The Cutaneous Lymphoid Proliferations E-Book

Cynthia M. Magro

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 1632

Veröffentlichungsjahr: 2015

Beschreibung

A masterful and thorough revision of the only single-source, authoritative reference on cutaneous lymphoproliferative disease.

• Classic reference for unsurpassed coverage of lymphocytic infiltrates of the human skin
• Covers a broad spectrum of topics ranging from the role of the immune system in the pathogenesis of cutaneous lymphocytic infiltrates to one describing   the immunohistochemica nd molecular aspects of lymphoid neoplasia. 
• Each chapter contains an extensive array of  ‘clinical vignettes’ clearly showing the application of principles and treatment techniques discussed in the chapter
• Presents a succinct and logical approach to the diagnosis of most cutaneous lymphocytic infiltrates and discusses the  interplay between the immune system in  the propagation of lymphocytic infiltrates focusing on the role of iatrogenic and endogenous immune dysregulation. The molecular and cytogenetic basis of lymphoid neoplasia is considered in great detail.
• Contains hundreds of full-color, high-quality clinical and histologic photographs, with over 200 new images in the new edition

Leseprobe

The Cutaneous Lymphoid Proliferations

A Comprehensive Textbook of Lymphocytic Infiltrates of the Skin

Second Edition

Cynthia M. Magro MD

Professor of Pathology and Laboratory Medicine Department of Pathology, Cornell University Weill Cornell Medicine New York, NY, USA

A. Neil Crowson MD

Clinical Professor of Dermatology, Pathology, and Surgery Director of Dermatopathology at the University of Oklahoma and Regional Medical Laboratory President of Pathology Laboratory Associates Tulsa, OK, USA

Martin C. Mihm MD

Clinical Professor of Pathology and Dermatology, Harvard Medical School Director of Melanoma Program, Dermatology, Brigham and Women’s Hospital Co-Director of Melanoma Program, Dana-Farber and Brigham and Women’s Cancer Center Director, Mihm Cutaneous Pathology Consultative Service Brigham and Women’s Hospital Boston, MA, USA

Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada

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ISBN: 9781118776261

Cover images: middle left and bottom right – courtesy of Dr. Shivakumar Subramaniyam

CONTENTS

Acknowledgments

CHAPTER 1 Introduction to the Classification of Lymphoma

Kiel Lukes–CollinsWorking Formulation classifications

WHO, REAL, EORTC, and the Combined WHO/EORTC classifications

Summary

References

Appendix: Definitions of key terms and techniques

Plasma cell markers

Natural killer cell-associated markers

Cytotoxic protein markers

B cell markers

Myelomonocytic markers including dendritic cell markers

Follicular dendritic cell markers

Special techniques

Summary of antibodies, clones, and dilutions

CHAPTER 2 The Therapy of Cutaneous T Cell Lymphoma

Introduction

Diagnostic work-up and staging procedures

CTCL therapies

Goals of therapy in advanced-stage CTCL

Extracorporeal photopheresis (ECP)

Interferons

Retinoids

Immunotoxins

Monoclonal antibodies

Histone deacetylase inhibitors (HDACi)

Antibody drug conjugates (ADC)

Cytotoxic chemotherapy

Investigational therapies

TLR agonists and cytokines

Allogeneic hematopoietic stem cell transplantation (allo-HSCT)

References

CHAPTER 3 Molecular Analysis in Cutaneous Lymphoid Proliferation

Introduction

Immunoglobulin and T cell receptor structure

PCR design for determination of clonality

Detection of PCR products for clonality

Evaluation of results

The value and utility of molecular diagnostics in primary cutaneous lymphomas

Limitations of clonality assessment by PCR

Case vignettes

References

CHAPTER 4 Benign Lymphocytic Infiltrates

Introduction

Spongiotic and eczematous dermatitis

Other spongiotic/eczematous tissue reactions

Other causes of subacute eczematous dermatitis

Interface dermatitis: cell-poor vacuolar interface dermatitis

Interface dermatitis: lichenoid pattern

Diffuse and nodular lymphocytic dermal infiltrates without atypia

Diffuse and nodular lymphocytic infiltrates associated with autoimmune disease

References

CHAPTER 5 Reactive Lymphomatoid Tissue Reactions Mimicking Cutaneous T and B Cell Lymphoma

Lymphomatoid drug eruptions

Molecular profile of lymphomatoid drug eruptions

Pathogenetic basis of lymphomatoid drug reactions

Reactive lymphomatoid lesions encountered in lesions of collagen vascular disease

Angiomatous Variants of Pseudolymphoma

Case vignettes

References

CHAPTER 6 Precursor Lesions of Cutaneous T Cell Lymphoma

Cutaneous T cell lymphoid dyscrasia

Large plaque parapsoriasis

Hypopigmented interface T cell dyscrasia: a unique indolent T cell dyscrasia

Pigmented purpuric dermatosis (PPD)

Pityriasis lichenoides

Idiopathic erythroderma (pre-Sézary syndrome)

Syringolymphoid hyperplasia with alopecia

Folliculotropic T cell lymphocytosis/pilotropic T cell dyscrasia

Idiopathic follicular mucinosis/alopecia mucinosa

Keratoderma-like T cell dyscrasia

Atypical lymphocytic lobular panniculitis

Case vignettes

References

CHAPTER 7 Marginal Zone Lymphoma and Other Related Post Germinal Center B Cell Lymphoproliferative Disorders of The Skin

