Cutaneous Presentation of Follicular LymphomasRenato Franco, M.D., Amalia Fernandez-Vazquez, M.D., Manuela Mollejo, M.D., Miguel A. Cruz, M.D.,Francisca I. Camacho, M.D., Juan F. García, M.D., Mercedes Navarrete, B.SC., Miguel A. Piris, M.D.
Department of Biomorphological and Functional Science, Federico II University of Napoli, Italy (RF);Department of Molecular Pathology, Centro Nacional de Investigaciones Oncologicas Carlos III,Majadahonda-Madrid (AFV, FIC, JFG, MN, MAP), Madrid, Spain; and Departments of Pathology (MM)and Oncology (MAC), Virgen de la Salud Hospital, Toledo, Spain
The description of primary cutaneous follicular lym-phoma has raised interest in the differential diagnosisof this versus disseminated follicular lymphoma in-volving the skin. We report here on four cases of StageIV follicular lymphoma, diagnosed in skin biopsy, inwhich cutaneous lesion was the most noticeable fea-ture of clinical presentation. In all cases, the morpho-logical features were superimposed over typical nodalfollicular lymphoma. Apart from classic B-cell mark-ers, they were characterized by CD10 and bcl6 posi-tivity, markers of follicle germinal center cells; andbcl2 expression, with a corresponding t(14;18) trans-location in three of three cases examined. In all fourcases, bone marrow study and clinical staging re-vealed disease that had disseminated since diagnosis.Follow-up showed relapsing cutaneous and nodal dis-ease in two cases. The only difference observed with acontrol group of 10 cases of primary cutaneous follic-ular lymphoma was the absence in this group of t(14;18). Disseminated classical follicular lymphoma has tobe considered in the differential diagnosis of follicularlymphoma presenting in the skin. This series of casessuggests that the presence of t(14;18) could imply theexistence of disease that has disseminated beyond theskin and that cases harboring this translocation couldbe candidates for systemic polychemotherapy.
The morphological features and clinical behavior ofB-cell lymphomas presenting in the skin arescarcely recognized in the lymphoma classificationcurrently in use, the REAL classification (1), whichhas led to the publication of a first proposal ofcutaneous lymphoma by the EORTC group (2). Oneof the groups included in this category, so-calledcutaneous follicular lymphoma (CFL), has fueled adebate on the features and differential nature ofthis entity. Although the molecular, phenotypical,and morphological traits of these tumors have yetto be fully defined, the concept that some bona fideB-cell lymphomas originating in the lymphoid fol-licle may clinically present as cutaneous tumorsseems to be clearly established (2– 4). Thus the skincould be involved by follicular lymphoma (FL), inthe form of a secondary lesion (sCFL), the expres-sion of disseminated disease, or as a primary lesion(pCFL), localized initially in the skin and usually fora long period of time (2–5).
Systemic FL is usually a disseminated neoplasm,with over two thirds of cases being in Stage III or IVat diagnosis (2). It recapitulates both the cytologicaland immunohistochemical features of secondaryfollicles, and neoplastic cells frequently show a spe-cific translocation, t(14;18). It may also involve theskin in the form of specific lesions, sCFL, and doesso in almost 4% of cases (4).
The existence of primary cutaneous B-cell lym-phoma, defined as a B-cell non-Hodgkin’s lym-phoma primarily occurring in and remaining con-fined to the skin for a period of at least 6 months,has now been widely accepted (2, 5, 7–21). Accord-ing to the EORTC, primary cutaneous follicularlymphoma (pCFL) shows a relatively good out-come, rarely disseminating to extracutaneous sites.This could support the selection of local treatmentof the tumor (2, 4, 19, 22, 23). The real frequency ofpCFL and its morphological and molecular charac-teristics are, however, a matter of controversy, asare its differential diagnosis versus marginal zone
lymphoma in the skin (7, 24) and disseminated FLinvolving the skin.
In the course of a review of cases of cutaneousB-cell lymphoma, we noticed the existence of agroup of four cases of FLs that, diagnosed on thebasis of skin biopsies, have shown widespread dis-ease since diagnosis, with clinical signs of progres-sion in at least two cases. Because this suggests thatthese tumors must be recognized independently ofpCFL, we reviewed the main features of this groupof FLs presenting in the skin.
