Cutaneous presentation of aleukemic monoblastic leukemia cutis - a case report and review of literature with focus on immunohistochemistry

Aleukemic monoblastic leukemia cutis is a rare cutaneous manifestation of a systemic hematological disorder associated with dermal infiltration of monoblasts preceding bone marrow or peripheral blood involvement. We report a case of a 75-year-old woman who presented with an erythematous maculopapular rash, which was clinically diagnosed as viral exanthema. Microscopy of the skin biopsy showed features of monoblastic leukemia. Her general physical condition rapidly deteriorated and she died 4 weeks later. We present this case to alert dermatologists of innocuous erythematous skin lesions clinically resembling a viral exanthema, which, in rare instances, may be a presenting feature of an aleukemic monoblastic leukemia cutis. This entity poses problems for dermatopathologists even on immunohistochemistry as monoblasts are negative for hemopoietic precursor cell antigens like CD34, Terminal deoxynncleotidy1 transferase (TdT) and CD117.     

Development of mycosis fungoides after bone marrow transplantation for chronic myeloid leukaemia: transmission from an allogeneic donor

We report on a patient who developed donor‐derived cutaneous T‐cell lymphoma (CTCL) 4 years after successful treatment of chronic myeloid leukaemia with an allogeneic bone marrow transplant. The patient developed an eczematous rash unresponsive to topical therapy and immunosuppression. When CTCL was diagnosed in the recipient, his sibling donor had been attending his local dermatology unit with a maculosquamous rash, which proved subsequently to be mycosis fungoides. An identical pattern of donor and recipient clonality assessment and T‐cell receptor gene sequencing indicated that the CTCL was probably transmitted in the bone marrow harvest. This suggests that CTCL cells circulate in the marrow at an early subclinical stage in this disease. This is the second case of donor‐derived CTCL reported to date.     

Acute monocytic leukemia presenting as cutaneous involvement

Specific cutaneous lesions appearing during acute monocytic leukemia (AMoL) are more frequent than those associated with other types of leukemia. However, skin involvement preceding the presence of leukemic cells in the peripheral blood is quite rare. In this paper, we describe a case where a 25-year-old male had multiple infiltrative erythemas and nodules on his arms. Histologically, the nodules were formed by masses of tumor cells in the dermis. Peripheral-blood tests revealed no abnormalities, but bone marrow aspiration from the sternum led to a diagnosis of AMoL. The diagnosis of specific cutaneous lesions of AMoL was confirmed by the results of cytochemical studies of bone marrow smears, and cutaneous nodules of cutaneous biopsy specimens led to early diagnosis. Complete remission was achieved with combination chemotherapy and peripheral blood stem cell transplantation. Copyright (R) 2000 S. Karger AG, Basel     

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.     

Pathogenetic mechanisms of vitiligo in a patient with Sézary syndrome

Patients exhibiting association between vitiligo and cutaneous T-cell lymphoma (CTCL) remain rare and it is not known whether some T-cell subpopulations of CTCL in the skin are able to recognize specific melanocytic epitopes and thus induce vitiligo. The aim of our study was to determine whether T cells specific to melanocyte differentiation antigens were detectable among tumour-infiltrating lymphocytes (TIL) in the hypopigmented skin of a patient with Sézary syndrome (SS). A 71-year-old patient presented with SS and developed vitiligo during the course of her disease. Immunohistochemical studies showed staining with HMB45 and MelanA antibodies in the pigmented skin biopsy, whereas no staining was observed in the hypopigmented skin biopsy. To analyse responses to melanocyte differentiation antigens, we used a transient COS transfection assay that permits an estimation of CD8 T-cell responses against a large number of HLA/antigen combinations. This technique allowed the detection of melanocyte differentiation antigen-specific T lymphocytes, directed mainly against Melan-A/MART1 antigen in the HLA-A*23 context. Our study supports the concept that vitiligo that has developed during the evolution of a CTCL is related to the presence of a T-lymphocyte subpopulation reactive against melanocyte differentiation antigens (mainly Melan-A/MART1) present in skin lesions. The role of interferon in the induction of this T-lymphocyte subpopulation is discussed.     

