A case of primary cutaneous B cell lymphoma of the knee1. Epsom General Hospital, Dorking Road, Surrey, United Kingdom. firstname.lastname@example.org
EJH Turner PhD1, N Tsim MRCS2, J Pawade FRCPath2, L Wolowczyk FRCS2
Dermatology Online Journal 15 (7): 6
2. Bristol Royal Infirmary Upper Maudlin Street, Bristol, United Kingdom
We report the case of a gentleman with a primary cutaneous B cell lymphoma of the leg who underwent an amputation and later died. This is an uncommon type of cutaneous lymphoma with poor prognosis and the case demonstrates how aggressive the tumor can become.
We report a case of a 97-year-old gentleman with a high grade primary cutaneous diffuse large B cell lymphoma of leg type involving the left knee. He was transferred to our vascular unit after the oncologists had assessed him and decided his ulceration was unsuitable for radiotherapy. Past medical history included a total knee replacement on the affected side 21 years ago, rate controlled atrial fibrillation, hypertension, transient ischemic attacks, and cataracts.
|Figure 1||Figure 2|
|Figure 1. Large area of ulceration of the knee prior to amputation
Figure 2. Magnification 400, sheets of lymphoid blasts with hyperchromatic nuclei
On examination the patient had a large 16 x 13 cm ulcer down to bone (Fig. 1), with associated soft tissue necrosis and superimposed infection. Ulcer edges were edematous. The patient was not systemically septic, had reasonable urine output and was not confused. However, he was frail and appeared poorly nourished. Preoperative basic blood investigations were normal. Intravenous fluids and broad spectrum antibiotics were commenced. It was decided that an amputation was required in order to prevent sepsis and gangrene and also to provide cure for the lymphoma.
|Figure 3||Figure 4|
|Figure 3. Strong membrane expression of CD20 on tumor cells
Figure 4. High proportion of tumor nuclei show immunoreactivity for Ki67
After informed consent (including that for the use of photography and publication of images) the patient was taken to the operating room. Spinal anesthesia and sedation was used. An above knee amputation was performed using equal anterior and posterior skin flaps and was taken higher than usual to be clear of the metal knee prosthesis and to allow adequate excision margin away from the lymphoma. Tissues were found to be markedly edematous intraoperatively. Postoperatively, he initially did well and there was minimal drainage from the wound and drains were therefore removed after 24 hours. Postoperative hemoglobin was 12.7 (down from 13.2).
An histology specimen included 17 cm of distal femur and confirmed an extensive malignant lymphoma (high grade diffuse large cell B cell lymphoma) underlying the large ulcer, the tumor site showing extensive necrosis. The tumor involved the soft tissue surrounding the knee diffusely, but also infiltrated the capsular and synovial tissue. The tumour showed strong expression of CD20 and BCL2 and strong nuclear expression of MUM1 and BCL6. No staining was seen for CD138. Ki67 identified 95 percent of tumor nuclei. It confirmed the proximal margin to be free of tumor and presence of a prosthesis.
Postoperatively on day 3 the patient developed a lower respiratory tract infection and he was treated with intravenous antibiotics and fluids and chest physiotherapy. He went on to develop fast atrial fibrillation and left ventricular failure and urine output tailed off. He was treated with strict fluid balance and started on digoxin. On day 4 postoperatively the patient decided he'd had enough of medical intervention and decided not to have further IV antibiotics or fluids and was treated with oral antibiotics and fluids. The palliative team were involved to help keep him comfortable and he was started on amitryptilline because he was complaining of phantom pain. He was transferred to a hospice on day 9 where he later died.
Primary cutaneous diffuse large B cell lymphoma is an uncommon type of cutaneous lymphoma making up 20 to 25 percent of all cutaneous lymphomas and has poor prognosis [1, 2]. It is an extranodal type of B cell lymphoma that is confined to the skin and has no extracutaneous involvement at the time of diagnosis . It has a tendency to occur in elderly patients, is more common in women, and is usually confined to the lower legs .