MATERIALS AND METHODS
Patients and Tissue SamplesTumor specimens of four cutaneous biopsies
with FL were obtained from routine files of theVirgen de la Salud Hospital, Toledo, Spain, corre-sponding to a period from 1990 to 2000. All patientswere under study for cutaneous lesions that at bi-opsy showed FL histology. From the onset of thedisease, the staging of all the patients included inthe series showed widespread involvement, includ-ing bone marrow infiltration. All specimens werereevaluated, including initial cutaneous lesions, thestaging bone marrow biopsies, secondary cutane-ous lesions, or restaging bone marrow biopsies per-formed during the follow-up. Cases were classifiedinto three grades, based on numbers of large cells(centroblasts), according to the criteria of Mannand Bernard (25)
ImmunohistochemistryAll immunostaining techniques were performed
in paraffin-embedded tissue sections, using a pre-vious step of heat-induced antigen retrieval tech-nique for all antibodies. Thus, before incubationwith the primary antibody, slides were heated in apressure cooker for 3 minutes in a solution of 0.01mol/L sodium citrate.
After incubation with the antibody, immunode-tection was performed with biotinylated antimouseimmunoglobulins, followed by peroxidase-labeledstreptavidin (LSAB-DAKO, Glostrup, Denmark)with diaminobenzidine chromogen as substrate. Allimmunostaining was performed using the Tech-mate 500 (DAKO) automatic immunostaining de-vice. The antibodies used for immunohistochemi-cal study were directed against B-cell markers CD20and CD79a, T-cell marker CD3; specific markers ofmantle-cell lymphoma CD5, cyclin D1, and IgD;germinal center markers such as CD10 and bcl6;marker of dendritic cells CD23; oncoproteins p53and bcl2; and proliferative marker MIB1. The datacorresponding to the antibodies used are shown inTable 1.
The presence of positivity was quantified as apercentage. In particular, CD20, CD10, bcl6, andbcl2 were scored as positive if the majority of tu-moral cells showed a distinct reactivity. MIB1 ex-pression was scored as low Ki67 when the percent-age of positive tumoral cells was �30%; moderatewhen between 30% and 60%; and high when �60%of tumoral cells were positive.
Polymerase Chain ReactionDNA isolated by conventional methods from pe-
ripheral blood (Case 3), bone marrow and periph-eral blood (Case 2), and cryopreserved (�80°C) tis-sue of skin biopsies was analyzed for t(14;18) bypolymerase chain reaction (PCR). PCR amplifica-tion of p53 Exon 8 (249 bp) was used to assess thesuitability of DNA extracts, using a volume of 100ng.
PCR was performed to detect the t(14;18) at themajor breakpoint region (MBR). PCR was per-formed with 0.1 �g of purified DNA, which wassubjected to 35 cycles of PCR amplification usingMBR and JH consensus primer. The MBR and JHprimers have been described elsewhere (21). Tenpercent of PCR products was size-fractionated on1.5% agarose gel. Specimens were observed in ul-traviolet B light. The presence of a band between100 and 250 base pairs (bp) was considered positivefor translocation.
ControlsA group of 10 cases of pCFL was used as the
control group for the study of t(14;18). These caseswere selected according to clinical findings (com-puted tomography scan, ultrasonography, andbone marrow biopsies without signs of lymphomainvolvement for at least 6 months after diagnosis),morphological signs (follicular pattern of growth,germinal center cytology), immunophenotypicalcriteria (bcl6 and CD10 positivity and the presenceof follicular dendritic cells), and suitability of theDNA extracted from paraffin-embedded tissue forPCR analysis. Samples were from a larger collection
TABLE 1. Characteristics of Antibodies
Antigen Clone (Manufacturer) Incubation Time Dilution
CD20 L26 (DAKO) 40 min 1:50CD79a JCB117 (DAKO) 40 min 1:25CD23 MHM6 (DAKO) 40 min 1:25CD10 56C6 (Novocastra) Overnight 1:25CD3 Polyclonal (DAKO) 40 min 1:50CD43 DFT1 (DAKO) 40 min 1:50CD5 4C7 (Novocastra) 40 min 1:10CiclD1 DC56 (DAKO) 40 min 1:100P53 DO7 (DAKO) 40 min 1:50Bcl2 124 (DAKO) 40 min 1:25Bcl6 PG-B6P (DAKO) 40 min 1:10MIB1 MIB1 (Immunotech) 40 min 1:50
914 Modern Pathology
of cutaneous pCBCL obtained from the files of theSpanish hospitals integrated in the Spanish Lym-phoma Club. These cases of pCFL belong to a largerseries, whose results concerning the frequency ofIgH rearrangement and t(14;18) translocation havealready been published (26).
