Figure 3, Right foot after the 5th cycle of BR treatment. Unusual Presentation of Mantle Cell in the Foot Arash Samarghandi MD, Rihamary Jimenez DPM, Ilmana Fulger MD St. Barnabas Hospital, Bronx, NY

Introduction Case Report Continued Discussion

Mantle cell lymphoma (MCL) is a rare type of lymphoma, it MCL is a B-cell lymphoma which originates from pregerminal naive B cells comprises about 6% of all non Hodgkin’s lymphoma. It is generally Bone biopsy showed a normocellular with trilineage from the mantle zone of the lymphoid follicles. It is first suggested by not curable, with a moderate aggressive clinical course, and is hematopoiesis with mild myeloid hyperplasia with myeloid to erythroid Rapport in 1960s 6 , and later completely described by Berard and classified as an intermediate –grade lymphoma. 1,2,3 ratio 4-6 to 1. Several diminished interstitial lymphoid aggregates were Dorfman in 1974. 7 About seventy percent of MCLs are diagnosed in stage III/IV with noted. (Figure 4) Over time different names were used to describe MCLs such as

4 Immunophenotyping by flow cytometry showed predominant CD 20+ centrocytic lymphoma, intermediate lymphocytic lymphoma, extensive lymphadenopathy and bone marrow involvement , eighty percent with splenomegaly 2 . Other extranodal B-cells, also positive for CD5. Sparse were positive for lymphocytic lymphoma of intermediate differentiation and mantle zone manifestations include gastrointestinal tract , eye involvement and Cyclin D-1, suggestive of mantle cell lymphoma. lymphoma. However according to Revised European- American rarely skin, lacrimal glands and CNS involvement. 5 Patient was started on a Bendamustine and Rituxan regimen for Classification of lymphoid neoplasm, MCL is recognized as a distinct We describe an unusual extranodal involvement in a patient who intended 6 cycles with PET/CT scan to be repeated after 4 cycles. She entity. was diagnosed with MCL two years ago and now presents with a may subsequently need autologous SCT. To date, patient has completed MCL is an aggressive lymphoma with poor prognosis, with median right foot ulcer, consistent with MCL relapse. 5 cycles of BR treatment,with clear improvement to right foot (Figure3). survival of 3- 5 years. Relapses are common 1,8,9 . Current therapeutic strategies have not resulted in cure. The most recommended treatment for relapse of MCL in chemo-sensitive Case Report Images cases is Bendamustine and Rituximab (BR regimen). In some clinical trials, overall response rate of BR regimen shown to be 90% with complete response of 60% and median Progression free survival of 30 73 year old female with past medical history of Diabetes Mellitus, months. 13 However agents targeting a known signaling pathway have hypertension and hyperlipidemia presented to the emergency room been tested in treating relapse of refractory MCL, such as Bortezomib with the chief complaint of a painful right foot ulcer with erythema. (proteasome inhibitor), Temsirolimus ( mTor inhibitor) or lenalidomide The patient was diagnosed two years ago (2012) with MCL treated with with promising responses against relapse/refractory MCL. 14,15 chemotherapy and was in remission : R-CHOP (rituximab, High dose chemotherapy with autologous stem cell transplant (ASCT) is cyclophosphamide, doxorubicin, vincristine, and prednisone). Patient not considered a first line therapy in relapse cases, however there are had failed to follow up with hematology/oncology for 1 year. clinical trials showing promising results with ASCT with a five year overall During this visit, patient stated that she initially injured her foot on a survival of 44%. 16 9 rocking chair about five months ago. Patient stated that her right foot Most of the relapses occur within 12-24 months after primary disease. had gotten increasingly more swollen and recently noted discharge MCL arising from soft tissue is rare, accounting from 0.11% to 2% of from an ulcerated area. primary . There are case reports where MCL occurs in the 10,11,12 On physical exam, the patient was afebrile with no constitutional calf, ankle, shoulder and chest wall. To our knowledge there have been no case reports presenting MCL symptoms. Enlarged right inguinal lymph nodes were noted measuring Figure 1. Lesion on the right foot Figure 2. Lesion after the 1st cycle approximately 5 cm. A palpable, raised, indurated, non-movable soft secondary to MCL. of BR treatment. relapse in foot. tissue mass measuring 6x 6cm with centralized area of necrotic eschar measuring 0.5 x 0.5 cm noted on the dorsolateral aspect of right foot References with erythema and edema encompassing the length of the fifth

