WORKUP. USEFUL IN SELECTED CASES: PET-CT scan Bone marrow biopsy
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1 DIAGNOSIS a WORKUP ESSENTIAL: Review of all slides with at least one paraffin lock representative of the tum should e done y a pathologist with expertise in the diagnosis of primary cutaneous B-cell lymphoma. Reiopsy if consult material is nondiagnostic. Histopathology review of adequate iopsy (punch, incisional, excisional). Adequate immunophenotyping to estalish diagnosis Recommended panel f paraffin section immunohistochemistry: CD20, CD79a, CD3, CD5, CD10, BCL2, BCL6, Ki-67, kappa/lamda, MUM1 USEFUL IN CERTAIN CIRCUMSTANCES: Peripheral lood flow cytometry Additional immunohistochemical studies to estalish lymphoma sutype Paraffin panel: cyclin D1 Molecular genetic analysis to detect: antigen recept gene rearrangements; IgH gene rearrangement y PCR Cytogenetics FISH: t(14;18) c ESSENTIAL: Complete histy and physical examinationincluding complete skin exam CBC, differential, comprehensive metaolic panel LDH Hepatitis B testingd if rituxima considered Chest/adominal/pelvic CT Bone marrow iopsy, if PC-DLBCL, Leg type Pregnancy testing in women of child-earing age (if chemotherapy planned) USEFUL IN SELECTED CASES: PET-CT scan Bone marrow iopsy Consider if PCFCL Optional if PCMZL SPEP/quantitative immunogloulins f PCMZL See Initial Therapy f Primary Cutaneous Marginal Zone Lymphoma (CUTB-2) See Initial Therapy f Primary Cutaneous Follicle Center B-Cell Lymphoma (CUTB-2) See Initial Therapy f Primary Cutaneous B-Cell Lymphoma, Leg Type (CUTB-4) a PC-DLBCL, Leg type: Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg type PCMZL: Primary Cutaneous Marginal Zone B-cell Lymphoma PCFCL: Primary Cutaneous Follicle Center B-cell Lymphoma F non-cutaneous, see Nongastric MALT Lymphoma (NGMLT-1). See Use of Immunophenotyping in Differential Diagnosis of Mature B-cell and T/NK-cell Neoplasms (NHODG-A). c Rule out drug-induced lymphoma. dhepatitis B testing is indicated ecause of the risk of reactivation with immunotherapy + chemotherapy. Tests include hepatitis B surface antigen and ce antiody f a patient with no risk facts. F patients with risk facts previous histy of hepatitis B, add e-antigen. If positive, check viral load and consult with gastroenterologist. Note: All recommendations are categy 2A unless otherwise indicated. Version , 12/22/ National Comprehensive Cancer Netwk, Inc. All rights reserved. These guidelines and this illustration may not e reproduced in any fm without the express written permission of. CUTB-1
2 STAGE f Solitary/regional, T1-2 (Ann Ar Stage IE) INITIAL THERAPY Locegional RT Excision (selected cases g) (selected cases i) PRIMARY CUTANEOUS MARGINAL ZONE OR FOLLICLE CENTER B-CELL LYMPHOMA e Persistent Regional Generalized (extracutaneous ) Generalized (skin only) SECONDARY THERAPY Excision Relapsed, See Injected steroids CUTB-3 Locegional RT Manage as per FOLL-2 Generalized (skin only), T3 Extracutaneous e f g Rituximaj Locegional RT f palliation of symptoms Palliative chemotherapyk such as chlamucilj CVP ± rituxima Manage as per FOLL-2 Unless clinically indicated, additional imaging studies during the course of treatment are not needed. See TNM Classification of Cutaneous Lymphoma other than MF/SS (CUTB-A). may e appropriate if local therapy is contraindicated undesirale. Persistent Note: All recommendations are categy 2A unless otherwise indicated. h i j k Relapsed, See CUTB-3 See Rituxima and Viral Reactivation (NHODG-D) Topicals may include steroids, imiquimod, nitrogen mustard, exarotene. When RT surgical treatment is either not feasile desired. See Treatment References (CUTB-B). In rare circumstances f very extensive, other comination chemotherapy regimens listed in FOLL-B are used. Version , 12/22/ National Comprehensive Cancer Netwk, Inc. All rights reserved. These guidelines and this illustration may not e reproduced in any fm without the express written permission of. CUTB-2