RESULTS
Clinical featuresThe main clinical data are shown in Table 2.
Case 1This was a female 61-year-old showing several
erythematous lesions of �0.5 cm on the left eye-brow (Fig. 1) and in the sternal region, with othersmaller ones spread over the trunk. No other symp-toms were present. Twelve months after the initialsymptoms, a biopsy of the lesions was performedand showed the features of FL. Laboratory exami-nation did not provide significant results. Clinicalexamination revealed significant axillary and ingui-nal adenopathy (node size, �1.0 cm), and radiolog-ical examination (computed tomography scan andultrasonography) showed hepatosplenomegaly.Bone marrow biopsy also showed a neoplastic in-filtration. The patient was classified as having StageIV FL.
She was treated with polychemotherapy and hada complete remission. She was well with the excep-tion of nonspecific remittent lymphadenopathy fora period of 50 months, when three erythematousinfiltrated lesions were observed in the posterolat-eral region of the right thigh. Bone marrow biopsywas negative. X-ray exams were negative. Biopsyshowed FL in this case. The patient began to receivelocal radiotherapy.
Fifteen months later, another papule was ob-served in the exterior upper left leg, and the biopsyagain showed FL. Finally, 14 months later, anotherlesion positive for FL was observed in the antero-
lateral region of the left leg. Radiotherapy wasperformed.
Eight years after diagnosis, the patient is alive,with disease restricted to the skin.
Case 2This female 33-year-old presented a solitary pap-
ule of the scalp, surrounded by an annular ery-thema. No other symptoms were present. One yearafter the initial symptom, a skin biopsy showedlesions diagnosed as FL. Laboratory examinationwas not significant. Clinical and x-ray examinationresults were negative for other site locations. Bonemarrow biopsy showed FL infiltration. A t(14;18)was then detected in peripheral blood and bonemarrow lymphocytes. The patient had a completeclinical remission, with persistence of t(14;18) inperipheral blood.
Thirty-two months later, she showed weight loss(5 kg) and irregularities of the menstrual cycle. Ret-roperitoneal lymphadenopathies and a peritonealmass were found at this time by CT scan. This time,the patient was treated with polychemotherapy,and she underwent clinical and molecular remis-sion. Now, 60 months after the initial diagnosis, sheis alive and well.
Case 3This 49-year-old woman presented a cutaneous
nodule on the right shoulder and a smaller one inthe sternal region. No symptoms were present. Tenmonths after the initial symptoms, cutaneous bi-opsy showed an FL. Subsequent clinical examina-tion showed significant axillary and inguinallymphadenopathies. CT scan and ultrasonographydid not show any significant alterations. Bone mar-row biopsy showed neoplastic infiltration. t(14;18)was detected in bone marrow lymphocytes. Thepatient was considered to be in Stage IV of thedisease. After 5 months of polychemotherapy, shestill has persistent disease.