Primary cutaneous large B cell lymhomas (PCLBCLs) may be categorized using a combination of the World Health Organization/European Organization for Research and Treatment of Cancer (WHO/EORTC) classification and the newer TNM staging scheme of the International Society of Cutaneous lymphomas (ISCL/EORTC TNM classification system) [1, 4]. Primary cutaneous large B cell lymhomas are divided into 3 groups: primary cutaneous marginal zone B cell lymphoma (pcMZL), follicle center lymphoma (pcFCL), and diffuse large B cell lymphoma, leg-type (pcDLBL), and the TNM system categorises them as solitary (T1), regionally clustered (T2) and disseminated (T3) [1, 4]. Primary cutaneous T-cell lymphoma has also been described in the lower leg as a locally aggressive variantwith distinctive clinical and pathological features .
This case was the diffuse large B cell lymphoma, leg-type (pcDLBL). The morphology with mononuclear immunoblasts and phenotype of BCL-2 positivity with MUM-1 expression with high Ki67 is characteristic of this lymphoma, with an activated profile. Overall 5-year disease-specific survival tends to be 41 percent and location on the leg and multiple lesions in the skin have been shown to be predictive of death . Radiotherapy is considered the first line therapy but different treatment modalities have been used to treat it with varying success including chemotherapy, radiotherapy and immunotherapy [2, 6, 7, 8]. It is often resistant to chemotherapy but improvement in the prognosis has been found following treatment using combination of anthracycline-containing chemotherapies and rituximab, a chimeric monoclonal IgG1 antibody directed against the CD20 antigen of B cells which is generally fairly well tolerated [7, 8].
This case highlights how aggressive and infiltrative these lymphomas can become, needing amputation. This lymphoma in the elderly should be included in the differential diagnosis of an ulcer.
References1. Senff NJ, Noordijik EM, Kim YH et al. European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas. Blood 2008. 112(5): 1600-9. [PubMed]
2. Zinzani PL, Quaglino P, Pimpenelli N, Berti E, Swedlow SH, Baliva G, Rupoli S et al Prognostic Factors in Primary Cutaneous B. Cell Lymphoma: the Italian study group for cutaneous lymphomas. J Clin Oncol 2006, 20: 1376-82. [PubMed]
3. Willemze R, Jaffe E, Burg G, et al: WHO-EORTC classification of cutaneous lymphomas. Blood 2005, 105 : 3768 -3785. [PubMed]
4. Golling P, Cozzio A, Dummer R, et al. Primary cutaneous B-cell lymphomas-clinicopathological, prognostic and therapeutic characterization of 54 cases according to the WHO-EORTC classification and the ISCL/EORTC TNM classification system for primary cutaneous lumphomas other than mycosis fungoides and Sezary syndrome. Leuk Lymphoma 2008; 49(6): 1094-103. [PubMed]
5. Poligone B, Wilson LD, Subtil A et al. Primary cutaneous T-cell lymphoma localized to the lower leg: a distinct, locally aggressive cutaneous T-cell lymphoma. Arch Dermatol. 2009; 145(6): 677-82. [PubMed]
6. Moore MM, Kovich OI, Brown LH. Primary cutaneous B-cell lymphoma (low grade, non large cell).Dermatol Online J. 2007, 13:8. [PubMed]
7. Grange F, Maubec E, Bagot M, et al. Treatment of cutaneous B cell lymphoma, leg type with age-adapted combinations of chemotherapies and rituximab. Arch Dermatol 2009; 145(3): 329-30. [PubMed]
8. Garcia CP, Florez A, Pardavilla R, et al. Primary cutaneous large B-cell lymphoma, leg type, successfully treated with rituximab plus chemotherapy. Eur J Dermatol 2009; 19(4): 394-395. [PubMed]
© 2009 Dermatology Online Journal