Marginal zone lymphoma

Blastic marginal zone lymphoma

Epidermotropic marginal zone lymphoma

Castleman disease

Primary cutaneous plasmacytoma

Primary cutaneous light chain associated cutaneous amyloidosis

Case vignettes

References

CHAPTER 8 Primary Cutaneous Follicle Center Cell Lymphoma

Clinical features

Pathology

Phenotypic profile

Molecular studies

Pathogenesis

Cytogenetics

Case vignettes

Additional molecular and cytogenetic study

References

CHAPTER 9 Primary Cutaneous Diffuse Large B Cell Lymphoma Including the Leg Type and Precursor B Cell Lymphoblastic Lymphoma

Primary cutaneous diffuse large B cell lymphoma

Systemic diffuse large B cell lymphomas with a propensity to involve the skin

Case vignettes

Additional light microscopic, phenotypic, molecular, cytogenetic studies

References

CHAPTER 10 Intravascular Lymphoma

Clinical features

Light microscopic findings

Phenotypic profile

Molecular and cytogenetic studies

Pathogenesis

Differential diagnosis

Intravascular anaplastic large cell lymphoma

Benign intravascular proliferations of histiocytes and reactive T cells

Case vignette

References

CHAPTER 11 Cutaneous Mantle Cell Lymphoma

Clinical features

Light microscopic findings

Phenotypic profile

Molecular studies

Cytogenetic profile

Pathogenesis

Case vignettes

Additional molecular and cytogenetic studies

References

CHAPTER 12 Mycosis Fungoides and Sézary Syndrome

Definition

Mycosis fungoides

Sézary syndrome and erythrodermic mycosis fungoides

Large cell transformation of mycosis fungoides

Extracutaneous involvement in mycosis fungoides

Case vignettes

References

CHAPTER 13 Cd30-Positive Lymphoproliferative Disorders Including Lymphomatoid Papulosis, Borderline Cd30-Positive Lymphoproliferative Disease, Anaplastic Large Cell Lymphoma, and T-Cell-Rich Cd30-Positive Large B Cell Lymphoma

Introduction

Lymphomatoid papulosis

CD8+ lymphomatoid papulosis, including the type D variant

Type E lymphomatoid papulosis (Case vignette 15)

Borderline CD30-positive lymphoproliferative disorders (type C LYP) (Case vignette 9)

Lymphomatoid papulosis with a rearrangement on chromosome 6p25.3

Cutaneous anaplastic large cell lymphoma

Small cell ALCL

Additional unusual histologic variants of anaplastic large cell lymphoma

Breast-implant-associated anaplastic large cell lymphoma

Intravascular anaplastic large cell lymphoma

Sarcomatoid anaplastic large cell lymphoma (Case vignette 14)

CD30-positive large B cell lymphoma

Case vignettes

References

CHAPTER 14 CD4+ peripheral T cell lymphoma, not otherwise specified, including primary cutaneous CD4+ small/medium-sized pleomorphic T cell lymphoma

Introduction

Primary cutaneous CD4+ small/medium-sized pleomorphic T cell lymphoma

CD30-negative large cell T cell lymphoma

Cutaneous follicular helper T cell lymphoma

Overview of overall prognosis of primary cutaneous peripheral T cell lymphoma, unspecified

Evolution of the nomenclature of primary cutaneous CD4+ small/medium-sized pleomorphic T cell lymphoma

Case vignettes

References

CHAPTER 15 Subcutaneous Panniculitis-Like T Cell Lymphoma

Clinical features

Morphology

Phenotype

Molecular studies

Differential diagnosis

Case vignettes

References

CHAPTER 16 CD8 T Cell Lymphoproliferative Disease of the Skin

Overview

Introduction

Classification of primary CD8+ cutaneous T cell lymphomas

Histomorphology of primary cutaneous CD8+ T cell lymphoma: primary cutaneous aggressive epidermotropic CD8+ cytotoxic T cell lymphoma, and CD8+ variants of peripheral T cell lymphoma, NOS, including primary cutaneous CD8+ granulomatous T cell lymphoma

CD8 variant of lymphomatoid papulosis and other related CD30-positive T cell lymphoproliferative disorders of CD8 subtype

Light microscopic findings

Indolent CD8 positive lymphoid proliferation of the face and other body sites including acral surfaces

CD8 prolymphocytic leukemia

CD8 pseudolymphoma related to underlying HIV disease

Drug-associated CD8+ pseudolymphoma

Actinic reticuloid as a unique form of CD8+ pseudolymphoma

Case vignettes

References

CHAPTER 17 Nasal and Related Extranodal Natural Killer Cell/T Cell Lymphomas and Blastic Plasmacytoid Dendritic Cell Neoplasm

Introduction

Biology of NK and NK-like T cells

NK/T-cell lymphoma

Nasal NK/T cell lymphoma

Nasal type NK/T cell lymphoma

Aggressive NK cell lymphoma

Role of Epstein–Barr virus in the evolution of NK/T cell lymphomas

Blastic plasmacytoid dendritic cell neoplasm

CD56-positive γ δ lymphoma involving the subcutaneous fat

Chronic granular lymphocytosis/large granular cell leukemia

Natural killer-like CD4+ T cell lymphoma

EBV-associated NK/T cell lymphomas of the elderly

Hydroa vaccineforme (HV)-like lymphoma

Cutaneous intravascular NK T cell lymphoma

Case vignettes

References

CHAPTER 18 Primary Cutaneous

γ δ

T Cell Lymphoma

Introduction

Case vignettes

Additional supplemental figures

References

CHAPTER 19 Epstein–Barr Virus-Associated Lymphoproliferative Disease

Introduction

Hydroa vacciniforme-like EBV-associated T cell lymphoproliferative disease/mosquito bite hypersensitivity