TABLE 2. Main Clinical Data
Case
Site Primitive Lesion(Duration in Months of
Clinical Symptomsbefore Biopsy)
Other Sites of Disease atStaging
Therapy afterSurgicalExcision
Follow-Up (Tissues Infiltrated andTime from the Diagnosis, in
Months)
Status (Monthsfrom Diagnosis)
1 Right eyebrow sternalregion (10)
Liver and spleen; axillaryLNs; bone marrow
CT Bone marrow (0, 7); liver, spleenand axillary LNs (0, 7); skin,right thigh (71); skin, left leg(88); skin, left leg (91)
AWD (108)
2 Scalp (12) Bone marrow CT Bone marrow (0, 7); intercavo-aortic LNs and peritoneum (48)
CR (60)
3 Right shoulder (10) Neck and axillary LNs;bone marrow
CT Bone marrow (0); neck andaxillary LNs (0)
AWD (5)
4 Frontal region (60) Bone marrow RT Bone marrow (0) CR (36)
All cases were Stage IV and female.CT, chemotherapy; RT, radiotherapy; AWD, alive with disease; CR, complete remission; LN, lymph node.
Cutaneous Presentation of Follicular Lymphomas (R. Franco et al.) 915
Case 4A female 74-year-old presented a 5-year-old cu-
taneous nodule with slow growth in the right fron-tal region, associated with smaller peripheral pap-ules. B symptoms were not present. Skin biopsyshowed FL. Laboratory examinations were not sig-nificant. Clinical and x-ray examinations were neg-ative. Bone marrow biopsy showed an infiltration oflymphoma. The patient was considered to be atStage IV.
In consideration of her age and of the absence ofother lesions, the patient was submitted to localradiotherapy. After 7 months, the patient finishedradiotherapy, and cutaneous lesions disappeared.The patient is now alive and well 3 years afterdiagnosis.
Histological Findings
Skin samplesIn all cases, we observed a middermal and sub-
cutaneous diffuse and/or nodular infiltration bygerminal center B cells, composed of confluentnodules of variable size. The tumoral cells wererepresented in variable amounts in each case bysmall, cleaved cells and large cells, cleaved or non-cleaved, and with a prominent nucleolus. In partic-ular, we observed prevalent centrocytes (Grade IFL) in Case 1; a mixture of centrocytes and centro-blasts (Grade II FL) in Cases 2 and 3; and a preva-lent population of centroblasts (Grade III FL) in thefourth case. A variable component of reactiveT-cells was also observed in each case. No reactivefollicles were observed. The papillary dermis wasspared in all cases in the typical Grenz zone fash-ion, as well as was the epidermis. No epidermotro-pism was observed (Table 3 and Fig. 2).
No appreciable changes were observed in theconsecutive biopsies of these patients, except for atransformation of histological grade in Case 1, inwhich a transition to Grade II was observed duringrelapses.
Bone marrow biopsyBone marrow biopsies performed for the staging
of disease showed a paratrabecular, nodular infil-tration by FL in all cases, whereas in Case 4, thepresence of diffuse bone marrow involvement wasalso observed. The cytology was composed mainly
of small B cells (Fig. 3). Follow-up bone marrowbiopsies in Case 1 showed persistent infiltration,despite treatment.
Immunohistochemical findingsNeoplastic cells showed a B-cell immunopheno-
type (CD20�, CD79a�, CD3� CD43�) in skin spec-imens and bone marrow biopsies in all cases. CD10,bcl2, and bcl6 were positive in all cases. Bcl6 ex-pression was observed both in the follicular andinterfollicular compartment. All cases were nega-tive for cyclin D1 and CD5. p53 was always nega-tive. MIB1 expression was low to intermediate (Ta-ble 3 and Fig. 4). In all cases, neoplastic follicleswere outlined by the presence of aggregates ofCD23� follicular dendritic cells.
Bone marrow biopsy showed CD20 and bcl2-positive paratrabecular nodules (Fig. 3b).
PCR findingsIn the group of disseminated FL presenting in the
skin, PCR study detected the presence of t(14;18) inall three cases in which DNA was available for mo-lecular study. This study was performed in the cu-taneous samples in two of three cases, whereas inthe third case, it was done using peripheral bloodand bone marrow. The quality of the DNA extractedin Case 4 was unsuitable for molecular study (Table3 and Fig. 5). None of the 10 cases of pCFL showedt(14;18).
