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Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii
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Letter to the Editor

Clinical manifestations of diffuse large B‑cell lymphoma in the skin and subcutaneous tissue a case series study

Katarzyna Dulik
1
,
Grażyna Kamińska-Winciorek
1
,
Ryszard Swoboda
1
,
Anna Kwiatkowska-Pamula
1
,
Sebastian Giebel
1

1.
Department of Bone Marrow Transplantation and Oncohematology, Maria Sk³odowska-Curie National Research Institute of Oncology (MSCNRIO), Gliwice Branch, Gliwice, Poland
Adv Dermatol Allergol 2020; XXXVII (5): 812-816
Online publish date: 2020/11/07
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Diffuse large Bcell lymphoma (DLBCL) is the most common subgroup of nonHodgkin lymphoma, accounting for 30% to 40% of cases [1]. The most common symptom is lymphadenopathy (about 70%) or involvement of other organs (30%), including the gastrointestinal tract, skin and soft tissue, urogenital system, bones, respiratory system, thyroid, salivary gland, and breast. The presence of extranodal lesions is associated with a worse prognosis [2].
The paper presents 4 patients diagnosed with DLBCL with secondary involvement of the skin and subcutaneous tissue, treated at the Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie National Research Institute of Oncology in 2017. In all cases the diagnosis was made on the basis of histopathologic examination with immunophenotyping of tumour sections from the internal organs, skin and subcutaneous tissue, and lymph nodes, affected by the disease process. Case 1: A 68yearold female patient with follicular lymphoma (FL) G2 diagnosed in April 2014 on the basis of histopathological examination of abdominal tumour located between the intestinal loops and the rectus abdominis muscle. Because of two disease relapses, the patient was treated with chemotherapy and radiotherapy, each time with a complete remission assessed by computed tomography. In March 2017, extensive oedema involving the skin and subcutaneous tissue appeared in the upper half of the right thigh, also affecting the right inguinal region. Despite the use of bendamustine monotherapy, there was rapid progression of isolated infiltrative lesions in the skin and subcutaneous tissue, initially located in the right thigh (Figure 1 A), with subsequent hard infiltration on erythematous background, and numerous blisters with formation of ulcerations covered with bloody crusts (Figures 1 B, C), which was confirmed by computed tomography. The fifth line of treatment was administered according to the RDHAP regimen (rituximab, cisplatin, cytarabine arabinoside, dexamethasone). Histopathological examination with immunophenotyping of cutaneous and subcutaneous tissue revealed transformation of FL to DLBCL, with BCL2/cMyc expression, corresponding to doubleexpressor lymphoma. The therapy used in this patient (four RDHAP cycles) resulted in a significant reduction of tumour mass in the right thigh, with complete resolution of skin lesions (Figure 1 D). Unfortunately, during the preparation for bone marrow autotransplantation, there was a rapid recurrence in the form of massive infiltration in the right thigh and general symptoms of the disease. The patient died shortly afterwards.
Case 2: A 66yearold female patient with oedema of the right lower limb that had increased for 1 year. Computed tomography examination of the abdomen and pelvis revealed extensive nodular infiltration in the lower abdomen and pelvis, soft tissue infiltration from the right groin to the right popliteal fossa along the adductor muscles of the medial part of the thigh. Histopathological examination with immunophenotyping of tumour in the right thigh confirmed the diagnosis of DLBCL (CD20+, BCL6-, BCL2+, MUM1+, Cyclin D1, CD3-, Ki67 about 90%). Chemotherapy according to the RCHOP regimen (rituximab, doxorubicin, vincristine, cyclophosphamide, prednisone) was administered. During this treatment, disease progression occurred with massive growth of a tumour within the subcutaneous tissue of the right thigh, up to 15 × 10 cm in diameter, with increasing oedema of the right lower limb (Figure 1 E) and a tumour infiltrating the skin and subcutaneous tissue in the left shoulder joint, measuring 10 × 10 cm in diameter (Figure 1 F). Dermoscopy showed the presence of numerous telangiectasias (Figure 1 G). The second line of treatment was followed by shortterm CR of the new nodular lesions and partial remission of tumour in the right thigh. Despite 2 cycles of chemotherapy, tumour in the right thigh progressed with increasing swelling of the whole right lower limb. The third line of treatment was administered according to the BGD regimen (bendamustine, gemcitabine, dexamethasone) with simultaneous irradiation of this lesion, without any tumour regression. In addition, new infiltrative lesions occurred in the skin and subcutaneous tissue of the abdomen (Figure 1 H).
