Primary Cutaneous Follicle Center Lymphoma

Vol. 20, No. 2, June 2009 – Hejab SA et al.

Received: 12 September 2008 Accepted: 1st referee: 10 October 2008 2nd referee: 15 November 2008

Primary Cutaneous Follicle Center Lymphoma Diffuse Large B cell Variant Hejab S Al-Ajmi*, Aida M Abdulkader** and Abdel Monaem M Mustafa*** Department of Dermatology*, Al-Amiri Hospital, Ministry of Health, Kuwait, Dermatology & Venereology**, Alexandria University, Egypt & Al-Amiri Hospital, Kuwait and Dermatology & Venereology***, Al-Azhar University & Al-Amiri Hospital, Kuwait

mary cutaneous B-cell lymphomas (PCBCLs) are peripheral B-cell neoplasms that present in the skin and presumably originate from a B-cell compartment with special preference for the skin microenvironment(2,3).

Abstract Cutaneous follicular lymphoma is the most common type of primary B-cell lymphoma of the skin. Based on architectural features, it could be classified as follicular, follicular &diffuse and minimally follicular. Rarely, exclusively diffuse follicular pattern may be seen (!). Our case was a 40-year-old male had grouped, glistening, firm, reddish nodules on the scalp of about a year. No lymph node affection was detected either clinically or by CT scanning. Lesional Skin biopsy revealed diffuse dense atypical large B-cell lymphocytic infiltrate occupying the whole dermis with marked nuclear pleomorphism. In addition, diffusely coalescent follicles were noticed. The specimen was moderately positive for bcl-2 stain. The clinicopathologic features were those of primary cutaneous B cell lymphoma. The patient prescribed herein had a unique presentation of diffuse large B lymphoma as a variant of primary cutaneous follicle center lymphoma.

Our patient was a 40-year-old male presented with asymptomatic skin lesions on the scalp of about a year. The lesions consisted of grouped, glistening, firm, reddish nodules (Figs. 1A & B). Alopecia was present in the involved area. The tumors were surrounded by erythema (Fig. 2). There were no clinically palpable regional lymph nodes. Clinical differential diagnosis at that time was cutaneous pseudolymphoma, lymphoma and skin metastsis. Chemistry profile, complete blood count, serum immune-electrophoresis & urine analysis were all normal. Radiological evaluation revealed no abnormal findings regarding X-rays of skull, chest, lumbosacral spines & pelvis as well as ultrasongraphy (abdomen, pelvis). CT scan suggested no evidence of lymphadenopathy or involvement by lymphoma. Gallium scan showed avid soft tissue uptake in left side of scalp. Bone marrow was normocellular & uninvolved. Lesional Skin biopsy was taken and subjected to routine histopathology using H & E stain and immunohistologic study. H & E

Case report Primary cutaneous lymphomas are thought to be approximately 65% T cell in origin, whereas only 20–25% are thought to originate from B cells. Pri49


stained specimen showed diffuse dense mononuclear infiltrate involving the entire dermis even the papillary portion (Figs. 3A & B). Atypical large cells with marked nuclear pleomorphism & prominent mitoses were seen (Fig. 4). Uniform sized coalescent follicles were noticed (Fig. 5). Peri-adnexal & Perivascular infiltration was evident (Figs. 6, 7).The infiltrate was intersecting the dermal collagen bundles (Fig. 8).

showed moderately positive staining for bcl-2 (Fig.10). Clinical, H & E histopathology, immunophenotyping, immunohistochemistry, radiologic & CT scan findings confirmed the diagnosis of primary Cutaneous follicle centre B cell lymphoma - diffuse large B cell pattern. Our patient believed in non-medicated herbal applications, but the tumors increased in size with telangiectatic surface (Fig. 11). Serology for both B. burgdorferi and H. pylori was negative. The patient received six cycles of radio-chemotherapy (R-CHOP) in KCCC (Kuwait cancer centre control) with apparent clinical clearance of the tumors leaving residual scarring (Fig. 12).

Immunophenotyping illustrated that the infiltrate was mostly CD20 positive denoting B cell lymphocyte in origin (Figs. 9A & B); focal patches of reactive T lymphocytes with positive immunostain for CD3. The infiltrate was negative for CD10, CD15 and CD30 immunostains. The specimen

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thologically simulated DLBCL. In our patient, the infiltrate was diffuse, predominantly of atypical large cells with marked nuclear pleomorphism & prominent mitoses. This confirms Hoefnagel J.J. et al.(8) view that most primary cutaneous follicle centre cell lymphomas (PCFCCLs) display a diffuse pattern, whereas a follicular growth pattern is observed in only a minority of cases(8).

