Two cases of merkel cell tumour arising in patients with chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) has been associated with an increased incidence of second neoplasms, especially skin cancers such as basal and squamous cell carcinomas. No association with the rarer skin cancer, the Merkel cell tumour (MCT), has previously been reported. Two patients with MCT had a previous diagnosis of CLL. MCT is an aggressive skin cancer, as up to 45% of patients have lymph node involvement at presentation and 5-year disease-free survival is as low as 30%. It is most commonly found on sun-exposed areas of the body, and ultraviolet radiation together with drug-induced or CLL-induced immunosuppression may be the underlying mechanism in the observed relationship between CLL and other skin cancers.     

Eosinophilic spongiosis in association with bullous pemphigoid and chronic lymphocytic leukaemia

We report the onset of an unusual blistering eruption following a diagnosis of B-cell chronic lymphocytic leukaemia (CLL). The histology consistently showed eosinophilic spongiosis, but the diagnosis of bullous pemphigoid was only confirmed after 13 years by repeated immunofluorescence studies. The occurrence of subepidermal blistering diseases in association with B-cell lymphoproliferative disorders is rare; a recent study showed that the majority of these cases are epidermolysis bullosa acquisita, confirmed by immunological studies. Only two cases of immunofluorescence-proven bullous pemphigoid in association with CLL have been previously reported.     

Successful treatment of leukaemia cutis with cladribine in a patient with B-cell chronic lymphocytic leukaemia

Cutaneous presentation of B-cell chronic lymphocytic leukaemia (B-CLL) is uncommon, and the influence of skin changes on B-CLL prognosis is unclear. We report a patient with B-CLL Rai II, with multiple nodular skin infiltrations on the trunk, upper arms and thighs as well as constitutional symptoms, who was successfully treated with cladribine. The peripheral blood (PB) lymphocytes were CD19, CD20, CD23 and CD5 positive, which confirmed the diagnosis of B-CLL. Skin biopsy of one of the lesions showed an intense infiltrate composed of small lymphocytes with no epidermotropism. These cells also showed the expression of CD19, CD20, CD23 and CD5 antigens similar to those presented on PB lymphocytes. Polymerase chain reaction performed on bone marrow lymphocytes and a lesional skin biopsy using consensus primers for immunoglobulin heavy-chain genes also showed the same monoclonal population of B lymphocytes both in the bone marrow and in the skin. The patient received four courses of cladribine 0.12 mg kg-1 daily as a 2-h infusion for five consecutive days. The courses were repeated at monthly intervals. The lymphocytosis gradually decreased and the PB count normalized after three courses. At the same time, a significant decrease in the cutaneous symptoms was observed. The patient became free of skin tumours after the fourth course of cladribine; only slight discoloration at the previous sites of cutaneous infiltration remained. There was no relapse of leukaemia cutis during a further 7 months of observation.     

Paraneoplastic pemphigus. A report of two cases associated with chronic B-cell lymphocytic leukaemia

Paraneoplastic pemphigus (PNP) is an autoimmune blistering and erosive mucocutaneous disease associated with neoplasia. Clinical manifestations are polymorphous, and include erythema, bullae, erythema multiforme-like lesions and severe mucous membrane involvement. PNP manifesting as lichenoid dermatitis has recently been observed. We describe two Italian men with fatal PNP featuring typical PNP autoantigens associated with chronic B-cell lymphocytic leukaemia. The first patient presented with an extensive blistering eruption, several erythema multiforme-like lesions and severe mucosal involvement. The second patient presented with a lichenoid dermatitis, then developed bullae, and died with an erythrodermic and exfoliative dermatosis resembling pemphigus foliaceus. Our patients represent two Italian cases of well-documented PNP. In patient 2, the sequence of clinical presentations was unique, and strongly supports the hypothesis of epitope spreading through chronic lichenoid inflammation of the dermo-epidermal junction exposing new self antigens, leading to the humoral response characteristic of PNP.     