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.     

Cutaneous involvement as a presenting feature of monocytic leukemia: morphological and immunohistochemical studies

The clinical and pathological findings in a patient with monocytic aleukemic leukemia presenting initially as multiple monoblastic tumors of the skin is described. The patient was a 35-year-old Japanese woman, who had first noticed multiple, asymptomatic, reddish-brown papules on her trunk. Asymptomatic enlargements of several lymph nodes were present in the bilateral cervical and axillary areas. There was no hepatosplenomegaly, sternal tenderness, bruising, or bleeding. The skin and lymph node biopsies were originally interpreted as malignant lymphoma. The diagnosis of acute monocytic leukemia was established when bone marrow involvement was detected. Immunohistochemical observation of the skin eruptions revealed the following: Positive staining with lysozyme was noted in almost half of the infiltrating atypical cells. Most of the infiltrating cells reacted positively with antisera to Leu-M5 and some of them reacted to Leu-M1. The helper T cell antibody, Leu-3a+3b, showed weak positive staining of most infiltrating cells. However, there were no reactions with antisera to Leu-6, Leu-7, Leu-14, CALLA, OKT 6, OKT 8, OKT 16, OKB 19, OKM 14, beta F1, or delta TCS1. OKM 5-positive keratinocytes were observed in some parts of the upper epidermis, although no OKM 5 expression could be detected on any tumor cells. Cytochemistry, immunohistochemistry, and electron microscopy can aid in the diagnosis of monocytic leukemia. This case illustrates the importance of using an expanded panel of monoclonal antisera in certain hematopoietic tumors.     

Congenital Leukemia Cutis Preceding Monoblastic Leukemia by 3 Months

Abstract: We report an infant born with a cutaneous nodular eruption and neutropenia. Skin biopsy specimens revealed an immature dermal infiltrate suggestive of leukemia cutis, but repeated peripheral blood and bone marrow examinations failed to demonstrate malignant cells. The eruption resolved spontaneously. At the age of 3 months, a second occurrence of maculopapular skin lesions led to discovery of an acute monoblastic leukemia with (9;11)(p21–22;q23) translocation. Congenital acute leukemia is a rare disease associated with skin infiltration in 25% to 30% of patients. Usually the diagnosis is easily made by peripheral blood examination and/or bone marrow aspirate. However, skin involvement may precede acute leukemia by several weeks. Although very rare, this event must be kept in mind.     

A Rare Lymphoma in a Patient with Amyopathic Dermatomyositis

A 37-year-old Caucasian woman was evaluated for a photosensitive dermatitis. A positive anti-nuclear antibody with a titer of 1 : 1280 and a speckled pattern was noted and she was diagnosed with subacute cutaneous lupus erythematosus (SCLE). Although the initial dermatologic diagnosis was SCLE, a skin biopsy suggested the additional possibility of dermatomyositis because of increased dermal mucin. We began following her at the request of the dermatology department, and a diagnosis of amyopathic dermatomyositis was made based on the lack of objective muscle weakness, normal muscle enzymes, negative double-stranded DNA, SSA/SSB, and RNP/Smith antibody panel, and especially on the cutaneous examination findings. A malignancy evaluation included a normal CT scan of her chest, abdomen, and pelvis, esophagogastroduodenoscopy, colonoscopy, mammography, pelvic ultrasound, Papanicolaou smear, and endometrial biopsy. She developed vaginal bleeding 1 year after the onset of her skin manifestations. Repeat gynecologic evaluation, including cervical biopsy, revealed a large B-cell cervical lymphoma. Amyopathic dermatomyositis and lymphoma of the cervix are both rare conditions. Our case emphasizes the importance of considering underlying malignancy at the time of diagnosis and while the patient is followed clinically. Additionally, the clinician must remain vigilant in evaluating any new clinical changes in follow-up care. To our knowledge, this is the first documented case of lymphoma of the cervix in the setting of amyopathic dermatomyositis.     