Discussion Primary cutaneous B-cell lymphomas are a heterogeneous group of extranodal lymphomas characterized by distinct clinical and histopathological features. Issues of PCBCLs classification are still controversial. For example, in the Dutch and European Organization for Research and Treatment of Cancer (EORTC) classifications, distinction is made between three main subtypes, follicle centre cell (FCC) lymphoma, immunocytoma (IC) / marginal zone lymphoma, and diffuse large B-cell lymphoma (DLBCL) of the leg(4,5). The corresponding categories according to the WHO classification are follicular lymphoma, extranodal marginal zone lymphoma of MALT type and diffuse large B-cell lymphoma. So, cases of CLBCL-leg are considered as diffuse large B-cell lymphoma in the WHO classification(6,7). Others have argued that PCBCLs can be classified using the Revised European–American Classification of Lymphoid Neoplasms (REAL) approach; that FCC lymphomas are rare in the skin whereas marginal zone lymphomas are frequent; that marginal zone lymphomas are not equivalent with IC, but constitute a separate disease; and that PCBCL predominated by large cells should be designated as such, i.e. as DLBCL(2). Thus, our case is unique as it had the typical localization (scalp) and indolent clinical behavior like FCC while histopa-

According to the recent new WHO–EORTC classification, five types of PCBCLs can be distinguished: follicle centre lymphoma (FCL), marginal zone lymphoma (MZL) / immunocytoma, diffuse large B-cell lymphoma – leg type (PCLBCL-L), diffuse large B-cell lymphoma-other (This group refers to cases of large B-cell lymphoma arising in the skin which do not belong to the groups of PCFCL and PCLBCL, leg type) and intravascular large B-cell lymphoma. In this new classification: the previous EORTC term of primary cutaneous follicular centre cell lymphoma has been replaced by the 2001 WHO term of primary cutaneous follicular centre lymphoma, reflecting that the tumour can have follicular, follicular and diffuse or purely diffuse growth patterns(9,10). So, we can categorize our case as primary cutaneous follicular centre lymphoma, diffuse large B-cell variant. Studies the defects in genes and gene products involved in apoptosis and cell cycling are likely to

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be of major importance. These include the bcl-2 family. It is well established that a majority of nodal FCC lymphomas carries at (14; 18) translocation, resulting in over expression of bcl-2 relative to normal FCC cells. Conflicting results have been obtained in studies of bcl-2 expression in PCBCL. Cerroni et al.(11) have suggested that there are differences between FCC lymphomas (bcl-2-negative) and MALT-type lesions (bcl-2-postive), and Geelen et al.(12) have suggested that expression of bcl-2 is site related, i.e. positive in DLBCL of the legs and negative in PCBCL at other sites. However, a recent study has investigated chromosomal aberrations in PCLBCL, leg type and PCLBCL, other and has found similar aberrations irrespective of anatomical site, cell morphology and bcl-2 expression(13). Moreover, Several studies described the presence of a follicular growth pattern as well as the expression of bcl-2, the germinal centreassociated antigens bcl-6 and CD10, and at (14;18) in variable proportions of primary cutaneous follicle centre cell lymphomas (PCFCCLs), suggesting that the neoplastic B cells in these PCFCCLs are indeed of follicle centre cell origin and that they are closely related to nodal follicular lymphoma. It has been suggested that expression of bcl-2 protein by 50% of tumour cells should be employed as a cutoff for bcl-2 positivity in B-cell lymphomas(14,15). In our report, the infiltrate showed moderately positive staining for bcl-2. Therefore, more comprehensive investigations are needed before potential differences in bcl-2 expression by different subtypes of PCBCL can be delineated.

We present a case of PCBCL that had combined clinicopathologic features of both primary cutaneous FCL (PCFCL) and DLBCL. Thus, our case represents primary cutaneous diffuse large B cell lymphoma variant of PCFCL. This agrees with the recent concept of WHO–EORTC classification that cases of primary cutaneous diffuse large B-cell lymphoma are divided into three groups: large Bcell lymphoma -leg type (LBCL-L), LBCLs as a variant of primary cutaneous follicle center lymphoma {our case}, and a third group including all LBCLs that do not fulfill the criteria of the first two groups(19).

References

Apart from radiotherapy, therapeutic options for PCBCL include various modalities depending on the histological subtype and the number of lesions: surgical excision, interferon-α, chemotherapy and, more recently, monoclonal antibodies (rituximab). PCBCLs are generally characterized by an indolent course (5-year survival > 95%), rare dissemination to internal organs, but a high incidence of recurrence (25–68% of patients)(16,17,18). As our patient expressed bcl-2, he received radio-chemotherapy (6 cycles of R-CHOP) with excellent response and follow-up for three years revealed no recurrence.