3 PRIMARY CUTANEOUS MARGINAL ZONE OR FOLLICLE CENTER B-CELL LYMPHOMA e RELAPSED DISEASE STAGE f ADDITIONAL THERAPY Solitary/regional, T1-2 (Ann Ar Stage IE) Excision Injected steroids Locegional RT Refracty l Persistent Regional Generalized (extracutaneous ) Generalized (skin only) Manage as per FOLL-2 Relapsed e f h Generalized (skin only), T3 Extracutaneous Rituximaj Locegional RT f palliation of symptoms Palliative chemotherapyk such as chlamucilj CVP ± rituxima Unless clinically indicated, additional imaging studies during the course of treatment is not needed. See TNM Classification of Cutaneous Lymphoma other than MF/SS (CUTB-A). Topicals may include steroids, imiquimod, nitrogen mustard, exarotene. Refracty l Manage as per FOLL-2 Note: All recommendations are categy 2A unless otherwise indicated. j k Persistent See Rituxima and Viral Reactivation (NHODG-D) See Treatment References (CUTB-B). In rare circumstances f very extensive, other comination chemotherapy regimens listed in FOLL-B are used. lrefracty to all previous treatments. Version , 12/22/ National Comprehensive Cancer Netwk, Inc. All rights reserved. These guidelines and this illustration may not e reproduced in any fm without the express written permission of. CUTB-3
4 PRIMARY CUTANEOUS DIFFUSE LARGE B-CELL LYMPHOMA, LEG TYPE STAGE f INITIAL THERAPY SECONDARY THERAPY Solitary regional, T1-2 (Ann Ar Stage IE) m R-CHOP + locegional RT Locegional RT Clinical trial n Persistent Regional Generalized R-CHOP (if not previously received) Manage as per BCEL-5 Locegional RT Manage as per BCEL-5 Generalized (skin only), T3 R-CHOP ± locegional RT Clinical trial Persistent Manage as per BCEL-5 Locegional RT f palliation Radioimmunotherapy Extracutaneous Manage as per BCEL-2 f m n See TNM Classification of Cutaneous Lymphoma other than MF/SS (CUTB-A). F alternate regimens, see BCEL-C. F patients not ale to tolerate chemotherapy. Note: All recommendations are categy 2A unless otherwise indicated. Version , 12/22/ National Comprehensive Cancer Netwk, Inc. All rights reserved. These guidelines and this illustration may not e reproduced in any fm without the express written permission of. CUTB-4
5 TNM CLASSIFICATION OF CUTANEOUS LYMPHOMA OTHER THAN MF/SS a, T T1 T2 T3 N N0 N1 N2 N3 M M0 M1 Solitary skin involvement T1a: a solitary lesion < 5 cm diameter T1: a solitary > 5 cm diameter Regional skin involvement: multiple lesions limited to 1 ody region 2 contiguous ody regions T2a: all--encompassing in a < 15-cm-diameter circular area T2: all--encompassing in a > 15- and < 30-cm-diameter circular area T2c: all--encompassing in a > 30-cm-diameter circular area Generalized skin involvement T3a: multiple lesions involving 2 noncontiguous ody regions T3: multiple lesions involving 3 ody regions No clinical pathologic lymph node involvement Involvement of 1 peripheral lymph node regionc that drains an area of current pri skin involvement Involvement of 2 me peripheral lymph node regionsc involvement of any lymph node region that does not drain an area of current pri skin involvement Involvement of central lymph nodes No evidence of extracutaneous non lymph node Extracutaneous non-lymph node present a This wk was iginally pulished in Blood. Kim YH, Willemze R, Pimpinell Ni, et al, f the ISCL and the EORTC. TNM classification system f primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome: A proposal of the International Society f Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Fce of the European Organization of Research and Treatment of Cancer (EORTC) Blood 2007;110: the American Society of Hematology. F definition