymphoma (ALCL) limited to the skin is a distinct disease that is designated primary cutaneous ALCL (pcALCL). It has an indolent course with a significantly better prognosis compared to systemic ALCL (sALCL). Anaplastic lymphoma kinase (ALK) expression in lesions of cutaneous ALCL is classically considered to be a marker for skin involvement by sALCL. However, recent reports of patients with ALK‐positive pcALCL challenge this concept and raise prognostic and therapeutic dilemmas. Herein, we report a case of ALK‐positive pcALCL in a 45‐year‐old woman who was treated with local radiotherapy. We review previously reported cases in the literature to better characterize this rare variant. Overall, the rates of cutaneous recurrence, systemic dissemination, and disease‐related mortality in ALK‐positive pcALCL do not differ from those previously reported in pcALCL. ALK‐positive pcALCL is diagnosed at younger age and has a better disease course in children compared to adults with lower incidences of skin recurrence and progression to systemic disease. We conclude that ALK‐positivity in cutaneous ALCL does not necessarily imply systemic disease. ALK‐positive pcALCL has an excellent prognosis and should be treated by excision and/or radiotherapy. However, patients must remain under close long‐term follow‐up as recurrence and progression to systemic disease may occur.     

¿Está siempre indicada la biopsia de médula ósea en los pacientes con linfoma primario cutáneo de células B de la zona marginal?

Bone marrow involvement at the time of diagnosis is uncommon in patients with primary cutaneous marginal zone B-cell lymphoma (PCMZL). Moreover, in these patients such involvement is rarely found in isolation on diagnosis. Typically the few patients with PCMZL who have early bone marrow involvement also present secondary nodal or visceral involvement, which is detected by other staging studies (usually computed tomography). In recent years, this has given rise to some debate about whether a bone marrow biopsy should be routinely performed in patients diagnosed with PCMZL in view of the good prognosis and low incidence of bone marrow infiltration and/or extracutaneous involvement in this type of lymphoma.     

Subclinical chronic lymphocytic leukemia with atypical cutaneous presentation

Chronic lymphocytic leukemia (CLL) involving skin is a rare but well‐documented occurrence, mainly reported in advanced disease. In contrast, CLL presenting with skin lesions is exceedingly rare, only few reports existing to date. We report a 70‐year‐old man who presented with two non‐pruritic, papular lesions on the lower abdomen and proximal thigh. Biopsies showed dense lymphohistiocytic infiltrates involving the reticular dermis and subcutis without epidermotropism consisting mostly of small, CD20 and PAX‐5‐positive B‐cells expressing CD5, CD23, CD43 and BCL2. Numerous large B‐cells were present in a T‐cell, histiocyte‐rich background. A staging bone marrow biopsy showed a clonal B‐cell proliferation with typical CLL flow cytometry immunophenotyping but neither lymphadenopathy nor absolute lymphocytosis was present. Numerous B and T‐cell cutaneous lymphoproliferative disorders can be associated with increased numbers of histiocytes occasionally masquerading as benign disorders. This was the case with our patient's lesions, originally interpreted as cutaneous Rosai–Dorfman disease. A high index of suspicion from both the pathologist and the dermatologist is essential in identifying these rare but probably underrecognized occurrences of early systemic lymphoproliferative disorders presenting as cutaneous lesions with an unexpected cellular composition. Ali L, Cheney R, Merzianu M. Subclinical chronic lymphocytic leukemia with atypical cutaneous presentation.     

Epstein-Barr virus in CD30 anaplastic large cell lymphoma involving the skin and lymphomatoid papulosis in South Korea

BACKGROUND: Epstein-Barr virus (EBV)-associated cutaneous lymphoproliferative disorders are prevalent in Asia, and less frequent in Western countries. AIM: To elucidate the possible association of EBV with CD30+ anaplastic large cell lymphoma (ALCL) involving the skin and lymphomatoid papulosis (LyP) in South Korea. METHODS: In situ hybridization for EBV-encoded small RNA (EBER) and immunohistochemistry including viral latent membrane protein-1 (LMP-1) were performed on formalin-fixed, paraffin-embedded skin specimens of 26 cases of LyP and 16 cases of CD30+ ALCL involving the skin which were selected from six university hospital medical centers in South Korea. RESULTS: In situ hybridization studies showed positivity of the neoplastic cells for EBER in two of 16 cases of CD30+ ALCL and in none of the cases of LyP. One EBER-positive case was cutaneous CD30+ ALCL with concurrent lymph node involvement. The other was CD30+ ALCL involving the skin and other organs, including lymph nodes, bone, lung, and spleen. Immunostaining for LMP-1 was also positive only for the two cases of EBER-positive CD30+ ALCL. CONCLUSION: LyP and primary cutaneous CD30+ ALCL are very rarely associated with EBV in South Korea.     

