Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma that most commonly affects men above the age of 60 years. The disease is called MCL because the tumor cells originate from the mantle zone of the lymph node. The most commonly affected sites are the lymph nodes, bone marrow, gastrointestinal tract, Waldeyer’s ring and rarely the skin, breast and central nervous system. Only 22 cases with skin manifestation of MCL have been reported so far.
We report the case of a 73-year-old woman who was diagnosed with MCL and underwent treatment, but later relapsed and presented with an ulcerated mass over her right foot. She underwent 6 cycles of chemotherapy with bendamustine plus rituximab and responded with resolution of the foot lesion.
MCL is an aggressive lymphoma with a median overall survival of 3-5 years for advanced disease, while early-stage disease has a better prognosis. It rarely involves the skin. Since cutaneous lesions can be the first manifestation of MCL, awareness of this less common presentation is crucial to establish an early diagnosis and pursue treatment as early as possible, as it significantly impacts the survival rate.
Tumori 2016; 102(Suppl. 2): e137 - e140
Article Type: CASE REPORT
AuthorsArash Samarghandi, Shradha Ahuja, Sorab Gupta, Ilmana Fulger, Gordana Katava, Yanan Fang
- • Accepted on 20/09/2015
- • Available online on 29/10/2015
- • Published online on 11/11/2016
This article is available as full text PDF.
Mantle cell lymphoma (MCL) is a rare type of lymphoma comprising about 6% of all non-Hodgkin lymphoma. It has a characteristic chromosomal translocation, t(11;14), between the immunoglobulin heavy chain on ch14q32 and the CCND1 gene on ch11q13, and regularly overexpresses the bcl-1 protein, also known as cyclin D1. The median age at diagnosis is 60 to 65 years. A male predominance of approximately 3:1 is observed. It is generally not a curable disease and has a moderately aggressive clinical course, classifying it as an intermediate-grade lymphoma (1-2-3). About 70% of MCLs are diagnosed at stage III/IV with extensive lymphadenopathy and bone marrow involvement (4). Eighty percent of patients with MCL have splenomegaly (2). Other extranodal manifestations include gastrointestinal tract lesions, eye involvement, and rarely skin, lacrimal gland and central nervous system involvement (5). We describe an unusual extranodal involvement in a patient who was diagnosed with MCL 2 years before presenting with an ulcerated mass on the right foot that was subsequently found to be secondary to disease relapse.
A 73-year-old woman presented to the emergency room with a painful right foot mass. She reported a foot injury 5 months earlier but only recently noticed the mass to be progressively increasing in size. She had been diagnosed with MCL in 2012 and had received immune-chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). She remained in remission since then but was subsequently lost to follow-up.
Physical exam was significant for bilateral inguinal and axillary lymphadenopathy and a palpable, raised, nonfluctuant, indurated, nonmovable soft tissue mass measuring 6 × 6 cm over the dorsolateral aspect of the right foot. The soft tissue mass had a central area of necrosis measuring 0.5 × 0.5 cm with surrounding erythema and edema encompassing the length of the fifth metatarsal bone with minimal drainage and tenderness (
Foot mass. Lesion on the right foot secondary to MCL (
She was started on broad-spectrum antibiotics for possible infectious etiology. PET/CT showed large bulky common iliac nodal masses and external and internal iliac nodal masses. The inguinal nodal masses were predominantly right-sided with significant hypermetabolic activity (
PET scan. PET images showing inguinal and iliac lymphadenopathy.
Histological sections of the soft tissue mass from the foot (
Tissue slide from foot specimen showing prominent lymphoid infiltrate.
The patient was started on bendamustine and rituximab, of which she received 6 cycles. Interim examination of the foot after each cycle revealed a continued decrease in size of the mass and eventual complete resolution (
MCL is a B-cell lymphoma which originates from pre-germinal naive B cells from the mantle zone of the lymphoid follicles. According to the WHO classification, the diagnosis of MCL should be based on clinical, histopathological, immunological and cytogenetic or molecular data. Histologically, the lymph nodes exhibit effacement by a monomorphic lymphoid proliferation, typically composed of small to medium-sized lymphocytes with irregular or cleaved nuclei, most closely resembling centrocytes. Immunophenotypically, the tumor cells are positive for the markers CD5, SOX11, FMC7 and B-cell markers (CD19, CD20, CD22, CD79a) (1, 6).
MCL is an aggressive lymphoma with a median overall survival of 3-5 years for patients with advanced MCL. Current therapeutic strategies have not resulted in cure. Relapses are common in the course of the disease (1). Most relapses occur within 12-24 months after detection of the primary disease.
MCL frequently involves extranodal organs including the bone marrow, gastrointestinal tract and Waldeyer’s ring but rarely affects the skin (6). In a large series of 121 cases of MCL only 3 had skin lesions., respectively (5). The most common sites of skin involvement in MCL are the trunk (60%), face (30%), arm (20%), thigh, leg, and scalp (6, 7). Skin lesions manifest as nodular lesions (34%), macular or maculopapular lesions (34%), tumoral or infiltrated plaques (21%), and subcutaneous nodules (11%) (6, 7). To our knowledge there have been no case reports presenting MCL relapse in the foot.
The most recommended treatment for MCL relapse in chemosensitive cases is bendamustine and rituximab (BR regimen) as salvage regimen. In some clinical trials, the overall response rate to the BR regimen was as high as 90%, with 60% complete response and median progression-free survival of 30 months (8). However, agents targeting a known signaling pathway have been tested for treating relapse of refractory MCL, including the proteasome inhibitor bortezomib, the mTor inhibitor temsirolimus, and lenalidomide; these agents showed promising responses against relapsed or refractory MCL (9).
Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib is a highly active new agent showing durable single-agent activity in relapsed and refractory mantle-cell lymphoma (10). The US FDA has approved ibrutinib for the treatment of MCL in patients who have received at least 1 prior therapy. In a phase II clinical trial of ibrutinib, patients with relapsed or refractory MCL who had received a median of 3 prior therapies had an overall response rate of 68% (21% complete), with an estimated median duration of response of 17.5 months (11).
High-dose chemotherapy with autologous stem cell transplant is not considered as a first-line therapy in relapsed cases; however, there are clinical trials showing promising results with a 5-year overall survival of 44% (12). The prognosis of MCL with skin localizations is poor, although aggressive chemotherapy may improve the survival rate (6). Among the 18 cases of MCL with cutaneous manifestation reported, most patients received aggressive combination chemo-therapy and 14 patients died 5 days to 3 years after diagnosis. Since cutaneous lesions can be the first manifestation of MCL, awareness of this less common presentation is crucial to establish an early diagnosis and pursue treatment as early as possible (6).
We thank the patient for allowing us to share her details.
- Samarghandi, Arash [PubMed] [Google Scholar] 1
- Ahuja, Shradha [PubMed] [Google Scholar] 1
- Gupta, Sorab [PubMed] [Google Scholar] 1, * Corresponding Author (firstname.lastname@example.org)
- Fulger, Ilmana [PubMed] [Google Scholar] 2
- Katava, Gordana [PubMed] [Google Scholar] 3
- Fang, Yanan [PubMed] [Google Scholar] 4
Department of Internal Medicine, Saint Barnabas Hospital, Bronx, New York - USA
Department of Hematology-Oncology, Saint Barnabas Hospital, Bronx, New York - USA
Department of Hematology-Oncology, Montefiore Medical Center, Bronx, New York - USA
Wakefield Clinical Laboratories, Department of Pathology, Montefiore Medical Center, Bronx, New York - USA