EBV+ cutaneous B cell lymphoproliferative disorder of the elderly (Case vignette 4, Figures 19.15, 19.16, 19.17, 19.18, 19.19, 19.20, and 19.21)

EBV-associated mucocutaneous ulcer

EBV + T cell lymphoproliferative disease of the elderly

General principles regarding EBV-associated lymphomagenesis

Pathogenetic link between EBV-associated B cell lymphoma and iatrogenic immune dysregulation related to either methotrexate or cyclosporine

Case vignettes

References

CHAPTER 20 Hodgkin Lymphoma of the Skin

Clinical features

Subtypes of Hodgkin lymphoma

Case vignettes

References

CHAPTER 21 Chronic Lymphocytic Leukemia of B Cell and T Cell Prolymphocytic Leukemia

B cell chronic lymphocytic leukemia

T cell prolymphocytic leukemia

Case vignettes

References

CHAPTER 22 Adult T Cell Leukemia/Lymphoma

Clinical features

Pathology

Phenotypic studies

Pathogenesis

Infective dermatitis of childhood

Case vignettes

References

CHAPTER 23 Angioimmunoblastic Lymphadenopathy/Angioimmunoblastic T Cell Lymphoma

Clinical features

Light microscopic findings

Phenotypic studies

Molecular studies

Pathogenesis

Case vignettes

References

CHAPTER 24 Lymphomatoid Granulomatosis

Introduction

Clinical features (see Table 24.1)

Histopathology

Histogenesis

Clonality studies

Differential diagnosis (see Table 24.2)

Treatment

Case vignette

References

CHAPTER 25 Cutaneous Infiltrates of Myeloid Derivation

Introduction

Leukemia cutis

Clonal histiocytopathy syndromes

Histiocytopathy of factor XIIIA perivascular dermal dendritic cell origin

Case vignettes

References

Index

EULA

List of Tables

Chapter 1

Table 1.1

Table 1.2

Table 1.3

Table 1.4

Table 1.5

Table 1.6

Table 1.7

Table 1.8

Chapter 2

Table 2.1

Table 2.2

Chapter 4

Table 4.1

Table 4.2

Table 4.3

Table 4.4

Table 4.5

Table 4.6

Table 4.7

Table 4.8

Table 4.9

Chapter 6

Table 6.1

Table 6.2

Table 6.3

Table 6.4

Table 6.5

Chapter 7

Table 7.1

Table 7.2

Table 7.3

Chapter 8

Table 8.1

Chapter 9

Table 9.1

Table 9.2

Chapter 10

Table 10.1

Chapter 11

Table 11.1

Chapter 12

Table 12.1

Table 12.2

Table 12.3

Table 12.4

Table 12.5

Table 12.6

Chapter 13

Table 13.1

Table 13.2

Table 13.3

Chapter 14

Table 14.1

Table 14.2

Chapter 15

Table 15.1

Chapter 16

Table 16.1

Table 16.2

Table 16.3

Chapter 17

Table 17.1

Table 17.2

Table 17.3

Table 17.4

Chapter 18

Table 18.1

Chapter 19

Table 19.1

Chapter 20

Table 20.1

Chapter 21

Table 21.1

Table 21.2

Chapter 22

Table 22.1

Table 22.2

Table 22.3

Chapter 23

Table 23.1

Chapter 24

Table 24.1

Table 24.2

Chapter 25

Table 25.1

List of Illustrations

Chapter 3

Figure 3.1

Violaceous plaque involving the forehead.

Figure 3.2

IgH gene rearrangement

. A distinct band is seen, suggesting the presence of monoclonal B cell population.

Figure 3.3

TCR gamma tube A

. A distinct band is seen, indicative of a monoclonal T cell population.

Figure 3.4

TCR gamma tube B

. A distinct band is seen, indicative of a monoclonal T cell population.

Figure 3.5

Gene scanning images.

Figure 3.6

Gene scanning images.

Figure 3.7

The patient developed progressive annular erythematous patches and plaques despite drug cessation, making the diagnosis of a drug-associated reversible T cell dyscrasia less likely.

Figure 3.8

TCR gamma tubes A and B

. A similar band is seen in both skin biopsies 1 and 2, suggestive of presence of the same monoclonal T cell population in each biopsy. A different band is seen in the peripheral blood (a). She eventually developed a CD30+ secondary anaplastic large cell lymphoma with an identical T cell clone as that noted in prior biopsies, indicating the progression of her disease to a tumor-stage mycosis fungoides (b).

Figure 3.9

TCR gamma analysis revealed a monoclonal T cell population

. Despite the identification of T cell clonality in his skin biopsy and the rather striking clinical presentation reminiscent of mycosis fungoides, there was full resolution of the plaque with drug cessation only over a period of 12 months with no subsequent recurrence. Interestingly, the patient had developed evidence of peripheral blood T cell clonality with the same T cell clone identified in the peripheral blood as that noted in his skin sample. While he has had no recurrence of his skin rash, the patient continued for several years to have a detectable T cell clone in his peripheral blood. He is well and otherwise asymptomatic.

