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  Table of Contents    
CASE REPORT  
Year : 2019  |  Volume : 62  |  Issue : 3  |  Page : 470-472
A rare case of primary cutaneous diffuse large B-cell lymphoma, leg type in a patient with chronic lymphedema of the leg


1 Department of Pathology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, India
2 Institute of Applied Dermatology, Kasargod, Kerala, India
3 Mediclu Diagnostics, Bengaluru, Karnataka, India

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Date of Web Publication26-Jul-2019
 

   Abstract 


A rare complication of chronic lymphedema is development of cutaneous malignant tumors particularly cutaneous lymphomas. We report a case of primary cutaneous diffuse large B-cell lymphoma, leg type, associated with chronic lymphedema of the lower limbs. A literature review identified 12 additional cases of primary cutaneous lymphomas associated with chronic lymphedema. Chronic lymphatic stasis may cause a local dysfunction of the immune system that predisposes to the induction of neoplasia, cutaneous lymphomas in particular.

Keywords: Leg type, lymphedema, lymphoma

How to cite this article:
Vijaya B, Narahari SR, Shruthi MK, Aggithaaya G. A rare case of primary cutaneous diffuse large B-cell lymphoma, leg type in a patient with chronic lymphedema of the leg. Indian J Pathol Microbiol 2019;62:470-2

How to cite this URL:
Vijaya B, Narahari SR, Shruthi MK, Aggithaaya G. A rare case of primary cutaneous diffuse large B-cell lymphoma, leg type in a patient with chronic lymphedema of the leg. Indian J Pathol Microbiol [serial online] 2019 [cited 2019 Aug 19];62:470-2. Available from: http://www.ijpmonline.org/text.asp?2019/62/3/470/263490





   Introduction Top


Chronic lymphedema, a debilitating disease by itself, is associated with development of malignant tumors rarely. The most common being lymphangiosarcoma followed by lymphomas, Kaposi sarcoma, squamous cell carcinoma, and malignant melanoma. Association of cutaneous lymphomas with chronic lymphedema is unusual. We report an extremely rare occurrence of primary cutaneous large B cell lymphoma leg type in a patient with chronic lymphedema.


   Case Report Top


A 47-year-old woman who had bilateral lower limb lymphedema since childhood presented with worsening of the same since 3 years and development of multiple ulcers and nodules on both limbs from past 5 months. On general physical examination, patient looked pale. Local examination showed bilateral nonpitting edema of both the lower limbs extending up to the thigh region. Multiple ulcers with everted margins and multiple erythematous, painless nodules were present in both limbs. Nodules varied in size from 1 to 5 cm in diameter. They were firm in consistency. Nodules eventually broke to give rise to discharging ulcers with everted edges [Figure 1]. There was local inguinal lymphadenopathy with slight tenderness. Laboratory investigations revealed a raised total count of 12,500 cells/cmm with predominance of neutrophils, mild degree of anemia with Hb of 9.5 g/dL, and an elevated erythrocyte sedimentation rate (ESR) of 60 mm at the end of 1 hour. Liver enzymes and renal function tests were within normal limits. Biopsy from the ulcer and nodule was subjected to histopathological examination.
Figure 1: Nodule and an ulcer with everted edges on the leg

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Biopsies from the ulcer and nodule from both legs showed skin displaying atrophic epidermis. There was pandermal diffuse infiltration by atypical lymphoid cells having moderate amount of cytoplasm, hyperchromatic to vesicular nuclei, and prominent nucleoli [Figure 2]. The infiltrate was dissecting the collagen bundles. Areas of necrosis and apoptotic bodies were seen. Prominent focal angioinvasion and angiodestruction were seen [Figure 2]. Good numbers of mitotic figures were noted. Also seen was nuclear crush artifact and nuclear streaking. No epidermotropism was seen.
Figure 2: (a) Photomicrograph showing pandermal diffuse infiltration by atypical lymphoid cells (H and E, ×200). (b) Photomicrograph showing atypical lymphoid cells having moderate amount of cytoplasm, hyperchromatic to vesicular nuclei, and prominent nucleoli. (H and E, ×400). (c) Photomicrograph showing angioinvasion and angiodestruction by tumor cells (H and E, ×400)

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Immunohistochemical studies revealed tumor cells positive for CD10/20, BCL2, and BCL6 and negative for Tdt and CD3 [Figure 3]. MIB1 was variable and ranged from 20% to 70%. The morphology and immunohistochemical features were consistent with a diagnosis of primary cutaneous diffuse large B-cell lymphoma. Since the lesions were confined to the leg it was categorized as primary cutaneous diffuse large B cell lymphoma-leg type (PCLBCL LT). Unfortunately, patient succumbed to the disease within a week of diagnosis.
Figure 3: Photomicrograph showing immunohistochemical stains which revealed positivity for bcl6 (a) CD20 (b) bcl2 (d) and Ki67 (e) and negative for CD3 (c)

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   Discussion Top


A rare complication of chronic lymphedema is development of cutaneous malignant tumors most commonly lymphangiosarcoma followed by lymphomas, Kaposi sarcoma, squamous cell carcinoma, and malignant melanoma.[1] A literature review identified 12 additional cases of primary cutaneous lymphomas associated with chronic lymphedema.[2],[3],[4],[5],[6] These lymphomas presented in elderly individuals and in long-standing cases of chronic lymphedema of more than 10 years duration. Most of these cutaneous lymphomas were primary diffuse large B cell lymphoma and four of them were located in the leg including the present case which manifested with ulcero nodular lesions in the leg. In 2005, a new WHO – European organization for research and treatment of cancer was proposed. In this classification, primary cutaneous B-cell lymphomas were divided into the following three main groups: primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center cell lymphoma, and PCLBCL LT.[7] We report a new case of PCDLBCL LT associated with chronic lymphedema of leg.

