HANDOUT 2

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HANDOUT 2
B-CELL INFILTRATES
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CASE 6 ADDITIONAL FINDINGS

• B-cells negative with antibodies to
• CD5
• CD10
• CD23
• BCL-6
• cyclin D1

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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)

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CLINICAL
Solitary or multiple tumours Good response to
XRT CR common Frequently relapse Excellent
prognosis 5-year survival gt95
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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

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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

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• Immunophenotype
• CD20, bcl-2 positive
• CD5, CD10, CD23, bcl-6, cyclinD1 negative
• CD43 /-
• Genetics
• Trisomy 3 in some
• t(1118) not found (c.f. gastric bronchial MZL)

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DIFFERENTIAL DIAGNOSIS

• Other small B-cell lymphomas
• Cutaneous B-cell pseudolymphoma

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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
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CASE 7 ADDITIONAL FINDINGS

• Stage IE on staging bone marrow, CT chest
  abdomen
• t(1418) not found

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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)

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CLINICAL
Solitary plaques, tumours, nodules Head neck
(scalp) Respond to local XRT CR usual Frequent
relapse Excellent prognosis 5-year survival
100
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PATHOLOGY

• As for nodal follicular lymphoma except
• Higher proportion of grade 3 lesions /- DLBCL
• Lower incidence of bcl-2 expression (0-60)
• t(1418) rarely found

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PRIMARY CUTANEOUS FOLLICULAR LYMPHOMA
High relapse rate but excellent survival
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COMPARISON OF OUTCOME WITH STAGE I NODAL
FL Disease status at end of follow-up
15/15 PCFL in complete remission at end of
follow-up period compared with only 49/87 stage I
nodal FL (plt0.01 c2). Goodlad et al. Am J Surg
Pathol 2002
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DIFFERENTIAL DIAGNOSIS

• Other small B-cell lymphomas
• Cutaneous B-cell pseudolymphoma

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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
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CASE 8 ADDITIONAL FINDINGS
Confined to skin on staging CD5, CD23, cyclin D1
negative
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DIAGNOSIS
LARGE B-CELL LYMPHOMA OF THE LEG (EORTC) Diffuse
large B-cell lymphoma (WHO)
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DIFFUSE LARGE B-CELL LYMPHOMA ARISING PRIMARILY
IN THE SKIN

• Probably two subtypes
• Currently best classified as per EORTC on basis
  of anatomic location
• 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

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Primary cutaneous DLBCL on upper body has
significantly better prognosis than primary
cutaneous B-cell lymphoma on the leg
Goodlad et al. Am J Surg Pathol In press
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• 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 lt60 c.f.
  gt95
• Significantly higher incidence of bcl-2
  expression (100)
• Less frequent CD10/bcl-6 expression
• More often large round cells (centroblasts/immunob
  lasts) than large cleaved cells
• t(1418) rare at either site

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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
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DIFFERENTIAL DIAGNOSIS

• CTCL, large cell types, non-epidermotropic
• T/NK cell lymphomas

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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
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CASE 9 ADDITIONAL FINDINGS
Polyclonal kappa/lambda Polyclonal IgH
re-arrangement
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DIAGNOSIS
CUTANEOUS B-CELL PSEUDOLYMPHOMA
Synonyms lymphocytoma (benigna)
cutis Spiegler-Fendt sarcoid B-cutaneous
lymphoid hyperplasia
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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)

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• AETIOLOGY
• Idiopathic
• Borrelia burgdorferi
• Tattoo (red)
• Injection sites
• Acupuncture
• Trauma
• Vaccination
• Gold piercing earrings
• COMMON THEME IS REACTION TO ANTIGEN

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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

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B-CLH IMMUNOARCHITECTURE

• T-cell areas
• CD3
• few B-cells

• B-cell nodules
• CD20, CD23

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DIFFERENTIAL DIAGNOSIS CUTANEOUS INFILTRATES
RICH IN SMALL B-CELLS

• B-cell pseudolymphoma
• Marginal zone lymhpoma
• Follicular lymphoma
• (Secondary involvement by
• B-CLL
• Mantle cell lymphoma)

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NATURE OF LYMPHOID FOLLICLES?

• 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

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• 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)

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NATURE OF INTERFOLLICULAR INFILTRATE?

• B-CELL PSEUDOLYMPHOMA
• T-cells gtgt 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
• gt75 B-cells
• Light chain restriction
• Aberrant CD43 expression

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• 3. FOLLICULAR LYMPHOMA
• Clusters of CD10/bcl-6ve B-cells
• Useful when bcl-2 ve
• CD10 may be down-regulated

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POLYMERASE CHAIN REACTION

• Can be helpful but use limited by
• Most FL are t(1418) negative
• False negatives relatively common
• False positive results when very few B-cells
• Some CBCPL are monoclonal
• Some CBCPL progress to overt lymphoma

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THE MOST IMPORTANT DECISION SHOULD THE PATIENT
BE STAGED?
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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