Exfracorporeal Photochemotherapy in the Treatment of Cutaneous T-Cell Lymphoma

The term cutaneous T-cell lymphoma (CTCL) encompasses the spectrum of diseases characterized by a monoclonal proliferation of malignant T lymphocytes predominantly of the mature T-helper cell type. These include mycosis fungoides, which is usually localized to the skin for many years, and the Sezary syndrome, the leukemic variant in which characteristic, bizarre lymphatic cells with deeply indented or cerebriform nuclei, the Sezary cells, infiltrate lymph glands and internal organs such as the spleen, liver, lungs, heart, and bone marrow. The condition is more common in men after their fourth decade. The treatment of CTCL varies depending on the stage of the disease. The skin of the patient is the primary index of effectiveness of therapy. Options range from topical steroids, topical nitrogen mustard, X-irradiation, electron beam irradiation, and 8-methoxypsoralen (8-MOP) combined with ultraviolet A photochemotherapy (PUVA), to leukapheresis and systemic chemotherapy. More recently, extracorporeal photochemotherapy (ECPC) has been introduced. The safety and efficacy of this modality is further investigated in six patients who fulfilled the criteria of diagnosis of CTCL. The problems encountered in objectively evaluating the clinical responses in the patients are outlined and improvements in the protocol to overcome these are suggested. The proposed mechanism of action is an immunostimulatory one and a procedure that is relatively free from side effects; it offers promise as a potential treatment for a difficult cancer.     

Predominant cutaneous infiltration by OKT6- and OKT8-positive cells in a case of Sézary syndrome

Summary Using an immunoperoxidase (skin biopsy) and an immunofluorescence (peripheral blood, bone marrow punctate) technique, and monoclonal antibodies raised against peripheral mature lymphocytes, T helper subsets, T suppressor subsets, and Langerhans cells, we found a predominant dermal infiltration with lymphocytes of the suppressor phenotype and a predominant epidermal infiltration with Langerhans cells in a patient with Sézary syndrome (cutaneous T-cell lymphoma, CTCL). Repeated peripheral blood examinations showed an increased percentage of lymphocytes of the helper phenotype. A bone marrow examination revealed a ratio of suppressor/helper subsets of 1:4. The findings in the skin seem to be inconsistent with most of the results of previous studies in patients with CTCL; the significance of these findings is discussed.This study was partly supported by the Deutsche Forschungsgemeinschaft, Grant no. Lo 285/2-1This work is dedicated to Prof. Th. Nasemann on occasion of his 60th birthday     

Erythema nodosum and granulomatous lesions preceding acute myelomonocytic leukemia

A 65-year-old female with a one-month history of painful eruptions on her lower extremities was admitted to our hospital. Histological examination revealed erythema nodosum (EN), and the patient was treated with oral prednisolone (PSL; 20 mg daily). The eruptions subsided in two weeks. One month later, painful reddish eruptions recurred on her upper limbs and abdomen in addition to her lower extremities. A skin biopsy from an abdominal erythematous plaque revealed a non-caseating granuloma without microorganisms or foreign-body materials. These eruptions also disappeared with treatment with oral PSL (20 mg daily). No underlying disease, including sarcoidosis, diabetes mellitus, or rheumatoid arthritis, was found. However, five months later, the patient developed conspicuous leukocytosis. She was diagnosed with acute myelomonocytic leukemia (M4) and treated with chemotherapy. After complete remission had been achieved, the EN reappeared, in association with an increase in blastic cells in the bone marrow. Serum levels of tumor necrosis factor-alpha and interleukin-1 beta, which are thought to be essential for granuloma formation and induction of EN, were markedly elevated. Physicians must remember that recurrent EN and granulomatous lesions can be a prodromal sign of leukemia.     