Figure 3.10

The first panel is from a specimen morphologically compatible with pityriasis lichenoides, whereas the second and third panels are from two different blocks of a lesion of anaplastic large cell lymphoma and mycosis fungoides. The identical restricted T cell repertoire is present in all three samples, despite the varied morphology.

Figure 3.11

TCR beta analyses reveal a clonal process in all three samples, with identical molecular profiles. A comparison made with an earlier specimen showed similar results. The molecular results of one of the samples are illustrated, showing a dominant T cell clone in a minimal polyclonal background.

Figure 3.12

TCR beta analyses of two separate biopsies (a and b) show a monoclonal T cell population with preservation of T-cell clonotypes at different sites.

Chapter 4

Figure 4.1

Delayed dermal hypersensitivity.

The hallmarks are those of perivascular lymphocytic infiltrates in intimate apposition to the blood vessels of the sampled dermis. Other common accompanying features include papillary dermal edema, mild spongiosis, and tissue eosinophilia.

Figure 4.2

Low-grade eczematous dermatitis with directed migration of lymphocytes into the suprapapillary plates.

This pattern of lymphocyte migration to involve specific epithelial structures associated with preferential processing of antigen is typical for type IV hypersensitivity reactions. This biopsy, one of pityriasis rosea, defines a classic form of low-grade eczematoid hypersensitivity, presumably due to viral antigen.

Figure 4.3

Photoallergic lichenoid dermatitis.

If typical lesions of lichen planus manifesting a striking photodistribution are noted, consideration of a photoallergic dermatitis with lichen planus-like features should be considered. Such cases may show significant lymphoid atypia. However, mycosis fungoides in a restricted distribution to sun-exposed skin is virtually unheard of.

Figure 4.4

Erythema multiforme.

There is a destructive interface dermatitis with prominent keratinocyte necrosis. The unaltered thickness of the epidermis and only slight alterations of the stratum corneum are characteristic for a skin lesion of short duration, as is typical in the setting of erythema multiforme. In contrast, in most lesions of cutaneous T cell lymphoma, features of chronicity are present.

Figure 4.5

Gottron's papule.

Gottron's papule is a distinctive finding in dermatomyositis. The characteristic morphology comprises erythematous scaly plaques localized over the dorsal aspects of the interphalangeal and metacarpal phalangeal joints.

Figure 4.6

Lichen planus.

The lesions of lichen planus are characterized by violaceous flat-topped papules that have a tendency to coalesce, assuming an annular configuration.

Figure 4.7

Lichen planus.

The findings are those of classic lichen planus. Note the hypergranulosis and hyperkeratosis with an accompanying band-like lymphocytic infiltrate lying in apposition to the basal layer of the epidermis. Associated destructive epithelial changes are present. In mycosis fungoides it would be most unusual to find this pattern of uniform hypergranulosis; the exception would be those cases of mycosis fungoides that fall under the appellation of lichenoid mycosis fungoides.

Figure 4.8

Oral lichen planus

. Classic intraoral lichen planus with features of Wickham's striae.

Figure 4.9

Lichen planus.

There is lymphocyte satellitosis around necrotic keratinocytes, indicative of an immune-based dermatosis, namely, one of cellular cytotoxicity.

Figure 4.10

Subacute cutaneous lupus erythematosus

. The biopsy is one of an interface dermatitis showing lichenoid and cell-poor areas of interface dermatitis with attendant epithelial attenuation consistent with subacute cutaneous lupus erythematosus. The higher-power magnification emphasizes the sequelae of the immune-based destructive interface process, namely, one of prominent colloid body formation with epithelial attenuation.

Figure 4.11

Subacute cutaneous lupus erythematosus

. There is confluent photodistributed erythema. Such cases raise a list of differential diagnostic considerations including dermatomyositis, subacute cutaneous lupus erythematosus, and a drug-induced photoallergic or photoirritant dermatitis. The patient in this case had anti-Ro anbodies in the setting of subacute cutaneous lupus erythematosus associated with calcium-channel blocker therapy.

Figure 4.12

Polymorphous light eruption.

There is striking papillary dermal edema. Such findings would be most unusual in the realm of cutaneous T or B cell dyscrasias.

Figure 4.13

Discoid lupus erythematosus.

There is a destructive lymphocyte-rich interface dermatitis involving the hair follicle, compatible with discoid lupus erythematosus.

Figure 4.14

Discoid lupus erythematosus.

There is a distinctive pattern of lymphocyte apposition to the hair follicle with attendant follicular destruction and hyperkeratosis. The haphazard pattern of lymphocyte migration characteristic of pilotropic T cell dyscrasia is not seen.

Figure 4.15

Morphea.

There is deep-seated dermal sclerosis with a supervening interstitial and perivascular lymphocytic and plasmacellularis infiltrate. The plasma cells are found in close apposition to nerves, a finding typical for morphea. Also note the extension of the fibrosis into the septae. Interlobular septal fibroplasia is seen in three primary settings: morphea, necrobiosis lipoidica, and erythema nodosum.

Chapter 5

Figure 5.1

Lymphocytoma cutis.

This patient developed a nodular lesion on the tip of her nose. She was on antidepressants for many years. Both the clinical presentation and histomorphology are characteristic for lymphocytoma cutis.

