Transcript Document
HANDOUT 2
B-CELL INFILTRATES
CASE 6: ADDITIONAL FINDINGS
B-cells negative with antibodies to:
•CD5 •CD10 •CD23 •BCL-6 •cyclin D1
DIAGNOSIS PRIMARY CUTANEOUS MARGINAL ZONE LYMPHOMA Synonyms:
•extranodal marginal zone B-cell lymphoma (WHO) •cutaneous immunocytoma (EORTC) •cutaneous follicular hyperplasia with monotypic
plasma cells (Schmid et al Am J Surg Pathol 1995; 19: 12)
CLINICAL
Solitary or multiple tumours Good response to XRT; CR common Frequently relapse Excellent prognosis; 5-year survival >95%
PCMZL and Borrelia burgdorferi A proportion of PCMZL associated with B. burgdorferi infection.
Possibly only in some geographic locations;
•Highlands of Scotland
+ve
•Austria (Graz/Vienna) •USA •Tawain
+ve -ve -ve
PATHOLOGY
Diffuse or periadnexal/perivascular infiltrate Reactive germinal centres common Interfollicular/diffuse neoplastic infiltrate
•marginal zone cells •small lymphocytes •plasmacytoid/plasma cells
Reactive cells
•histiocytes •Eosinphils
Immunophenotype
•CD20, bcl-2 positive •CD5, CD10, CD23, bcl-6, cyclinD1 negative •CD43 +/-
Genetics
•Trisomy 3 in some •t(11;18) not found (c.f. gastric & bronchial MZL)
DIFFERENTIAL DIAGNOSIS
1. Other small B-cell lymphomas 2. Cutaneous B-cell pseudolymphoma
FURTHER READING
Rijlaarsdam et al. Histopathology 1993; 23: 117 Bailey et al. Am J Surg Pathol 1996; 20: 1011 Cerroni et al. Am J Surg Pathol 1997; 21: 1307 Goodlad et al. Am J Surg Pathol 2000; 24: 1279 Wood et al. J Cutan Pathol 2001; 28: 502 Ye et al. Blood 2003; 102: 1012 Chunmei et al. Am J Surg Pathol 2003; 27: 1061
CASE 7: ADDITIONAL FINDINGS
•Stage IE on staging: bone marrow,
CT chest & abdomen
•t(14;18) not found
DIAGNOSIS
PRIMARY CUTANEOUS FOLLICLE CENTRE CELL LYMPHOMA
•(EORTC: although most cases included in this
category display pure diffuse large cell morphology) Synonyms: Grade 3 follicular lymphoma & diffuse large B-cell lymphoma
•(WHO: classifying lesion in this way may result in
over-treatment)
CLINICAL
Solitary plaques, tumours, nodules Head & neck (scalp) Respond to local XRT: CR usual Frequent relapse Excellent prognosis: 5-year survival ~100%
PATHOLOGY
As for nodal follicular lymphoma except:
•Higher proportion of grade 3 lesions +/- DLBCL •Lower incidence of bcl-2 expression (0-60%) •t(14;18) rarely found
PRIMARY CUTANEOUS FOLLICULAR LYMPHOMA High relapse rate but excellent survival
COMPARISON OF OUTCOME WITH STAGE I NODAL FL: Disease status at end of follow-up p<0.01
50 40 30 20 10 0 100 90 80 70 60
% in CR Nodal FL PCFL 15/15 PCFL in complete remission at end of follow up period compared with only 49/87 stage I nodal FL (p<0.01:
c
2 ). Goodlad et al. Am J Surg Pathol 2002
DIFFERENTIAL DIAGNOSIS
1. Other small B-cell lymphomas 2. Cutaneous B-cell pseudolymphoma
FURTHER READING
Garcia et al. Am J Surg Pathol 1986; 10: 454 Yang et al. Am J Surg Pathol 2000; 24: 694 Cerroni et al. Blood 2000: 95; 3922 Franco et al. Am J Surg Pathol 2001; 25: 875 Aguilera et al. Mod Pathol 2001; 14: 828 Goodlad et al. Am J Surg Pathol 2002; 26: 733
CASE 8: ADDITIONAL FINDINGS
Confined to skin on staging CD5, CD23, cyclin D1 negative
DIAGNOSIS
LARGE B-CELL LYMPHOMA OF THE LEG (EORTC) Diffuse large B-cell lymphoma (WHO)
DIFFUSE LARGE B-CELL LYMPHOMA ARISING PRIMARILY IN THE SKIN Probably two subtypes Currently best classified as per EORTC on basis of anatomic location: 1.Primary cutaneous follicle centre cell lymphoma This includes cases with true follicular morphology as treatment and outcome are the same 2. Large B-cell lymphoma of the leg
Primary cutaneous DLBCL on upper body has significantly better prognosis than primary cutaneous B-cell lymphoma on the leg 1.0
Upper body (n=17) 0.8
0.6
0.4
Lower body (n=13) 0.2
0.0
0 Goodlad et al. Am J Surg Pathol; In press [p=0.0047] 50 100 150 Months 200 250 300
COMPARED TO PCFCCL/LBCL ON UPPER BODY, LARGE B-CELL LYMPHOMA OF THE LEG:
•More often female •Older age •More often multiple lesions •Significantly poorer prognosis (5YS <60% c.f.
