DR [Dermatology Reports 2011; 3:e51] [page 113] Cutaneous lesions as presentation form of mantle cell lymphoma Nayra Merino de Paz,1 Marina Rodríguez-Martín,1 Patricia Contreras Ferrer,1 Sonia García-Hernández,2 Nieves Hernández-León,2 Antonio Martín-Herrera,2 Antonio Noda-Cabrera1 1Dermatology and 2Pathology Department, Hospital Universitario de Canarias, University of La Laguna, La Laguna, Tenerife, Spain Abstract Mantle cell lymphoma is a type of non- Hodgkin lymphoma that affects extranodal areas, especially, bone narrow, digestive tract and Waldeyer ring. Here we report a case of mantle cell lymphoma IV Ann Arbor stage with cutaneous lesions on nasal dorsum and glans penis as the first manifestations. Skin involvement is a very rare manifestation and less than 20 cases have been reported in the literature. The importance of establishing multidisciplinary relationships for a global approach has been shown by this clinical case. Introduction Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma that frequently affects extranodal areas, especially, bone nar- row, digestive tract and Waldeyer ring. Other areas can also be affected too, however skin involvement is very rare.1,2 MCL is character- ized by specific morphologic, inmunopheno- typic and cytogenetic features [t(11;14)(q13;q32)] and cyclin D1 overex- pression.3 Case Report We report a 73-years-old man with a per- sonal history of bilateral cataracts, facial right paralysis, vertiginous syndrome treated with trimetazidin and teleangiectasic rosacea without treatment. He was referred to our Department from Otolaryngology (ORL) where he was assessed for presenting nasal obstruction three months ago. No fever, asthenia or anorexia were reported. Physical examination revealed: i) papular erythema- tous, infiltrated, 2.5 ¥ 2 cm of diameter lesion on nasal dorsum; ii) exulcerative, exudative lesion with an erythematous edge about 3¥4 cm of diameter in glans penis were observed (Figure 1). Blood test and cutaneous biopsies were performed. Histological examination of cutaneous lesions on face and penis showed diffuse lym- phocytic proliferation with middle size cells with irregular and clefted nucleous (Figure 2). Moderate mitotic activity was observed. Immunochemistry was positive for CD-20 and D1-Cyclin and negative for CD3 and CD10. Ki- 67 showed a high proliferation rate (Figure 3). These results were consistent with mantle cell lymphoma (MCL). Blood tests, including hemogram, biochemistry and hepatic profile were in normal ranges. ORL study included a turbinate biopsy. Diffuse lymphocytic tumoral proliferation infiltrates with middle size tumoral cells were observed. Tumoral cells showed clefted and irregular nucleous with granular chromatin, moderate mitotic rate and apoptotic bodies. Bone narrow biopsy, thorax Rx, CT scan, MRI, PET and cytogenetic study were performed. Limphocytic infiltrates showing features of MCL were observed in bone narrow. Multiple adenopathies and het- erogeneous high intensity sings in both lungs were observed in PET studies (Figure 4). Cytogenetic studies were performed and t(11;14) was observed by FISH. After hematologic and dermatologic assess- ment MCL IVA Ann Arbor stage and interme- diate-high IPI diagnosis was established. Four cycles of R-CHOP were administered every 21 days. A clear improvement after two cycles was observed (Figure 3). Two years later, the patient is still alive with Hematological, ORL and Dermatological peri- odical controls. Discussion The MCL represents around 10% of non- Hodgkin lymphomas (NHL). It usually affects medium or elder people. Skin involvement is rare, nevertheless, it can be