Aleukemic leukemia cutis: juvenile chronic granulocytic leukemia presenting with figurate cutaneous lesions

We report a 3 1/2-year-old girl who developed a figurate cutaneous eruption. Distinctive findings in her skin biopsies, as well as unusual red cell characteristics, in the presence of a normal peripheral smear and bone marrow biopsy, led us to suspect the diagnosis of preleukemic juvenile type chronic granulocytic leukemia. This is the first case we know of in which this diagnosis was suspected prior to abnormal findings in the peripheral smear or bone marrow.     

Extramedullary (skin) presentation of acute monocytic leukemia resembling cutaneous lymphoma: morphological and immunulogical features

Acute monocytic leukemia has been noted to exhibit a predilection for extramedullary involvement (gums, skin, and lymph nodes) at presentation. More unusual is the occurrence in an extramedullary site in the absence of bone marrow involvement. A case is reported with initial presentation in skin preceding a subsequent evolution to a leukemic phase by one year. The skin tumor was initially diagnosed and treated as a lymphoma. A second skin tumor, biopsied one year later was immunophenotyped as a T cell lymphoma using a screening panel of antisera (OKT4 positive, OKMI negative). Shortly thereafter a monocytic leukemia (M5) was discovered. Using a larger panel of antisera and enzyme markers on the second skin biopsy confirmed the monocytic rather than lymphocytic nature of the skin tumor. This case illustrates the importance of using an expanded panel of monoclonal antisera in certain hematopoietic tumors.     

Remarkable remission of a follicular lymphoma treated with rituximab and polychemotherapy (CHOP)

We describe a 50-year-old female patient who developed extensive lymphomatous infiltrates on her forehead, scalp and face within a few months. Histology and immunohistochemistry of skin tumours revealed a CD20 positive follicular B-cell lymphoma. Subsequently, extracutaneous manifestations were detected by computed tomography scans and bone marrow biopsy. The patient suffered from a primary nodular malignant lymphoma with extraordinary cutaneous infiltration of the head. Therefore, combination treatment with a monoclonal antibody against the CD20 antigen, rituximab, and polychemotherapy (CHOP scheme) was administered every 3 weeks. After the second course of treatment a complete regression of cutaneous infiltrates was noticed. Follow-up biopsies on the forehead showed no evidence of CD20 positive lymphoma cells, now. Despite mild leucocytopaenia therapy was well tolerated.     

Chloroma (aleukaemic leukaemia cutis) initially diagnosed as cutaneous lymphoma

A 65-year-old man presented in 1997 with a nodule on his back; histology showed apparent high grade T-cell lymphoma, treated after excision with radiotherapy. He relapsed with lesions on the thigh and buttock in 1998 and was treated with CHOP chemotherapy with a complete response. Further relapse occurred in 1999 with a nodule on his thigh again; he received CNOP (doxorubicin substituted with mitozantrone). At no stage was there clinical, bone marrow or radiological evidence of extra cutaneous disease. In November 2000 he presented with widespread indurated plaques and violaceous nodules. Biopsies repeated with extensive immunohistological staining diagnosed aleukaemic leukaemia cutis. Our patient was diagnosed with cutaneous T-cell lymphoma (CTCL) on the basis of clinical and haemotoxylin & eosin appearances. The correct diagnosis was made after extensive immunohistological studies (including myeloid markers) of repeat biopsies. This case illustrates the importance of diagnostic review in atypical CTCL. There is a high incidence of progression to acute myeloid leukaemia.     