DISCUSSION
We described four cases of Stage IV FL presentingin the skin. All four of these cases showed bonemarrow infiltration at initial diagnosis, and two ofthem displayed lymph node involvement. Despitethis, the clinical follow-up revealed a relatively in-dolent clinical behavior, with relapses in two of fourcases. To the best of our knowledge, cases such asthese, disseminated FL in which the first clinicalmanifestation was cutaneous infiltration, have notbeen reported previously, and they may raise diffi-culties in terms of differential diagnosis betweensCFL and pCFL. Cases so far reported of FL withcutaneous infiltration antecede the recognition thatB-cell lymphoma may debut as a purely cutaneoustumor, differentiating them from rare cases of con-current involvement of lymph node and skin at
TABLE 3. Main Morphological and Immunohistochemical Findings in Secondary Cutaneous Follicular Lymphoma
Case Grade CD20 CD10 Bcl2 Bcl6 P53 Ki67 t(14;18)
1 I � � � � � Low �2 II � � � � � Low �3 II � � � � � Low �4 III � � � � � Intermediate ND
ND, not determined.
916 Modern Pathology
diagnosis (27) or from secondary cutaneous in-volvement in the course of the disease (5, 27).
Cutaneous lymphomas represent the secondmost important group of extranodal lymphomasafter gastrointestinal lymphoma (2, 17, 20). Untilrecent years, no real distinction between pCFL andsCFL was made, and they were all classified, andtherefore treated, according to the scheme used fornodal non-Hodgkin’s lymphoma (28, 29). So-calledprimary cutaneous lymphoma, because of its pecu-liar clinicopathological features, has recently beenthe subject of specific proposals for classification (2,7, 20, 23). The aim of recently introduced classifi-cations, such as the Revised European AmericanLymphoma classification (1) and that by the Euro-pean Organization for Research and Treatment (2),is to differentiate distinct nosological entities withpeculiar clinical characteristics. In the staging andtreatment of patients with cutaneous lymphoma,the usefulness of distinguishing lymphoma re-stricted to the skin from other generalized lympho-mas involving the skin is of great practicalimportance.
We have shown here that disseminated FL de-buted with only symptomatic and often prolongedcutaneous lesions, the initial diagnosis being per-formed with a skin biopsy. Only after the initialdiagnosis of lymphoma was made did the staging ofthe patient reveal widespread disease, includingbone marrow infiltration in all cases (2, 6). Thisemphasizes the usefulness of including a bone mar-row biopsy in the staging of cutaneous lymphomabefore making a diagnosis of primary cutaneouslymphoma.
Disseminated FL has a 5-year survival probabilityof 30 to 50% and needs to be treated with generalpolychemotherapy. This contrasts with data show-ing that in pCFL, the probability of survival is wellabove 90% after a 10-year follow-up (2, 4). Thisdifference in survival probability and treatment un-derscores the importance of finding molecular orimmunophenotypic markers that can distinguish
between these two different clinical presentationsof FL. Although pCFLs display the same morphol-ogy and CD10 or bcl6 expression as nodal FL, theymay differ in the incidence of t(14;18), which hasonly rarely been reported in pCFL (4, 12, 24, 31).Thus, in our series, t(14;18) was present in three ofthree cases analyzed, in contrast with its absence in10 of 10 of the cases of pCFL included here forcomparison. The absence of a t(14;18) in pCFL isconsistent with the findings by Cerroni et al. (4),who recently described a series of 15 pCFL thatwere diagnosed and staged according to classicalcriteria. Other authors show the presence of thist(14;18) in a proportion of patients; thus, Volk-
FIGURE 1. Nodular lesion at left eyebrow.
FIGURE 2. Hematoxylin-eosin staining. Nodular pattern of dermalinfiltration of lymphoma (A, 10.6�; B, 250�) with representation ofcentrocytes and centroblasts (C, 630�; D, 1000�).
FIGURE 3. A, paratrabecular bone marrow infiltration by lymphoma(hematoxylin-eosin staining, 200�). B, bcl2 positivity of bone marrowneoplastic cells (200�).