皮肤淋巴细胞浸润症

报告1例皮肤淋巴细胞浸润症.患者女,41岁.因左鼻翼皮肤红色斑疹半年来我院门诊就诊,既往曾多次被诊断为"毛囊炎"、"痤疮"等,但治疗效果欠佳.皮损组织病理检查:真皮中、深层血管及皮肤附属器周围可见以淋巴细胞为主的带状浸润.免疫组化染色:CD68(+)、CD3(+++)、CD45RO(+++)、CD20(+)及CD79a(-).根据临床表现及组织病理检查结果,诊断为皮肤淋巴细胞浸润症.     

Richter syndrome first manifesting as cutaneous B-cell lymphoma clonally distinct from primary B-cell chronic lymphocytic leukaemia

Richter syndrome (RS) is a transformation to high-grade non-Hodgkin lymphoma in patients with chronic lymphocytic leukaemia (CLL). RS may develop in lymph nodes or rarely extranodally. Skin localization of RS has been described in only a few cases. We present a 77-year-old woman who developed isolated diffuse large B-cell lymphoma (LBCL) in the skin of the nose without any other symptoms of RS. The LBCL in the skin was clonally distinct from the original bone marrow CLL cells. Moreover, LBCL cells were positive for LMP-1 segment of Epstein-Barr virus and overexpressed p53 protein. The patient was successfully treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) and adjuvant local radiotherapy.     

Cutaneous adverse reaction to 2-chlorodeoxyadenosine with histological flame figures in patients with chronic lymphocytic leukaemia

INTRODUCTION: 2-Chlorodeoxyadenosine (cladribine or 2-CdA) is a purine analogue that has been used successfully in hairy cell leukaemia (HCL). Moreover, it has been increasingly used to treat chronic lymphoproliferative syndromes and paediatric acute myeloid leukaemia. Cutaneous side-effects associated with this drug have seldom been described in cases of HCL. PATIENTS AND METHODS: We describe three patients with chronic lymphocytic leukaemia that presented generalized skin eruptions after treatment with 2-CdA. RESULTS: All patients had advanced disease, receiving 2-CdA as a second or third line chemotherapy. Skin lesions were severe and chemotherapy had to be discontinued. Histological examination of skin biopsies showed an eosinophil-rich infiltrate with flame figures, similar to what is observed in Wells' syndrome (eosinophilic cellulitis). Corticosteroids were effective to control the eruptions. CONCLUSIONS: Cutaneous adverse reactions associated with 2-CdA have seldom been observed in the treatment of HCL. However, as this purine analogue has been used in more advanced cases these may be more frequent and severe. The pathophysiology of these lesions is unclear, but it is probably related to drug-induced change in T-cell imbalance in severely immunosuppressed patients.     

呈环状损害的皮肤淋巴细胞浸润症

报告1例呈环状损害的皮肤淋巴细胞浸润症.患者男,82岁.因右耳上发际内环形紫红色浸润性斑块半年就诊.皮损组织病理检查示表皮轻度角化,颗粒层、棘层增厚,棘细胞间轻度水肿,细胞外移,真皮浅层大量以致密淋巴细胞为主的带状浸润.免疫组化染色结果示:CD3、CD20、CD79、S-100蛋白均( ).CDl92、CD43均(±).     

Mycosis fungoides and chronic lymphocytic leukaemia--composite T-cell and B-cell lymphomas presenting in the skin

Composite lymphomas involving cutaneous B-cell and T-cell lymphomas are very uncommon. We report here the unique circumstance of a patient with mycosis fungoides (primary cutaneous T-cell lymphoma) who later developed chronic lymphocytic leukaemia (B-cell lymphoproliferation, B-CLL), which presented in the skin (leukaemia cutis) as a composite lymphoma affecting an earlobe. The presence of both lymphoproliferative disorders was confirmed with immunophenotyping and the finding of both immunoglobulin gene rearrangements and T-cell receptor gene rearrangements in the ear and the same T-cell receptor gene rearrangement in a plaque lesion of mycosis fungoides on the arm.     