the first manifes- tation of MCL. Only 19 cases of cutaneous MCL have been reported in the literature. It represents 2-6% of all NHL and the 17% are in stage IV. Men are more frequently affected than women (13:4) with a mean age of 63- years-old. Lesions usually appear in trunk, in contrast with our patient that presented the lesions first in face and genital area. A high variety in clinical appearence has been described. Nodular lesions are the most fre- quent clinical presentation, but macules, papules or plaques have been described too. Our patient presented two diferent clinical forms; nasal dorsum with papular presenta- tion and ulcerative clinical appearence in glans penis. Genital ulcerative form of cuta- neous MCL is uncommon. Up to 82% of patients with skin lesions present coexisting extracutaneous involvement, so extension studies are necessary to find other affected organs including blood tests, Rx, CT scan, MRI and PET. MCL has a median survival of 3- 5 years, with a better prognosis in patients with non-nodal disease. MCL is associated to a poor prognosis.3,4 The median survival time Dermatology Reports 2011; volume 3:e51 Correspondence: Nayra Merino de Paz, Servicio de Dermatología, Hospital Universitario de Canarias, Ofra s/n. La Laguna, Santa Cruz de Tenerife, 38320 Canary Islands, Spain. Tel. +34.22.678.492 - Fax: +34.22.319.293. E-mail: nayradepazhotmail.com Key words: cutaneous lymphoma, non-Hodgkin, mantle cell. Contributions: NMdP, NRM, AND, manuscript writ- ing; SGH, NHL, AMH, pathology studing; NMdP, PCF, SGH, NHL, AMH, data collecting and analyz- ing; MRM, PCF, ANC, manuscript reviewing. Conflict of interest disclosure: any author have a perceived or actual conflict of interest. Received for publication: 21 July 2011. Revision received: 7 October 2011. Accepted for publication: 9 November 2011. This work is licensed under a Creative Commons Attribution NonCommercial 3.0 License (CC BY- NC 3.0). ©Copyright N. Merino de Paz et al., 2011 Licensee PAGEPress, Italy Dermatology Reports 2011; 3:e51 doi:10.4081/dr.2011.e51 Figure 1. Clinical appearance of cutaneous lesions on face and glans penis. No n- co mm er cia l u se on ly [page 114] [Dermatology Reports 2011; 3:e51] is aproximately 3 years (range 2-5 years). The ten year survival rate is only 5-10%. Younger age and limited diseases are favorable prog- nostic features. Survival behavior of patients with cutaneous involvement is showed in Table 1. The skin involvement is considerer as independent prognostic factor, but it is uncertain.3,5,6 Treatment is difficult. First-line treatments for solitary lesions include surgi- cal excision, antibiotics, and radiotherapy. Systemic involvement needs an aggressive management. Only 30% of patients experi- enced a complete response. It is based in sin- gle akylating agents, CVP (cyclophosphamide, vincristine and prednisone) and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) regimens, Hyper-CVAD (hyperfractionated cyclophosphamide, dox- orubicin, vincristine, and dexamethasone) with or without rituximab, R-CHOP (CHOP plus rituximab) or Hyper-CVAD with autolo- gous stem cell transplantation. Our patient was treated with R-CHOP with a complete response. R-CHOP have showed a higher complete response rate than CHOP. Complications from chemotherapy may include infection, neutropenia, anemia, and thrombocytopenia, fatigue, neuropathy, dehy- dration after diarrhea or vomiting and cardiac toxicity from doxorubicin.6,7 Only ORL area involvement is also rare. So, our patient pre- sented with a very unique clinical picture. In fact, sinonasal lymphomas are relatively uncommon and represent less than 