Aleukemic leukemia cutis presenting as benign-appearing exanthema.

Aleukemic leukemia cutis is a rare condition characterized by the infiltration of the skin by leukemic cells before their appearance in the peripheral blood or bone marrow. We report here a 62-year-old seemingly healthy patient who presented with disseminated erythematous maculae. A skin biopsy showed leukemia cutis of monocytic type. No involvement of bone marrow or peripheral blood was found. The patient developed acute monocytic leukemia 7 months later. We present this case to illustrate how leukemia cutis can masquerade as a clinically benign-appearing cutaneous eruption without leukemic changes in blood or bone marrow. To confirm the diagnosis of aleukemic leukemia cutis, immunohistochemistry of the skin lesions as well as a complete staging procedure is necessary.     

Langerhans cell histiocytosis first presenting in the skin in adults: frequent association with a second haematological malignancy

Background Langerhans cell histiocytosis (LCH) in adults first presenting in the skin is rare. Guidelines for staging, treatment and follow‐up are lacking. Objectives To better define staging procedures, treatment results and clinical course in adult patients with LCH first presenting in the skin. Methods Eighteen adult patients with LCH first presenting in the skin were collected from five centres collaborating in the Dutch Cutaneous Lymphoma Group. Clinical records and (skin) biopsy specimens were reviewed and follow‐up data were obtained. A literature search on adult patients with LCH presenting in the skin was performed. Results Staging procedures showed extracutaneous disease in three of 16 patients who were adequately staged. One patient had a histologically confirmed lytic LCH bone lesion, while two patients had a myelodysplastic syndrome. During follow‐up two of 18 patients developed extracutaneous localizations of LCH. Five patients developed a second haematological malignancy, including (myelo)monocytic leukaemia (two cases), histiocytic sarcoma (one case), diffuse large B‐cell lymphoma (one case) and peripheral T‐cell lymphoma (one case). Review of the literature revealed six other adult patients with a second haematological malignancy preceding or following a diagnosis of LCH. Conclusions The results of the present study suggest an increased risk of a second haematological malignancy in adult patients with LCH presenting in the skin. Extensive staging at presentation and long‐term follow‐up are therefore warranted in such patients.     

Cutaneous Anaplastic Large-Cell Lymphoma Should be Evaluated for Systemic Involvement Regardless of ALK-1 Status

Anaplastic large-cell lymphoma (ALCL) is a lymphoma that expresses CD30. Cutaneous ALCL presents either as primary cutaneous disease or as secondary skin involvement due to the systemic disease. Herein, we describe two patients who presented to dermatology for evaluation of skin lesions diagnosed by non-dermatologists as a cutaneous abscess and lupus erythematosus, respectively. Upon investigation by a team of medical dermatologists and dermatopathologists, systemic ALCL with secondary skin involvement was discovered in both patients. The majority of cases of systemic ALCL with cutaneous involvement express anaplastic lymphoma kinase-1 (ALK-1), and are associated with a more favorable prognosis than ALK-1-negative cases. However, cutaneous ALCL regardless of ALK-1 status may be secondary to systemic lymphoma. This article stresses the importance of dermatologists being aware of the diagnosis of systemic lymphoma based on cutaneous findings, and being aggressive in initiating appropriate diagnostic testing. Primary cutaneous ALCL and systemic ALCL are reviewed.     

Primary cutaneous mantle cell lymphoma with blastic features: report of a rare case with special reference to staging and effectiveness of chemotherapy

We describe a case of blastic primary cutaneous mantle cell lymphoma (MCL) in an 83-year-old male with a complex medical history. The patient presented to his primary care physician with a nodular erythematous skin eruption on his thighs. Histopathologic examination showed a diffuse lymphoid infiltrate of intermediate to large cells that involved the dermis and subcutis but spared the epidermis. Immunohistochemical staining showed expression of CD20, CD5 and cyclin-D1. The lymphoma cells were negative for CD10 and CD23. Fluorescence in situ hybridization (FISH) analysis revealed a characteristic translocation [t(11;14)(q13;q32)], which is diagnostic of MCL. Cutaneous involvement by MCL is typically secondary because of widespread disease, and primary cutaneous MCL can only be diagnosed in the absence of extracutaneous involvement. Primary cutaneous MCL is extremely rare and requires proper clinical staging. In this case, clinical staging revealed no evidence of bone marrow or peripheral blood involvement, and positron emission tomography (PET) scan revealed weak, abnormal uptake only in a few cervical lymph nodes. Because of the lack of disseminated involvement, we favor the lesion to be a primary cutaneous MCL.     