PCLBCL LT constitutes 4% of all primary cutaneous lymphomas and typically occur in women with a M: F ratio of 1:3.[8] It is characterized by a predilection for the leg (72%) an advanced age at onset (mean age, 76 years), a high proportion of Bcl-2 expression (85%) and frequent relapses.[9] The overall 5-year survival is approximately 41%. Patients usually present with cutaneous nodules or tumors, deeply infiltrated plaques, large subcutaneous tumors, and leg ulcer. Location on the leg and multiple skin lesions was predictive of death in multivariate analysis.[9] The present case had lesions on the legs and died soon after the diagnosis. The nodular and ulcero nodular lesions on a chronic lymphedematous limb should raise a suspicion of malignancy and histopathological examination should be done as early as possible.

Histopathology shows large lymphoid cells of centroblastic and immunoblastic nature. Immunohistochemically, they are positive for CD20, bcl2, mum 1 protein, and negative for CD3 and tdt. In the present case, the cells were reactive for CD10/20, bcL2, and bcL6 and negative for Tdt and CD3. MIB1 was variable and ranged from 20% to 70%.

The association between chronic lymphedema and cutaneous primary lymphomas is not a coincidental condition. An inadequate lymphatic drainage due to chronic stasis of lymph may disrupt the regularity of lymphocytes and Langerhans cell trafficking, on which immunocompetence depends, making the lymphedematous region an immunologically vulnerable area, predisposing to infections and neoplasms.[6] Malignant lymphomas are the most common neoplasms seen in the context of immune dysregulation.[10]

PCLBCL LT is an aggressive lymphoma that requires effective therapies. This seems to be a difficult challenge in view of the advanced age of many patients.[9] Literature review has shown that 6 of the12 cases of primary cutaneous diffuse large B-cell lymphoma associated with chronic lymphedema ended up in recurrence of the lesion and three were fatal. And two of the three patients who died were those with lesions in the leg inferring that PLBCL LT has a poor prognosis.[6] Studies have shown that the prognosis of primary cutaneous diffuse large B cell lymphomas associated with chronic lymphedema does not significantly differ from that of primary cutaneous diffuse large B-cell lymphomas not associated with lymphedema.[9] However, PLBCL LT has an unfavorable prognosis.

Although angiosarcoma is the most frequent tumor arising in a lymphedematous limb, cutaneous lymphomas should be considered when dealing with cutaneous lesions in a chronic lymphedematous extremity since this differential diagnosis is important to prevent unnecessary surgery.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Ruocco V, Schwartz RA, Ruocco E. Lymphedema: An immunologically vulnerable site for development of neoplasms. J Am Acad Dermatol 2002;47:124-7.  Back to cited text no. 1
    
2.
Dargent JL, Lespagnard L, Feoli F, Debusscher L, Greuse M, Bron D. De novo CD5-positive diffuse large B-cell lymphoma of the skin arising in chronic limb lymphedema. Leuk Lymphoma 2005;46:775-80.  Back to cited text no. 2
    
3.
Tatnall FM, Mann BS. Non-Hodgkin's lymphoma of the skin associated with chronic limb lymphoedema. Br J Dermatol 1985;113:751-6.  Back to cited text no. 3
    
4.
Torres-Paoli D, Sanchez JL. Primary cutaneous B-celllymphoma of the leg in a chronic lymphedematous extremity. Am J Dermatopathol 2000;22:257-60.  Back to cited text no. 4
    
5.
Corazza M, Lombardi A, Strumia R, Cuneo A, Virgili A. Primary cutaneous plasmacytoma on chronic lymphoedema. Eur J Dermatol 2002;12:191-3.  Back to cited text no. 5
    
6.
González-Vela MC, González-López MA, Val-Bernal JF, Fernández-Llaca H. Cutaneous diffuse large B-cell lymphoma of the leg associated with chronic lymphedema. Int J Dermatol 2008;47:174-7.  Back to cited text no. 6
    
7.
Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al., WHO-EORTC classification for cutaneous lymphomas. Blood 2005;105:3768-85.  Back to cited text no. 7
    
8.
Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: Evolving concepts and practical applications. Blood 2011;117:5019-32.  Back to cited text no. 8
    
9.
Grange F, Beylot-Barry M, Courville P, Maubec E, Bagot M, Vergier B, et al. Primary cutaneous diffuse large B-cell lymphoma, leg type clinicopathologic features and prognostic analysis in 60 cases. Arch Dermatol 2007;143:1144-50.  Back to cited text no. 9
    
10.
Frizzera G, Rosai J, Dehner LP, Spector BD, Kersey JH. Lymphoreticular disorders in primary immunodeficiencies: New findings based on an up-to-date histologic classification of 35 cases. Cancer1980;46:692-9.  Back to cited text no. 10
    

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Correspondence Address:
Basavaraj Vijaya
Department of Pathology, JSS Medical College, Shivarathreeshwar Nagar, Mysuru - 570 015, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_581_18

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    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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