1% of all head and neck malignancies. T/NK cell lym- phoma is the most frequent in nasal cavity, however B-cell lymphoma is the main type in paranasal sinuses.8,9 So, here we present a rare case of MCL with cutaneous and nasal cavity lesions as presentation signs. The role of dermatologists is very important, in estab- lishing an early diagnosis. We have to consid- er this entity in the dermatologic differential diagnosis of tumours and we have to be aware about the importance of multidisciplinary approach. Case Report Figure 3. Clinical appearance after treat- ment. Table 1. Skin manifestation of mantle cell lymphoma. N Author Age/Gender Extracutaneous Stage Prognosis involvement 1 Ellison 66M Yes IV D (55 days after hospitalizazion) 2 Geerts 65F Yes IVA D (1.5 years after diagnosis) 3 Geerts 77F Yes IVA 4 Bertero 51M Yes IVA A (17 years after diagnosis) 5 Bertero 78F No IE D (3 years after diagnosis) 6 Bertero 43M Yes IVA A 7 Bertero 22M No IE A 8 Marti 61F Yes IVA D (15 months after diagnosis) 9 Moody 47M Yes IVA A (3 years after onset) 10 Dubus 56M Yes IVA D (1 year after treatment) 11 Dubus 89M Yes IVA D (5 days after diagnosis) 12 Dubus 72M Yes IVA A (1 year after treatment) 13 Sen 85M Yes IVB D (20 months after onset) 14 Sen 76M No IE A (30 months after onset) 15 Sen 56M Yes IVA A (21 months after onset) 16 Sen 57M Yes IVB D (19 months after onset) 17 Sen 61M Yes IVB D (17 months after onset) 18 Motegi 62M Yes A (4 months after diagnosis) 19 Estrozi 72M Yes IVA A (6 months after diagnosis) 20 Merino 73M Yes IVA A (2 years after diagnosis) Most of data adapted from Motegi S, Okada E, Nagai Y, Tamura A, Ishikawa O. Skin manifestation of mantle cell lymphoma. Eur J Dermatol. 2006 Jul-Aug; 16(4):435-8. D, dead; A, alive. Figure 2. Histological finding: a, b) Hema-toxylin and Eosin; c) CD20; d) CD3; e) CD10 and f ) D1-Cyclin stains. No n- co mm er cia l u se on ly [Dermatology Reports 2011; 3:e51] [page 115] References 1. Estrozi B, Sanches JA Jr, Varela PC, Bacchi CE. Primary cutaneous blastoid mantle cell lymphoma-case report. Am J Dermatopa- thol 2009;31:398-400. 2. Sen F, Medeiros LJ, Lu D, et al. Mantle cell lymphoma involving skin: cutaneous lesions may be the first manifestation of disease and tumors often have blastoid cytologic features. Am J Surg Pathol 2002 26:1312-8. 3. Motegi S, Okada E, Nagai Y, e al. Skin manifestation of mantle cell lymphoma. Eur J Dermatol 2006;16:435-8. 4. Lai R, Medeiros LJ. Pathologic diagnosis of mantle cell lymphoma. Clin Lymphoma 2000;1:197-208. 5. Bosch F, Lopez-Guillermo A, Campo E, et al. Mantle cell lymphoma: presenting fea- tures, response to therapy, and prognostic factors. Cancer 1998;1:567-75. 6. Swerdlow SH, Kurrer M, Bernengo M, Buchner S. Cutaneous involvement in pri- mary extracutaneous B-cell lymphoma. In: Weedon D, LeBoit P, Burg G, Sarasin A, eds. Pathology and Genetics of Tumors of the Skin: WHO Classification of Tumors. Lyon: IARC, 2005. pp 204-6. 7. Weigert O, Unterhalt M, Hiddemann W, Dreyling M. Mantle cell lymphoma: state- of-the-art management and future per- spective. Leuk Lymphoma 2009;50:1937- 50. 8. Van Prooyen Keyzer S, Eloy P, Delos M, et al. Sinonasal lymphomas. Case report. Acta Otorhinolaryngol Belg 2000;54:45-51. 9. Vidal RW, Devaney K, Ferlito A, et al. Sinonasal malignant lymphomas: a dis- tinct clinicopathological category.Ann Otol Rhinol Laryngol 1999;108:411-9. Case Report Figure 4. Upper side: Preauricular, retroauricular, occipital, submandibular, subcarinal, right hilum and groin lymphadenopathies, heterogeneuos. Lower side: High intesity sings in both lungs were observed in PET studies. No n- co mm er cia l u se on ly