Systemic B-cell lymphoma presenting as an isolated lesion on the ear

We report a case of systemic B-cell lymphoma that presented as an isolated cutaneous lesion on the ear, mimicking a primary cutaneous B-cell lymphoma. Although there was no clinical evidence of systemic disease, bone marrow involvement was found on further investigation and subsequent immunoglobulin gene analysis revealed an identical clone in the skin lesion and bone marrow aspirate. Evidence of a t(14 : 18) translocation was not identified. This case is unusual for several reasons. First, involvement of the pinna as a presenting feature of systemic lymphoma has not been reported previously. Second, the cutaneous lesion had been present for 3 years prior to diagnosis and there has been no clinical progression of systemic lymphoma during 2 years of follow-up. Third, the lymphoma does not correspond exactly to any of the entities in the REAL classification of systemic B-cell lymphoma. This case underlines the indolent nature of some systemic B-cell lymphomas and the need to investigate thoroughly patients with disease apparently confined to the skin.     

Adult mastocytosis: a review of the Santo António Hospital 's experience and an evaluation of World Health Organization criteria for the diagnosis of systemic disease

BACKGROUND

Mastocytosis is a clonal disorder characterized by the accumulation of abnormal mast cells in the skin and/or in extracutaneous organs.

OBJECTIVES

To present all cases of mastocytosis seen in the Porto Hospital Center and evaluate the performance of World Health Organization diagnostic criteria for systemic disease.

METHODS

The cases of twenty-four adult patients with mastocytosis were reviewed. Their clinical and laboratorial characteristics were assessed, and the properties of the criteria used to diagnose systemic mastocytosis were evaluated.

RESULTS

The age of disease onset ranged from 2 to 75 years. Twenty-three patients had cutaneous involvement and 75% were referred by dermatologists. Urticaria pigmentosa was the most common manifestation of the disease. One patient with severe systemic mast cell mediator-related symptoms showed the activating V560G KIT mutation. The bone marrow was examined in 79% of patients, and mast cell immunophenotyping was performed in 67% of the participants. Systemic disease was detected in 84% of cases, and 81% of the sample had elevated serum tryptase levels. All the diagnostic criteria for systemic mastocytosis had high specificity and positive predictive value. Bone marrow biopsy had the lowest sensitivity, negative predictive value and efficiency, while the highest such values were observed for mast cell immunophenotyping. Patients were treated with regimens including antihistamines, sodium cromoglycate, alpha-interferon, hydroxyurea and phototherapy.

CONCLUSIONS

Cutaneous involvement is often seen in adult mastocytosis patients, with most individuals presenting with indolent systemic disease. Although serum tryptase levels are a good indicator of mast cell burden, bone marrow biopsy should also be performed in patients with normal serum tryptase, with flow cytometry being the most adequate method to diagnose systemic disease.     

Clinical spectrum of primary cutaneous CD30‐positive anaplastic large cell lymphoma: an analysis of the Mannheim Cutaneous Lymphoma Registry

Background: Primary cutaneous CD30⁺ anaplastic large cell lymphomas (C‐ALCL) have indolent clinical behavior with an estimated 5‐year survival rate of 95%. The clinical features and disease courses of C‐ALCL identified in the lymphoma registry of Mannheim University hospital are described in the following. Patients and methods: All C‐ALCL patients identified in the database were analyzed in regard to clinical picture, histology, immunohistochemistry, molecular biology, staging, therapy, follow‐up, and outcome. Results: 14 C‐ALCL patients were identified. The mean age was 69 years and 57% were men. Solitary skin lesions in one anatomical region were seen in 12 patients upon initial diagnosis. Two patients presented with multiple lesions at different anatomical sites. In 2 patients there was specific lymph node involvement. In one C‐ALCL patient, follow‐up over 17 months revealed extracutaneous infiltration. Half of the patients relapsed and 36% had multiple episodes. The majority of our patients were treated with surgical excision followed by electron beam radiotherapy. The 5‐year survival rate was 93% in C‐ALCL. Conclusions: The clinical presentation of C‐ALCL varies. Staging procedures and a close clinical pathological correlation at initial diagnosis are essential. Due to a high rate of relapses and the possibility of developing extranodal manifestations over the course of the disease, close follow‐up is recommended.     

Leucemia cutánea en un paciente con leucemia mieloide aguda M2

—The leukemia cutis is the cutaneous infiltration by leukemics cells. Patients with acute myelogenous leukemia (AML) present specific cutaneous involvement in approximately 10% of the cases.We report the case of a leukemia cutis in a 73-year-old male with AML-M2. The patient presented with a one-week history of general malaise, asthenia, cough, dysnea and fever. Physical examination revealed and indurated red-brown plaque on his back of two moths duration, which was pruritic. Concomitance blood and bone marrow findings were diagnostic of AML-M2. A cutaneous biopsy was consistent with leukemia cutis. A CT and a bronchial biopsy showed pulmonary involvement. Since starting chemotherapy the patient had complete remission and the cutaneous lesion cleared, but 15 days later the skin lesion reappeared. A new bone marrow examination revealed recurrent leukemia. He died one month later.