伴有皮肤表现的慢性B淋巴细胞白血病

报告1例伴有特异性和非特异性皮损的慢性B淋巴细胞白血病.患者男,66岁.临床表现为全身广泛淋巴结增大;躯干及四肢出现红斑、丘疹、坏死;左耳郭有浸润性肿块.皮损组织病理检查示左耳郭皮损为淋巴细胞白血病皮肤浸润,其余皮损为血管周围炎及脂膜炎改变.经淋巴结组织病理、骨髓细胞学、骨髓组织病理及流式细胞仪检测诊断为慢性B淋巴细胞白血病.     

Hypereosinophilic dermatitis-like erythema annulare centrifugum in a patient with chronic lymphocytic leukaemia

A 65-year-old male presented with a history of disseminated erythema annulare centrifugum lesions and a high peripheral blood eosinophilia (55%). Histopathology of a lesion revealed a superficial and deep perivascular and interstitial inflammatory eosinophilic infiltrate. The bone marrow aspirate showed a heavy eosinophilic infiltrate. There was no evidence of any other systemic involvement except for bone marrow eosinophilia. The patient had a 6-year history of chronic lymphocytic leukaemia. The disease is in complete remission for the last 3 years. The clinical and histopathological findings in the reported patient correspond to the diagnosis of hypereosinophilic dermatitis. Topical treatment with corticosteroid creams was successful. The cutaneous lesions gradually resolved in 8 weeks, within 7 months the peripheral blood eosinophilia slowly declined from 55% to 7%.     

Primary cutaneous marginal zone B-cell lymphoma in a patient with chronic lymphocytic leukaemia

Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is a low-grade malignant lymphoma that presents in the skin with no evidence of extracutaneous localization at diagnosis. We present an 80-year-old woman with B-cell chronic lymphocytic leukaemia (CLL) who developed multifocal PCMZL lesions 14 months after CLL diagnosis. PCMZL was clonally similar to the original bone marrow (BM) CLL cells. The specific translocation t(14;18) (q32;q21) with breakpoints in IGH and BCL2 loci was found in a skin specimen, but was absent in BM and peripheral blood (PB) cells. In contrast, a 13q deletion was found in BM and PB CLL cells. The patient was treated with chlorambucil and complete response of PCMZL was achieved. To our knowledge this is the first patient with CLL in whom PCMZL has been diagnosed.     

Activated and cycling lymphocytes in benign dermal lymphocytic infiltrates including psoriatic skin lesions

Summary Single-cell DNA measurements obtained using flow cytometry have previously been used as a diagnostic tool for various malignant diseases. We used this technique to characterize the dermal infiltrates of 14 patients with psoriatic skin lesions and 22 patients with various benign skin disorders. The DNA histograms of all of the patients exhibited an increased number of cells showing propidium-iodide fluorescence in the hyperdiploid region as compared to those seen in control DNA histograms of normal blood mononuclear cells. The calculated DNA indices revealed one hyperdiploid (G₀/G₁) peak in 17 cases and two hyperdiploid (G₀/G₁) peaks in 13 cases. The results suggest that the dermal lymphocytic infiltrate consists of (1) lymphocytes in the cell-division cycle, (2) non-cycling lymphocytes (G₀) and (3) activated lymphocytes that may either remain in a non-cycling state or enter the cell cycle.     

皮肤淋巴细胞浸润症1例

报告1例皮肤淋巴细胞浸润症。患者男，32岁。面部出现红色斑块2年，胸部、背部、四肢出现类似皮损1年。组织病理示皮肤淋巴细胞浸润症。经氯喹等药物治疗，皮损好转。目前仍在随访中。     

Spindle cell melanoma coexisting with chronic lymphocytic leukemia/small lymphocytic lymphoma: a rare collision tumor in multiple sites