Figure 5.2

Interstitial granulomatous drug reaction.

This patient developed an erythematous symmetrical rash involving the upper back. The biopsy showed an interstitial histiocytic and lymphocytic infiltrate with variable lymphoid atypia. The patient was on an ACE inhibitor. While the clinical presentation was unusual, the findings are most compatible with an interstitial granulomatous drug reaction.

Figure 5.3

Palisading granulomatous drug reaction.

In this image one sees infiltrative violaceous plaques involving the trunk. Such cases raise strong diagnostic consideration, both clinically and histologically, of mycosis fungoides. In regard to the palisading granulomatous drug reaction, the most commonly implicated drugs are ACE inhibitors and/or calcium-channel blockers.

Figure 5.4

There is an interface dermatitis in association with a superficial angiocentric lymphocytic infiltrate.

Figure 5.5

Higher power magnification reveals pleomorphism of the angiocentric infiltrate. The cells are in the 20–30 μm size range. Given the temporal association between initiation of drug therapy and lesional onset, a diagnosis was rendered of lymphomatoid drug reaction. A lymphomatoid hypersensitivity reaction may be a sign of underlying endogenous immune dysregulation, which in this case is clearly in the context of the patient’s peripheral T cell lymphoma. The patient died 6 months later of her lymphoma. Lymphoid atypia does not always mean lymphoma; however, it may suggest an iatrogenic and/or endogenous immune dysregulatory state.

Figure 5.6

The biopsy shows striking lymphocytic infiltration of the panniculus. However, the pattern of infiltration is a nodular one, which is unusual in the realm of neoplastic infiltrates that involve the fat. More characteristically, a diffuse pattern of infiltration is observed in panniculitis-like T cell lymphoma.

Figure 5.7

Phenotypic studies reveal that the infiltrate exhibits a zonation pattern with respect to lymphocyte subset composition. Peripherally, the cells are dominated by CD3-positive T cells while central zones of nodularity are dominated by CD20-positive B lymphocytes. This particular orderly pattern of distribution of lymphocyte subpopulations is characteristic for reactive lymphoid hyperplasia. In essence, it recapitulates the B-cell-rich germinal center and paracortical T cell distribution of a normal lymph node. Illustrated in Figure 5.7a is CD20; illustrated in Figure 5.7b is CD3.

Figure 5.8

A dense nodular infiltrate assumes a greater density of infiltration toward the lesional base. One could argue that such changes are more in keeping with marginal zone lymphoma. However, there are exceptions as exemplified by this case. One might be more cautious regarding a definitive interpretation as lymphocytoma cutis and recommend careful clinical follow-up.

Figure 5.9

Higher-power magnification reveals that the infiltrate is predominated by small mature lymphocytes.

Figure 5.10

Phenotypic studies demonstrate a composition comprising a mixture of T and B cells. As noted with the earlier case, there is a distinctive zonation pattern in the distribution of the T and B cells. The CD3-positive T cells are distributed peripherally, while the B cells are positioned more centrally in the nodules, as illustrated in Figure 5.11 (CD3 immunostain)

Figure 5.11

The B cells assume a central disposition within the nodules (CD20 immunostain)

Figure 5.12

The biopsy shows a band-like lymphocytic infiltrate lying in intimate apposition to the epidermis. There are destructive epithelial changes with prominent lymphocyte satellitosis around necrotic keratinocytes.

Figure 5.13

Higher-power magnification reveals that a number of the lymphocytes have an atypical cerebriform appearance. Occasional eosinophils are also present in the background.

Figure 5.14

Higher-power magnification shows cerebriform lymphocytes within the epidermis. However, note the concomitant destructive epithelial changes.

Figure 5.15

There is no loss of CD7, which would be an unusual finding in the realm of cutaneous T cell lymphoma.

Figure 5.16

This CD4 stain shows that the majority of the lymphocytes are of the CD4 subset.

Figure 5.17

The biopsy shows a superficial and deep nodular infiltrate lying in close apposition to blood vessels, hair follicles, and the straight eccrine duct.

Figure 5.18

Higher-power magnification reveals that the infiltrate is composed of a mixture of small mature lymphocytes with interposed larger cells in the 15–20 μm size range.

Figure 5.19

The infiltrate is dominated by T cells. Illustrated is a CD43 preparation.

Figure 5.20

The epidermis showed changes of lichen simplex chronicus. The superficial vascular plexus demonstrated striking injurious alterations. A prominent angiocentric infiltrate is noted involving the superficial and deep dermis.

Figure 5.21

The infiltrate is predominated by small mature lymphocytes, some of which have a cerebriform appearance.

Figure 5.22

A few of the larger cells are CD30 positive. CD30 positivity is not uncommon in lymphomatoid hypersensitivity reactions. Characteristically, the CD30-positive cells are found in the superficial dermis as opposed to endogenous CD30 lymphoproliferative disease (i.e., lymphomatoid papulosis), where the CD30 cells are also apparent in the deeper aspects of the biopsy.

Figure 5.23

The biopsy shows an eczematoid reaction characterized by psoriasiform hyperplasia with directed migration of lymphocytes into the epidermis, and vertically oriented collagen bundles.

Figure 5.24

There are a number of small cerebriform lymphocytes within the epidermis and dermis. There is no enhanced atypia with regard to the cells within the epidermis compared to those in the dermis. In addition, a significant large cell component is not identified.