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‫اﻝورم اﻝﻠﻨﻔﺎوى اﻝﺠﻠدي اﻷوﻝﻲ ﻝﻤرﻜز اﻝﺠرﻴب اﻝﻨوع اﻝﻤﺴﻬب ﻝﻠﺨﻠﻴﺔ اﻝﺒﺎﺌﻴﺔ اﻝﻜﺒﻴرة‬ ‫ اﻋﺘﻤﺎدا ﻋﻠﻰ اﻝﺼور اﻝﻬﻴﻜﻠﻴﺔ ﻴﻤﻜن ﺘﻘﺴﻴم ﻫذﻩ‬. ‫ﻴﻌﺘﺒر اﻝورم اﻝﻠﻨﻔﺎوى اﻝﺠرﻴﺒﻲ اﻝﺠﻠدي ﻫو أﻜﺜر اﻷورام اﻝﻠﻨﻔﺎوﻴﻪ اﻝﺠﻠدﻴﺔ اﻷوﻝﻴﻪ ﺸﻴوﻋﺎ ﻝﻠﺨﻼﻴﺎ اﻝﺒﺎﺌﻴﺔ‬ ‫ وﻤرﻴﻀﻨﺎ ﻋﻤرﻩ أرﺒﻌﻴن ﻋﺎﻤﺎ و ﻴﻌﺎﻨﻲ‬.‫ ﻨﺎد ار ﻤﺎ ﻴرى ﻫذا اﻝورم ﺤﺼ ار ﺒﺸﻜل ﺠرﻴﺒﻲ ﻤﺴﻬب‬.‫اﻷورام إﻝﻰ ﺠرﻴﺒﻴﻪ و ﺠرﻴﺒﻴﻪ ﻤﻊ ﻤﺴﻬﺒﺔ و ﻜذﻝك ﻗﻠﻴﻠﺔ اﻝﺠرﻴﺒﻴﻪ‬ ‫ ﻝم ﻴﺘﺒﻴن إﺼﺎﺒﺔ اﻝﻐدد اﻝﻠﻨﻔﺎوﻴﻪ ﺒﺎﻝﻔﺤص اﻹﻜﻠﻴﻨﻴﻜﻲ‬.‫ ﺤﻤراء اﻝﻠون و ﻻﻤﻌﻪ‬,‫ ﻫذﻩ اﻝﻌﻘﻴدات ﺼﻠﺒﻪ‬.‫ﻤن ﻤﺠﻤوﻋﺔ ﻋﻘﻴدات ﺠﻠدﻴﺔ ﺒﻔروﻩ اﻝرأس ﻤﻨذ ﺤواﻝﻲ ﻋﺎم‬ ‫ و ﺒﺄﺨذ ﻋﻴﻨﻪ ﻤن اﻝﺠﻠد اﻝﻤﺼﺎب أوﻀﺤت وﺠود ﻤﻜﺜف ﻝﻠﺨﻼﻴﺎ اﻝﻠﻨﻔﺎوﻴﻪ اﻝﺒﺎﺌﻴﺔ ﻜﺒﻴرة اﻝﺤﺠم واﻝﻐﻴر ﺴوﻴﻪ ﻤﺘﻐﻠﻐﻠﺔ ﺒﻜل أدﻤﺔ اﻝﺠﻠد‬.‫أو ﺒﺎﻻﺸﻌﻪ اﻝﻤﻘطﻌﻴﺔ‬ .2 ‫ وﺒدت ﺨﻼﻴﺎ اﻝﻌﻴﻨﺔ ﻤﺘوﺴطﺔ اﻻﻴﺠﺎﺒﻴﺔ ﻝﻠﺼﺒﻐﺔ ﺒﻲ ﺴﻲ ال‬.‫ و ﻜذﻝك ﻝوﺤظ اﻨدﻤﺎج اﻝﺠرﻴﺒﺎت ﺒﺈﺴﻬﺎب‬.‫ﻤﻊ وﺠود ﺘﻨوع ﺸﻜﻠﻲ ﺸدﻴد ﺒﻨواة ﻫذﻩ اﻝﺨﻼﻴﺎ‬ ‫ و ﻴﻌﺘﺒر ﻫذا اﻝﻤرﻴض ﺤﺎﻝﺔ ﻓرﻴدة ﻝﻠورم اﻝﻠﻨﻔﺎوى‬.‫ﺒﻬذﻩ اﻝﺼﻔﺎت اﻹﻜﻠﻴﻨﻴﻜﻴﺔ و اﻝﺒﺎﺜوﻝوﺠﻴﺔ ﻴﺘﺒﻴن أﻨﻬﺎ ﻤﻤﺎﺜﻠﺔ ﻝﻠورم اﻝﻠﻨﻔﺎوي اﻝﺠﻠدي اﻷوﻝﻲ ﻝﻠﺨﻼﻴﺎ اﻝﺒﺎﺌﻴﺔ‬ ‫اﻝﻤﺴﻬب ﻝﻠﺨﻼﻴﺎ اﻝﺒﺎﺌﻴﺔ اﻝﻜﺒﻴرة ﻜﻨوع ﻤن اﻝورم اﻝﻠﻨﻔﺎوى اﻝﺠﻠدي اﻷوﻝﻲ ﻝﻤرﻜز اﻝﺠرﻴب‬

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