metatarsal bone. Minimal drainage and tenderness was noted upon 1. Jonathan H. Hughes, N. P. (1998). Blastic variant of mantle-cell lymphoma: cytomorphologic, immunocytochemical, and molecular genetic features of tissue obtained by fine-needle aspiration biopsy. diagnostic cytopathology , 19 (1), 59-62. palpation. No fluctuance was noted (Figure 1). 2. Vose, J. M. (2013). mantle cell lymphoma: 2013 update on diagnosis,risk-stratification, and clinical management. american journal of hematology , 88 (12), 1082-1088. On X-ray examination, there was extensive soft tissue prominent lateral 3. Rosenwald, A. (2003). The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival and dorsal to the fifth metatarsal, suspicious for cellulitis. No focal in mantle cell lymphoma. cencer cell , 3 (2), 185-97. 4. Micah, p. (2014, july). Mantle Cell Lymphoma Metastasis to the Gallbladder. the american surgeon , 198-199. rarefaction or periosteal reaction to suggest osteomyelitis was 5. Samaha, H. d. (1998). Mantle cell lymphoma: a retrospective study of 121 cases. , 12 (8), 1281-1287. 6. Harris, N. J. (1999). the world health organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. report identified. of the clinical advisory comittee meeting, airlie house, virginia, November,1997. ann oncol , 10 (12), 1419-32. 7. Berard CW, D. R. (1974). Histopathology of malignant lymphomas. clin haematol , 3, 39-45. An ultrasound was performed on the palpable lesion of the right foot 8. Richard I. FIsher, S. H. (2006). multicenter phase II study of bortezomib in patients with replased or refractory Mantle cell lymphoma. American society of clinical Oncology , 24 (30), 4867-74. which showed complex, inhomogeneous mass in the area which is 9. M.Dreyling, C. G.-N. (2014). Newly diagnosed and relapsed mantle cell lymphoma. Annuals of oncology , 25, 83-92. 10. Skarin, A. (2001). Dignosis In Oncology. Journal of Clinical Oncology , 19, 3288-3293. palpable with indistinct margins. The patient was started on renal dose 11. Travis WD, B. P. (1987). Primay Extranodal Soft tiuss lymphoma of the extremities . Am J Surg Patho , 11, 359-366. of Vancomycin and Zosyn for possible infectious etiology. 12. Anna R. Thorner, A. C. (2001). Unusual Presentations of Malignancy . American Society of Clinical Oncology , 19 (13), 3291-3293. th 13. Rummel M, A. J. (2005). Bendamustine and Rituximab are effective and has a favorable toxicity profile in the treatment of Mantle cell Hematology/ Oncology was consulted and prompted for bone biopsy to Figure 3. After 5 cycle of BR Figure 4. Lymphoid hyperplasia of and low grad non-hodgkin's lymphoma. J Clin Onc , 23, 3383-3389. treatment bone marrow. 14. Friedberg JW, V. J. (2009). Bortezomib in patients with relpased or refractory mantle cell lymphoma. Ann Onc , 117, 520-525. 15. Witzig TE, R. C. (2011). A phase II tiral of the oral mTOR inhibitor everoliumus in relapsed aggressive lymphoma. Lukemia , 25, 341-347. rule out sarcoma vs acral amelanotic melanoma. PET/CT scan on this 16. Fenske TS, C. J. (2011). Out come of patients with mantle cell lymphoma undergoing autologous versus reduced-intensity allogeneic admission revealed multiple lymphadenopathies. transplantation. Ann Onc , 22. IRB Number 2015.24 May 2015