Figure 5.25

The biopsy shows a diffuse pandermal lymphocytic infiltrate.

Figure 5.26

Higher-power examination reveals an infiltrate comprising small mature lymphocytes with admixed cohesive collections of histiocytes.

Figure 5.27

The CD3 preparation shows extensive staining throughout the dermis for CD3.

Figure 5.28

The CD20 preparation shows a number of positive-staining B lymphocytes, including in the context of those assuming a nodular staining pattern at the base of the biopsy specimen.

Figure 5.29

There is preservation of CD62L expression.

Figure 5.30

There is preservation of CD7 expression.

Figure 5.31

T cell clonality can be seen in lesions of T-cell-rich lymphocytoma cutis. Molecular studies reveal a dominant T cell peak amid a polyclonal background in panel B compatible with monoclonal T cell population. The case is illustrated in Figures 5.25, 5.26, 5.27, 5.28, 5.29, and 5.30. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 5.32

The molecular profile is an excellent example of how lymphomatoid drug reactions can produce a molecular profile that simulates lymphoma. In this case, the clinical and light microscopic findings were compatible with a drug-associated photoreaction manifesting photoirritant changes, an interface dermatitis, and a concomitant markedly atypical lymphomatoid vascular reaction, the latter showing numerous CD30-positive cells with preservation of CD7 expression. The molecular profile showed a monoclonal T cell population amid a polyclonal background (base-pair fragment sizes of 253, 257, 181). The clonally restricted populations are likely largely derived from those around the blood vessels. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 5.33

The molecular studies showed a monoclonal population of T cells in a minimal polyclonal background (dominant base-pair peaks of 178, 272, and 258), recapitulating a molecular profile seen in T cell lymphoma. The molecular profile is from a case of drug-associated follicular mucinosis. The patient’s underlying inherent immune dysregulatory state likely contributed to the development of this unusual clonally restricted T-cell-rich drug reaction. Patients with CLL are known hyper-responders to other stimuli; the most published examples of this concept are in the context of lymphomatoid responses that develop with insect bite reactions (see Chapter 11). The facial rash resolved with IDEC cessation. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 5.34

The molecular profile is from this case of drug-associated reversible T cell dyscrasia. Light microscopically, the biopsy was quite characteristic for a lymphomatoid drug reaction showing a superficial nodular angiocentric lymphocytic infiltrate with numerous transformed cells around the vessels, minimal epidermal involvement, and sparing of the mid- and deeper dermis. There were no phenotypic abnormalities. However, the molecular studies showed a monoclonal T cell population in a minimal polyclonal background (dominant T cell clones with base pair sizes of 260, 271, 191, and 195). While a clonally restricted drug reaction was favored, additional biopsies were advised if there was lesional persistence after 8–9 months off the implicated drug or drugs. The rash eventually resolved. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 5.35

In the setting of collagen vascular disease, a restricted T cell repertoire that is maintained over time can be observed. It does not necessarily imply a neoplastic process or lymphoid dyscrasia per se. It is established that a limited number of T cell epitopes leading to emergence of oligoclonal T cell populations is seen in the setting of autoimmune disease. The two molecular profiles performed a few weeks apart from two different sites in this young child with lichen sclerosus et atrophicus, morphea overlap are an excellent depiction of this concept. Specifically, there is an oligoclonal pattern amid a polyclonal background (the base pair size of the dominant peaks are listed). While there is commonality between the two profiles, there is an additional dominant clone in the latter sample (i.e., base pair size of 191) that is not present in the earlier case. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 5.36

The molecular studies show two distinct populations of T cells amid a polycolonal background. Clonality can occur in lesions of lupus profundus. The biopsy shows a striking interstitial lymphocytic infiltrate within the fat. Germinal centers are also present, although not illustrated. From a phenotypic perspective, the infiltrate is CD4 dominant. In atypical lymphocytic lobular panniculitis and panniculitis-like T cell lymphoma, germinal centers would be very uncommon and there would not be a dominance of CD4 lymphocytes, as noted here although not illustrated. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 5.37

The patient presents with a striking eruption characterized by distinctive brownish-red plaques remarkable for their symmetrical distribution on the arms and trunk. (Source: Photographs courtesy of Dr. David Roy, Mississippi.)

Chapter 6

Figure 6.1

Hypopigmented cutaneous T cell dyscrasia.

The patient is an 8-year-old African American girl with a longstanding history of waxing and waning plaques on the face and axillae. The biopsy showed features of the so-called hypopigmented interface variant of cutaneous lymphoid dyscrasia. Such cases may be interpreted as representing hypopigmented MF. There is indeed a continuum between the hypopigmented interface variant of cutaneous lymphoid dyscrasia and hypopigmented mycosis fungoides. (

Source

: Dr. Kelly Gallina. Reproduced with permission.)

Figure 6.2

Pigmented purpuric dermatosis.

The patient is a 68-year-old man with a longstanding history of pigmented purpuric dermatosis. Illustrated are classic lesions of pigmented purpura. Note the petechial quality of the lesions.

Figure 6.3

Pigmented purpuric dermatosis.

The patient illustrated in Figure 6.2 developed progressive disease eventuating in MF.

Figure 6.4

Lichen aureus.