Cutaneous Presentation of Follicular Lymphomas (R. Franco et al.) 917
enandt et al. (30) describe this translocation in 1case of 10 centroblastic and centrocytic lympho-mas, and Yang et al. (31) describe a very high fre-quency of t(14;18) in pCFL (6/15 cases). Whether
these differences could be attributable to variationsin the procedure for clinical staging of the patientsor the conditions used in molecular study remainsto be answered, but in any case, the data hereshowed are consistent with the findings reported byCerroni et al. (4) correlating the presence of t(14;18)with disseminated extracutaneous disease.
Nevertheless, all of these data suggest that itwould be advisable to perform additional biologicalstudies on larger groups of patients with differenttypes of cutaneous lymphoma to better define theboundary between primary and secondary cases (2).
To conclude, we underline the fact that FL, whendiagnosed in the skin, may correspond to cutane-
FIGURE 4. Immunohistochemistry. A, CD20 (200�). B, CD3 (200�). C, CD10 (200�). D, bcl2 (200�). E, bcl6 (200� and detail, 450�). F, CD23(200�). G, IgD (200� and detail, 450�). H, MIB1 (200�).
FIGURE 5. Polymerase chain reaction results. Cases 1 to 3: secondarycutaneous follicular lymphoma. Cases 4 to 13: primary cutaneousfollicular lymphoma. The band indicates the presence of t(14;18) inCases 1 to 3. C�, positive control. C�, negative control.
918 Modern Pathology
ous preferential involvement by disseminated FLs.The data collected here seem to support the interestof recognizing these tumors, given that they haveshown a tendency to involve extracutaneous sitesand relapse in nodal and other locations. A partic-ular contribution to clinical staging was made bythe performance of bone marrow biopsy. Our find-ings also indicate the clinical relevance of the pres-ence of a t(14;18), which was always found to beassociated with disseminated extracutaneous dis-ease in this study.
REFERENCES
1. Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML,et al. A revised European-American classification of lym-phoid neoplasms: a proposal from the International Lym-phoma Study Group. Blood 1994;84:1361–92.
2. Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti S,et al. EORTC classification for primary cutaneous lympho-mas: a proposal from the Cutaneous Lymphoma StudyGroup of the European Organization for Research and Treat-ment of Cancer. Blood 1997;90:354 –71.
3. Bastion Y, Berger F, Bryon PA, Felman P, Ffrench M, CoiffierB. Follicular lymphomas: assessment of prognostic factors in127 patients followed for 10 years. Ann Oncol 1991;2S:123–9.
5. Dabski K, Banks PM, Winkelmann RK. Clinicopathologicspectrum of cutaneous manifestations in systemic follicularlymphoma: a study of 11 patients. Cancer 1989;64:1480 –5.
6. Armitage JO, Weisenburger DD. New approach to classifyingnon-Hodgkin’s lymphomas: clinical features of the majorhistologic subtypes. Non-Hodgkin’s Lymphoma Classifica-tion Project. J Clin Oncol 1998;16:2780 –95.
8. Baldassano MF, Bailey EM, Ferry JA, Harris NL, Duncan LM.Cutaneous lymphoid hyperplasia and cutaneous marginalzone lymphoma: comparison of morphologic and immuno-phenotypic features. Am J Surg Pathol 1999;23:88 –96.
9. Beljaard RC, van Beek P, Willemze R. Relation between ex-pression of adhesion molecules and clinical behaviour incutaneous follicle centre cell lymphomas. J Am Acad Der-matol 1997;37:34 – 40.
10. Cerroni L, Kerl H. Diagnostic immunohistology: cutaneouslymphomas and pseudolymphomas. Semin Cutan Med Surg1999;18:64 –70.
11. Cerroni L, Signoretti S, Hofler G, Annessi G, Putz B, Lack-inger E, et al. Primary cutaneous marginal zone B-cell lym-phoma: a recently described entity of low-grade malignantcutaneous B-cell lymphoma. Am J Surg Pathol 1997;21:1307–15.
12. Cerroni L, Volkenandt M, Rieger E, Soyer HP, Kerl H. bcl-2protein expression and correlation with the interchromo-somal 14; 18 translocation in cutaneous lymphomas andpseudolymphomas. J Invest Dermatol 1994;102:231–5.
