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) +ve•USA -ve•Tawain -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 lymphomas2. Cutaneous B-cell pseudolymphoma

FURTHER READING

Rijlaarsdam et al. Histopathology 1993; 23: 117Bailey et al. Am J Surg Pathol 1996; 20: 1011Cerroni et al. Am J Surg Pathol 1997; 21: 1307Goodlad et al. Am J Surg Pathol 2000; 24: 1279Wood et al. J Cutan Pathol 2001; 28: 502 Ye et al. Blood 2003; 102: 1012Chunmei 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

0

10

20

30

40

50

60

70

80

90

100

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15/15 PCFL in complete remission at end of follow-up period compared with only 49/87 stage I nodal FL (p<0.01: 2). Goodlad et al. Am J Surg Pathol 2002

COMPARISON OF OUTCOME WITH STAGE I NODAL FL:Disease status at end of follow-up

DIFFERENTIAL DIAGNOSIS

1. Other small B-cell lymphomas

2. Cutaneous B-cell pseudolymphoma

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

FURTHER READING

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 subtypesCurrently best classified as per EORTC on basis of anatomic location:

1.Primary cutaneous follicle centre cell lymphomaThis 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 leg1.0

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0 50 150100 200 250 300

Months

Upper body (n=17)

Lower body (n=13)

[p=0.0047]

Goodlad et al. Am J Surg Pathol; In press

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) cutisSpiegler-Fendt sarcoidB-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 centresT-cell rich areas in between

•Prominent vasculature•Macrophages, plasma cells, eosinophils

PRESERVED IMMUNOARCHITECTURE

B-cell nodules•CD20, CD23

T-cell areas•CD3 +•few B-cells

B-CLH: IMMUNOARCHITECTURE

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 -veNeoplastic MZ cells: CD10/bcl-6 -ve, bcl-2 +ve

3. NEOPLASTIC FOLLICLES•Only seen in FL•Same as in nodal FL

No zonationMonotonous appearanceFew TBMs, MFs (NB grade 3 FL)Absent/poorly formed mantlesUniform CD10/bcl-6 stainingBcl-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