This is a classic clinical image of lichen aureus. Note the large bronze plaque. There are cases of MF that have been presaged by lesions of lichen aureus; the original index case described in the literature was in the context of a patient with a longstanding plaque of lichen aureus.

Figure 6.5

The patient is a 36-year-old man with a longstanding history of pigmented purpura who subsequently developed MF. The patient’s biopsy is illustrated histologically in Figures 6.24. 6.25, 6.26, and 6.27. The two images (a,b) are more within the spectrum of pigmented purpuric dermatosis. The eruption was widespread, an important clue to clonal variants of pigmented purpuric dermatosis and to those cases at greater risk for progression to MF.

Figure 6.6

Pityriasis lichenoides chronica.

The patient is a 9-year-old girl with a 2–3 year history of scaly plaques manifesting truncal, axillary, and extremity localization. The biopsy findings were consistent with pityriasis lichenoides. (

Source

: Dr. Kelly Gallina. Reproduced with permission.)

Figure 6.7

Pityriasis lichenoides chronica.

The patient is an 8-year-old boy with multiple recurrent scaly oval lesions involving the genital area, lower trunk, and legs. The combined clinical and light microscopic findings are consistent with pityriasis lichenoides. (

Source

: Mohammed Diab. Reproduced with permission.)

Figure 6.8

Pityriasis lichenoides chronica.

Multiple persistent scaly lesions compatible with pityriasis lichenoides. (Source: Dr. Kelly Gallina. Reproduced with permission.)

Figure 6.9

Syringolymphoid hyperplasia with alopecia. Localized asymptomatic plaque with prominence of follicles, although without hair and associated dryness.

Figure 6.10

Alopecia mucinosa.

Scaly plaque on the face compatible with alopecia mucinosa.

Figure 6.11

The patient is a 26-year-old man who presented with a history of waxing and waning plaques on the forehead for 2 years. The biopsy findings were compatible with alopecia mucinosa with evidence of a TCR-

β

gene rearrangement.

Figure 6.12

Atypical lymphocytic lobular panniculitis.

The patient is a 36-year-old man (see micrographs in Figures 6.17, 6.18, 6.19, 6.20, and 6.21) with waxing and waning plaques primarily involving the thighs. (

Source

: Mohammed Diab. Reproduced with permission.)

Figure 6.13

The patient is a 42-year-old female with a history of recurrent panniculitis since high school. She had several biopsies and laboratory evaluations in the past (1988 and 2003). Since her last biopsy she continues to have episodic flares, where treatment with Motrin has alleviated the symptoms. She presented on January 2005 with a recent episode. The thigh area showed multiple erythematous nodules (see Case vignette 8). (

Source

: Dr. David Knox. Reproduced with permission.)

Figure 6.14

The biopsy shows hyperplasia with small zones of epithelial attenuation with overlying orthohyperkeratosis and parakeratosis. At this power one can see a band-like lymphocytic infiltrate and very striking infiltration of the epidermis by lymphocytes, although with a largely intact basal layer, indicating that the process is in essence an epidermotropic one rather than representing a true immunologically mediated interface dermatitis.

Figure 6.15

There is colonization of the epidermis by lymphocytes. Note the superficially disposed small Langerhans-cell-rich microabscesses, almost reminiscent of a Pautrier’s microabscess, but different by virtue of a composition that includes numerous Langerhans cells. There is no edema associated with this microvesicle, which separates it from a spongiotic microvesicle of eczema.

Figure 6.16

The extent of intraepidermal lymphocyte migration can be striking. It is not uncommon to see foci where the degree of intraepidermal lymphocytic infiltration exceeds the discernible keratinocyte population. The pattern of migration is largely a passive one, hence warranting the designation of epidermotropism.

Figure 6.17

This biopsy is characteristic for PLC. Note the small zones of epidermal effacement in concert with prominent migration of lymphocytes. While there is focal spinous layer dyskeratosis, there is no true destructive interface dermatitis. Also characteristic is the overlying parakeratotic scale imbued with leukocytes, which can in some cases be neutrophilic in nature. This is an important point since the presence of intracorneal neutrophils could be misconstrued as being compatible with psoriasis.

Figure 6.18

Higher-power magnification in this case reveals the classic cytomorphology of the infiltrating cells, which is a small mature lymphocyte with some degree of nuclear contour irregularity. It is not uncommon to see cells with a cerebriform appearance, although large cerebriform cells, especially when exceeding the degree of dermal-based lymphoid atypia, would be uncommon and would suggest progression to MF.

Figure 6.19

The striking tendency for lymphocyte aggregation to involve the superficial layers of the epidermis is typical.

Figure 6.20

There are Langerhans-cell-rich “nonspongiotic” microvesicles manifesting localization within the superficial layers of the epidermis.

Figure 6.21

This photomicrograph emphasizes the pattern of epidermal migration that is really best described as being truly epidermotropic. The cells passively migrate into the epidermis with only a minimal epidermal response.

Figure 6.22

The lymphocytes may show a substantial loss of CD7 expression.

Figure 6.23

Although the CD4 and CD8 results are variable in many instances, the abnormal clonally restricted cells in the epidermis are likely of the CD4 subset, while the CD8 cells have a countersurveillance regulatory function. It is quite possible that if there is an attenuation in the CD8 response then a predominance of the clonally restricted CD4 lymphocytes may lead to disease progression, specifically in the context of transition into MF. Illustrated is CD4.