13. Delia D, Borrello MG, Berti E, Pierotti MA, Biassoni D, Gi-annotti R, et al. Clonal immunoglobulin gene rearrange-
ments and normal T-cell receptor, bcl2, and c-myc genes inprimary cutaneous B-cell lymphomas. Cancer Res 1989;49:4901–5.
14. Faure P, Chittal S, Gorguet B, Caveriviere P, Brousset P,Viraben R, et al. Immunohistochemical profile of cutaneousB-cell lymphoma on cryostat and paraffin sections. Am JDermatopathol 1990;12:122–33.
15. Garbe C, Stein H, Dienermann D, Orfanos CE. Borrelia Burg-dorferi associated cutaneous B cell lymphoma: clinical andimmunohistologic characterization of four cases. J Am AcadDermatol 1991;125:373– 86.
17. Isaacson PG, Norton AJ. Cutaneous lymphoma. In: IsaacsonPG, Norton AJ, editors. Extranodal lymphoma. London:Churchill Livingstone; 1994. p. 172.
18. Kempf W, Dummer R, Burg G. Approach to lymphoprolif-erative infiltrates of the skin. The difficult lesions. Am J ClinPathol 1999;111(1 Suppl 1):S84 –93.
19. Sepp N, Weyer K, Haun M, Zelger B, Thaler J, Faber V, et al.Differentiation of primary and secondary cutaneous B-celllymphoma by Southern blot analysis. Am J Clin Pathol 1996;106:749 –57.
20. Slater DN. MALT and SALT: the clue to cutaneous B-celllymphoproliferative disease. Br J Dermatol 1994;131:557– 61.
21. Willemze R, Beljaards RC, Meijer CJ, Rijlaarsdam JR. Classi-fication of primary cutaneous lymphomas. Historical over-view and perspectives. Dermatology 1994;189(Suppl 2):8 –15.
22. Kerl H, Cerroni L. The morphologic spectrum of cutaneousB-cell lymphomas. Arch Dermatol 1996;132:1376 –7.
23. Kurtin PJ, Di Caudo DJ, Habermann TM, Chen MG, Su WP.Primary cutaneous large cell lymphomas. Morphologic, im-munophenotypic, and clinical features of 20 cases. Am J SurgPathol 1994;18:1183–91.
24. Willemze R, Rijlaarsdam JU, Meijer CJ. Are most primarycutaneous B-cell lymphomas “marginal cell lymphomas”?Br J Dermatol 1995;133:950 –2.
25. Mann RB, Bernard CW. Criteria for the cytological subclas-sification of follicular lymphomas: a proposed alternativemethod. Hematol Oncol 1983;1:187–92.
26. Franco R, Fernandez-Vazquez A, Rodriguez-Peralto JL, Bel-las C, López-Ríos F, Sáez A, et al. Cutaneous follicular B-celllymphoma. Description of a series of 18 cases. Am J SurgPathol 2001;25:875– 83.
27. Garcia CF, Weiss LM, Warnke RA, Wood GS. Cutaneousfollicular lymphoma. Am J Surg Pathol 1986;10:454 – 63.
28. The Non-Hodgkin’s Lymphoma Pathologic ClassificationProject. National Cancer Institute sponsored study of classi-fication of non-Hodgkin’s lymphomas: summary and de-scription of a working formulation for clinical usage. Cancer1982;49:2112–35.
29. Stansfeld AG, Diebold J, Kapanaci Y, Kelenyi G, Lennert K,Mioduszewska O, et al. Updated Kiel classification for lym-phomas. Lancet 1988;1:292–3.
30. Volkenandt M, Cerroni L, Rieger E, Soyer HP, Koch O, Wie-necke R, et al. Analysis of the 14; 18 translocation in cuta-neous lymphomas using the polymerase chain reaction. JCutan Pathol 1992;19:353– 6.
31. Yang B, Tubbs RR, Finn W, Carlson A, Peatty J, Hsi ED.Clinicopathologic reassessment of primary cutaneous B-celllymphomas with immunophenotypic and molecular geneticcharacterization. Am J Surg Pathol 2000;24:694 –702.
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