A trial of fludarabine and cyclophosphamide combination chemotherapy in the treatment of advanced refractory primary cutaneous T-cell lymphoma

BACKGROUND: The combination of fludarabine and cyclophosphamide shows synergistic toxicity in vitro and has been used to treat nodal non-Hodgkin's lymphoma and relapsed chronic lymphocytic leukaemia. OBJECTIVES: To test the efficacy of this combination in 12 patients with cutaneous T-cell lymphoma (CTCL). METHODS: Nine patients with erythrodermic CTCL were identified for the study, eight of whom met the criteria for Sézary syndrome (SS), and three with tumour-stage mycosis fungoides (MF). Patients received intravenous fludarabine and cyclophosphamide 3 days monthly for 3-6 months. RESULTS: Six patients tolerated at least three cycles. Five with SS had a response (one had a complete clinical response and four a partial response) and one patient with MF had stable disease. The mean duration of the response was 10 months. Six patients had treatment withdrawn, five due to bone marrow suppression and one due to progressive disease. No difference in pretrial parameters were found in those who had treatment withdrawn and those who tolerated at least three courses. Survival since the trial was similar in both groups at 11 months. CONCLUSIONS: These data indicate that the combination of fludarabine with cyclophosphamide may be of clinical benefit in patients with SS but does not affect patient survival. As with other multiagent chemotherapy regimens, bone marrow toxicity is a common and severe side-effect. These data suggest that this regimen should be considered palliative and should be reserved for patients with refractory disease without bone marrow suppression.     

Aleukemic leukemia cutis

A 46-year-old man presented with nodular skin lesions, a biopsy specimen of which demonstrated a poorly differentiated malignancy. Touch preparations with histochemical staining and electron microscopy confirmed leukemia cutis. Results from a bone marrow aspirate disclosed focal areas of increased myeloblasts, and cytogenetic analysis revealed an abnormal karyotype as follows 46,XY, t(1;2) (q44p13). Antileukemic therapy resulted in prompt disappearance of the skin nodules, and a return of the patient's bone marrow to normal was noted, but after six months of intensive chemotherapy leukemia cutis recurred without morphologically identifiable leukemia in the bone marrow. The patient underwent successful bone marrow transplantation from an HLA-identical sibling but died 70 days after the transplant from disseminated aspergillosis.     

Lymphomatoid granulomatosis

The clinical and pathologic appearance of seven patients with lymphomatoid granulomatosis who had skin lesions when first seen is reviewed. Six patients subsequently developed systemic disease. Although the gross morphology of the skin lesions is variable, the pathology is distinctive. An adequate deep biopsy shows the characteristic lymphohistiocytic infiltrate with variable numbers of atypical cells. Angiodestruction is less evident in the skin compared to other organs. The infiltrate surrounds and invades not only vessels but also nerves and epidermal appendages. The skin biopsy specimen can be differentiated from the lymphomatous infiltrates and Wegener's granulomatosis. Two of the patients who developed systemic disease were diagnosed by skin biopsy but clinicians failed to institute therapy, preferring to wait for other organ involvement. In addition, two patients developed lymphoma, one of which was confirmed at autopsy and one on subcutaneous and bone marrow biopsy 5 years after the initial skin diagnosis. Lymphomatoid granulomatosis can be diagnosed by performing a skin biopsy. Appropriate chemotherapy may result in a high percentage of complete remissions and therefore the dermatopathologist can play an important role in the early diagnosis of this potentially fatal disease.     

A case of subcutaneous panniculitis-like T-cell lymphoma with haemophagocytosis developing secondary to chemotherapy

A 45-year-old woman presented with fever, generalized skin lesions and multiple lymphadenopathies. In her past history she had had six courses of cyclophosphamide and cisplatin combination chemotherapy 7 years ago because of an ovarian carcinoma. We found pancytopenia in the peripheral blood examination. Skin biopsy showed diffuse subcutaneous infiltration reminiscent of panniculitis but composed of malignant lymphoid cells that were of T lineage. Bone marrow biopsy showed normocellular myeloid tissue with abundant haemophagocytic macrophages. Subcutaneous panniculitis-like T-cell lymphoma with haemophagocytic syndrome was diagnosed. This is the first case reported of subcutaneous panniculitis-like lymphoma occurring secondary to chemotherapy.