Case 3: An 86yearold female patient with DLBCL lymphoma (CD20+, CD3-, cyclin D1-, Ki67 about 50%) in the left nasal cavity, diagnosed in 2012. She had been previously treated with 6 cycles of the RCOP regimen (rituximab, cyclophosphamide, vincristine, prednisone) with subsequent radical radiotherapy for residual lesions (total dose 45 Gy), and the patient achieved the complete remission. In 2017, a rapidly growing hard infiltrative lesion of the right lower eyelid with accompanying oedema and infiltration in the suborbital region (Figure 2 A) and in the right parotid salivary gland area were found. Due to the rapidly progressing disease, oral prednisone 1 mg/kg was included, followed by RCOP chemotherapy with disease remission (Figure 2 B). The dermoscopic picture of the right lower eyelid lesion after the treatment showed a significant reduction in the number and thickness of serpentineshaped and arborising blood vessels in the examined area (Figures 2 C, D).
Case 4: A 60yearold female patient treated in April 2018 because of a rapidly growing tumour of the left frontal area and the left mandibular angle, without general symptoms (Figure 2 E), preceded by cervical lymphadenopathy persisting since August 2017. In February 2018, based on histopathological examination of a lymph node specimen from the left submandibular region, FL G3B (follicular pattern) was diagnosed with the following immunophenotype: CD20+, BCL2+, BCL6+, CD21+, CD30-/+, CD10-, MUM1-, CD3-, CD5-, CD23, MYC-, Cyclin D1-, CD138-, Ki67 proliferative activity up to 90–95%, with suspected transformation to DLBCL. Positron emission tomography/computed tomography scan showed active neoplastic lesions in the head and neck. The patient received RCHOP treatment with partial remission of tumour in the left supraorbital area and lymph node lesions (Figure 2 F).
NonHodgkin lymphomas are neoplasms of the lymphatic system originating from the lymphoid cells of the B, T and NK cell lines. The most common subtype is DLBCL, which is often associated with extranodal lesions [3]. The most commonly affected organs include the gastrointestinal tract and the skin [4]. Secondary involvement of the skin occurs in approximately 25% of all skin lymphomas, of which 65% originate from B cells (26% of these cases are DLBCL and 21% are FL) [5]. Despite similar morphology, secondary lymphomas of the skin differ from primary lesions in terms of course, method of treatment, and prognosis [6]. Primary Bcell lymphomas of the skin have a milder course, while secondary lymphomas have a worse prognosis and are usually resistant to chemotherapy [7, 8]. The primary DLBCL leg type represents approximately 5–10% of the B-cell cutaneous lymphomas. Skin lesions occurred as single, multiple, and even grouped [9]. Our own case series’ study reveals that the clinical picture of presented Bcell lymphomas with secondary involvement of the skin is characterised by rapidly growing, nonpruritic nodular or extensive infiltrative lesions. It is therefore extremely important to know the clinical picture of lymphomas, and close monitoring and cooperation between an oncohaematologist, dermatologist and pathologist are necessary in order to implement the proper diagnostic and therapeutic management. Immunophenotyping has a diagnostic value in differentiating of the lymphoma subtypes [10], but does not always coincide with molecular studies (FISH). The most common cytogenetic changes in DLBCL concern BCL6 (30–40%), BCL2 (15–30%) and MYC (5–10%). In a small percentage of cases these features may coexist, e.g. BCL2 and cMyc (“double hit”), or additionally with BCL6 (“triple hit”) [11]. These subtypes are commonly associated with extranodal lesions and resistance to treatment [12]. Patients with DLBCL lymphoma that is recurrent or resistant to immunochemotherapy have a poor prognosis [2].
Dermoscopic assessment may be helpful not only in the recognition of primary cutaneous B-cell lymphomas [13], but could be also implemented as a non-invasive diagnostic and monitoring tool for B-cell lymphomas with the secondary skin involvement [14]. Presented cases of nonHodgkin lymphoma of the DLBCL type were characterized by their rapid progression and relapses, extensive secondary skin and subcutaneous tissue involvement, poor response to therapeutic regimens with the final bad prognosis. So far, only single cases of primary nonHodgkin lymphoma with secondary involvement of the skin and soft tissues have been reported in the literature [4, 15]. Treatment of this group of patients includes immunochemotherapy, new drugs, symptomatic treatment, and consolidation with allogeneic haematopoietic cell transplantation in selected cases.
Skin involvement in the course of lymphoma may be primary or secondary. It is worth noting that lymphomas with secondary involvement of the skin have a worse prognosis and are usually resistant to chemotherapy, which was unfortunately confirmed in the presented patients.

Acknowledgments
Katarzyna Dulik and Gra¿yna Kamiñska-Winciorek participated equally in the development of this paper.

Conflict of interest
The authors declare no conflict of interest.
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