of ody regions, see Body Regions f the Designation of T (skin involvement) Categy (CUTB-A 2 of 2). Definition of lymph node regions is consistent with the Ann Ar system: Peripheral sites: antecuital, cervical, supraclavicular, axillary, inguinal-femal, and popliteal. Central sites: mediastinal, pulmonary hilar, paratic, iliac. c Note: All recommendations are categy 2A unless otherwise indicated. Version , 12/22/ National Comprehensive Cancer Netwk, Inc. All rights reserved. These guidelines and this illustration may not e reproduced in any fm without the express written permission of. CUTB-A 1 of 2
6 BODY REGIONS FOR THE DESIGNATION OF T (SKIN INVOLVEMENT) CATEGORY a,,c a Kim YH, Willemze R, Pimpinell Ni, et al, f the ISCL and the EORTC. TNM classification system f primary cutaneous lymphomas other than mycosis fungoides and Sézary syndrome: A proposal of the International Society f Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Fce of the European Organization of Research and Treatment of Cancer (EORTC) Blood 2007;110: c Left and right extremities are assessed as separate ody regions. The designation of these ody regions are ased on regional lymph node drainage patterns. Definition of ody regions: Head and neck: inferi der superi der of clavicles, T1 spinous process. Chest: superi der superi der of clavicles; inferi der inferi margin of ri cage; lateral ders midaxillary lines, glenohumeral joints (inclusive of axillae). Adomen/genital: superi der inferi margin of ri cage; inferi der inguinal folds, anteri perineum; lateral ders mid-axillary lines. Upper ack: superi der T1 spinous process; inferi der inferi margin of ri cage; lateral ders mid-axillary lines. Lower ack/uttocks: superi der inferi margin of ri cage; inferi der inferi gluteal fold, anteri perineum (inclusive of perineum); lateral ders midaxillary lines. Each upper arm: superi ders glenohumeral joints (exclusive of axillae); inferi ders ulnar/radial-humeral (elow) joint. Each lower arm/hand: superi ders ulnar/radialhumeral (elow) joint. Each upper leg (thigh): superi ders inguinal folds, inferi gluteal folds; inferi ders mid-patellae, midpopliteal fossae. Each lower leg/foot: superi ders mid-patellae, mid-popliteal fossae. Note: All recommendations are categy 2A unless otherwise indicated. Version , 12/22/ National Comprehensive Cancer Netwk, Inc. All rights reserved. These guidelines and this illustration may not e reproduced in any fm without the express written permission of. CUTB-A 2 of 2
7 TREATMENT REFERENCES Rituxima Males AV, Advani R, Hwitz SM, et al. Indolent primary cutaneous B-cell lymphoma: experience using systemic rituxima. J Am Acad Dermatol 2008;59: Heinzerling LM, Uranek M, Funk JO, et al. Reduction of tum urden and stailization of y systemic therapy with anti-cd20 antiody (rituxima) in patients with primary cutaneous B-cell lymphoma. Cancer 2000;89: Valencak J, Weihsengruer F, Rapperserger K, et al. Rituxima monotherapy f primary cutaneous B-cell lymphoma: Response and follow-up in 16 patients. Ann Oncol 2009;20: Chlamucil Hoefnagel JJ, Vermeer MH, Jansen PM, et al. Primary cutaneous marginal zone B-cell lymphoma: Clinical and therapeutic features in 50 cases. Arch Dermatol 2005;141: Note: All recommendations are categy 2A unless otherwise indicated. Version , 12/22/ National Comprehensive Cancer Netwk, Inc. All rights reserved. These guidelines and this illustration may not e reproduced in any fm without the express written permission of. CUTB-B
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a DIAGNOSIS WORKUP ESSENTIAL: Review of all slides with at least one paraffin lock representative of the tum should e done y a pathologist with expertise in the diagnosis of primary cutaneous B-cell lymphoma.
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