>95%
•Significantly higher incidence of bcl-2
expression (~100%)
•Less frequent CD10/bcl-6 expression •More often large round cells
(centroblasts/immunoblasts) than large cleaved cells t(14;18) rare at either site
N.B. standard treatment for nodal DLBCL is aggressive CTX (anthracycline based); this would be overtreatment for majority of primary cutaneous DLBCL irrespective of location
DIFFERENTIAL DIAGNOSIS
1. CTCL, large cell types, non-epidermotropic 2. T/NK cell lymphomas
REFERENCES
Vermeer et al. Arch Dermatol 1996 Geelen et al. J Clin Oncol 1998; 16: 2080 Fernandez-Vazquez et al. Am J Surg Pathol 2001; 25: 307 Grange et al. J Clin Oncol 2001; 19: 3602 Fink-Puches et al. Blood 2002; 99: 800 Goodlad et al. Am J Surg Pathol; In press
CASE 9: ADDITIONAL FINDINGS Polyclonal kappa/lambda Polyclonal IgH re-arrangement
DIAGNOSIS
CUTANEOUS B-CELL PSEUDOLYMPHOMA Synonyms: lymphocytoma (benigna) cutis Spiegler-Fendt sarcoid B-cutaneous lymphoid hyperplasia
CUTANEOUS B-CELL PSEUDOLYMPHOMA
Cutaneous infiltrate histologically simulating CBCL Cliincally may also mimic lymphoma
•solitary red nodule/plaque (85-90%) •generalised/multifocal lesions (10-15%)
AETIOLOGY
•Idiopathic •Borrelia burgdorferi •Tattoo (red) •Injection sites •Acupuncture •Trauma •Vaccination •Gold piercing earrings
COMMON THEME IS REACTION TO ANTIGEN
PATHOLOGY
•Diffuse or nodular infiltrate (Grenz zone) •Reactive polytypic B-cells
Often in nodules +/- germinal centres
T-cell rich areas in between
•Prominent vasculature •Macrophages, plasma cells, eosinophils
PRESERVED IMMUNOARCHITECTURE
B-CLH: IMMUNOARCHITECTURE T-cell areas
•
CD3 +
•
few B-cells B-cell nodules
•
CD20, CD23
DIFFERENTIAL DIAGNOSIS: CUTANEOUS INFILTRATES RICH IN SMALL B-CELLS 1. B-cell pseudolymphoma 2. Marginal zone lymhpoma 3. Follicular lymphoma 4. (Secondary involvement by:
• B-CLL • Mantle cell lymphoma)
NATURE OF LYMPHOID FOLLICLES?
1. REACTIVE FOLLICLES
• Found in all three but rare in FL • Appearance as at other sites
Zonation
Tingible body macrophages
Mitotic figures Well formed mantles Uniform CD10/bcl-6 expression by GCCs Bcl-2 negative
2. COLONISED FOLLICLES
•Typical of MZL •Distinct compartments
Reactive GCC: CD10/bcl-6 +ve, bcl-2 -ve
Neoplastic MZ cells: CD10/bcl-6 -ve, bcl-2 +ve 3. NEOPLASTIC FOLLICLES
•Only seen in FL •Same as in nodal FL
No zonation
Monotonous appearance
Few TBMs, MFs (NB grade 3 FL)
Absent/poorly formed mantles
Uniform CD10/bcl-6 staining
Bcl-2 usually +ve (but significant % -ve cases)
NATURE OF INTERFOLLICULAR INFILTRATE?
1. B-CELL PSEUDOLYMPHOMA
• T-cells >> B-cells • NO confluent sheets of B-cells • Polytypic light chain immunohistochemistry • Epidermal changes
e.g. parakeratosis, atrophy, acanthosis, spongiosis 2. MARGINAL ZONE LYMPHOMA
•Clusters/sheets of marginal zone cells •>75% B-cells •Light chain restriction •Aberrant CD43 expression
3. FOLLICULAR LYMPHOMA
•Clusters of CD10/bcl-6+ve B-cells
Useful when bcl-2 –ve
CD10 may be down-regulated
POLYMERASE CHAIN REACTION
Can be helpful but use limited by:
•Most FL are t(14;18) negative •False negatives relatively common •False positive results when very few B-cells •Some CBCPL are monoclonal •Some CBCPL progress to overt lymphoma
THE MOST IMPORTANT DECISION: SHOULD THE PATIENT BE STAGED?
FURTHER READING Ritter et al J Cutan Pathol 1994; 21: 481 Baldassano et al. Am J Surg Pathol 1999; 23: 88 de Leval et al. Am J Surg Pathol 2001; 25: 732 Nihal et al. Hum Pathol 2003; 34: 617