A strong association has been reported between chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) and malignant melanoma (MM). In rare cases of MM, lymphoid malignancies may be detected incidentally during sentinel lymph node biopsies. In this case, we found a unique collision of MM and CLL infiltration in the skin. An 88-year-old male patient presented with a mass on the nasal root. Histopathological examination of the skin biopsy specimen revealed a deeply infiltrative, atypical spindle cell proliferation in the background of a collagenous stroma. Accompanying this lesion, there were foci of monotonous lymphoid cell populations involving skin appendages. In the immunohistochemical studies, the spindle cells were diffusely positive for S100, and focally positive for Melan-A and HMB45; the lymphoid cells were positive for CD20, CD5, and Bcl-2 and negative for CD3, Bcl-6, CD10, and Cyclin D1. Histopathological and immunohistochemical findings were consistent with diagnoses of spindle cell melanoma and CLL. Interestingly, these two tumors together in their same morphological appearance were confirmed in a subsequent liver biopsy. Active skin surveillance of patients with CLL may be important to detect MM at an early stage that correlates with a better prognosis.     

Concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma in a patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma

The phenomenon of histiocytic/dendritic cell sarcomas arising through transformation of a pre-existed lymphoproliferative disease is called transdifferentiation. Langerhans cell sarcoma transdifferentiating from chronic lymphocytic leukemia/small lymphocytic lymphoma is extremely rare and all the reported cases were localized in lymph nodes. We present a case of concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, in which the chronic lymphocytic leukemia/small lymphocytic lymphoma preceded the development of the Langerhans cell sarcoma. A cutaneous lesion from a 63-year-old patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma was biopsied. The histologic examination revealed a mixture of two cell populations infiltrating diffusely the dermis. The first was composed of small lymphoid cells with somewhat monotonous appearance and mild nuclear atypia positive for PAX5, CD79a, CD20, CD23, CD5, and LEF1. The second was composed of large cells with abundant cytoplasm and pleomorphic nuclei. These cells were positive for CD1a, CD207, and S100 protein and exhibited a high mitotic rate and a high MIB-1 immunostaining index. Therefore, two different entities, chronic lymphocytic leukemia/small lymphocytic lymphoma and Langerhans cell sarcoma, were detected in the same skin fragment. The patient died 3 years after initial diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma.     

The lymphocytic infiltrates in the ear-Lobe skin of diabetics

Summary In 1953 Jessner and Kanoff described a special type of infiltration of the skin. Later, similar findings were described as an accompanying phenomenon in different diseases and as a reaction to variable factors. There are as yet no data about these infiltrates in connection with diabetes.In this investigation the material from 117 human ear-lobes (26 healthy and 91 diabetics, all aged between 20–45 years) was histologically analyzed. It was established that lymphocytic infiltrates were present in 2/3 of the diabetic patients and less than half of the healthy persons. The difference between these groups of persons was statistically significant.Accordingly it can be said, that a sort of Jessner-Kanoff infiltrate can also be seen in the ear-lobe skin of diabetics, and that this method could be applicable as an additional method for diagnosing diabetes.

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Zusammenfassung 1953 beschrieben Jessner und Kanoff bekanntlich eine besondere Form von Hautinfiltration, die später auch als Begleiterscheinung bei verschiedenen Erkrankungen und als Reaktion auf verschiedene Ursachen gesehen wurde. Beobachtungen über eine Verbindung mit Diabetes mellitus liegen bislang nicht vor.In der jetzigen Studie wurde Excisionsmaterial von 117 menschlichen Ohrläppchen (26 gesunde Personen und 91 Patienten mit Diabetes mellitus, Gesamtalter 20–45 Jahre) histologisch untersucht. Lymphocytäre Infiltrationen lagen bei zwei Drittel der Diabetes-Patienten und in weniger als der Hälfte der gesunden Kontrollpersonen vor. Der Unterschied zwischen den beiden Gruppen ist statistisch signifikant.Es zeigt sich damit, daß Jessner-Kanoff'sche Infiltrate auch in den Ohrläppchen von Patienten mit Diabetes mellitus gefunden werden können und daß diese Beobachtung als ein weiteres Hilfsmittel für die Diagnostik eines Diabetes mellitus herangezogen werden kann.