Figure 6.24

A biopsy was performed showing a superficial perivascular lymphocytic infiltrate with associated red cell extravasation. There is focal migration of lymphocytes into the epidermis. Overall, the pattern of intraepidermal lymphocyte migration is an epidermotropic one.

Figure 6.25

Higher magnification reveals that the lymphocytes exhibit some degree of nuclear atypia as defined by nuclear hyperchromasia and nuclear contour irregularity. A few of the cells have a frankly cerebriform appearance.

Figure 6.26

A CD7 preparation reveals a reduction in expression with virtually no cells in the epidermis or dermis manifesting any staining.

Figure 6.27

Over the ensuing years the eruption became more extensive, the patient developed supervening pruritus. A biopsy showed a greater degree of lymphocytic infiltration with more extensive epidermotropism and greater atypia compatible with MF.

Figure 6.28

The molecular studies were performed on earlier biopsies and the patient’s more recent skin lesions. The biopsies revealed clonality and more specifically the same persistent T cell clones over a 3-year period, including biopsies of classic PPD and those more consonant with a diagnosis of MF, clearly indicative of lesional progression from the same clonally restricted T cell population. This identification of persistent T cell clones is the hallmark of cutaneous lymphoid dyscrasia. While there is monoclonality apparent in all three separate specimens procured over different time periods, the most recent biopsy is that of fully evolved MF showing a stronger peak compared to the monoclonal T cell population identified in the earlier biopsies depicted in 6.28b. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.29

The biopsy shows a moderately dense infiltrate within the interstitium of the fat. Most of the infiltrates emanate from zones of angiocentric lymphocytic infiltration.

Figure 6.30

Higher-power magnification reveals a mixture of small- and intermediate-sized mature lymphocytes with some degree of nuclear contour irregularity. There is also a smattering of histiocytes with engulfed red cells.

Figure 6.31

The phenotypic profile reveals that the lymphocytes at least focally are CD3+. However, there are a number of cells that are not staining. The infiltrate probably contains more histiocytes.

Figure 6.32

There is a diminution in the expression of CD7. Many of the cells within the panniculus are without any CD7 expression.

Figure 6.33

Of interest, the infiltrate is not convincingly CD4 or CD8 positive. There are a few scattered CD4 or CD8 positive cells; however, the majority of cells within the infiltrate are both CD4 and CD8 negative. Part (a) illustrates CD4 and part (b) depicts CD8.

Figure 6.34

Biopsy shows infiltration of the outer root sheath epithelium by lymphocytes with concomitant perivascular lymphocytic infiltrates. The pattern of migration is largely a passive folliculotropic one.

Figure 6.35

Higher-power magnification reveals infiltration of the adventitial dermis by lymphocytes with focal infiltration of the outer root sheath epithelium by lymphocytes. The pattern is one of epitheliotropism, as opposed to classic follicular interface dermatitis, as one would encounter in underlying collagen vascular disease.

Figure 6.36

Higher-power magnification reveals rather striking lymphoid atypia. Many of the cells have a cerebriform appearance. This patient is best categorized as having a form of pilotropic T cell dyscrasia compatible a with mucin-poor variant of alopecia mucinosa.

Figure 6.37

The CD7 preparation shows a reduction in expression of CD7. A few of the lymphocytes are positive.

Figure 6.38

The biopsy shows infiltration of the follicle by lymphocytes with attendant follicular mucinosis.

Figure 6.39

Higher-power magnification shows mild lymphoid atypia. There is also conspicuous mucin deposition.

Figure 6.40

The infiltrate in the follicle is CD3 dominant (a) and composed primarily of CD4+ T cells (b).

Figure 6.41

The CD7 preparation shows a loss of CD7 expression.

Figure 6.42

Polyclonal molecular profile. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.43

This photomicrograph depicts the classic changes encountered in a spectrum of adnexotropic T cell dyscrasias, namely syringolymphoid hyperplasia with alopecia, syringotropic T cell lymphoma, and alopecia mucinosa, including the so-called mucin-poor variant also falling under the alternative appellation of follicular lymphocytosis and finally pilotropic MF. Specifically, there is migration of lymphocytes into the outer root sheath epithelium with attendant striking follicular hyperkeratosis.

Figure 6.44

A higher-power magnification showing the atypicality of the lymphocytes permeating the outer root sheath epithelium.

Figure 6.45

There is hyperplastic alteration of the straight eccrine duct. The hyperplasia is accompanied by lymphocyte migration around and within the eccrine ductular and glandular epithelium. Virtually identical changes occur in patients with the prelymphomatous dyscrasia of syringolymphoid hyperplasia with alopecia. Unlike this patient, such patients present with isolated patches of alopecia with accompanying anhidrosis.

Figure 6.46

The patient developed the same lymphoepitheliotropic process in the lung, which antedated the skin lesions by a few years.

Figure 6.47

Intermediate-power examination reveals focal infiltration of the outer root sheath epithelium by lymphocytes with accompanying slight spongiosis.

Figure 6.48

Examination under oil reveals an atypical lymphocytic cytomorphology. The cells are predominantly small in size, however they exhibit significant nuclear contour irregularity with cells having a cerebriform appearance.

Figure 6.49

Patchy perivascular and interstitial lymphocytic and histiocytic infiltrate within the panniculus.

Figure 6.50

Higher-power examination reveals a small dominant lymphocytic cell population with slight lymphocytic atypia.

Figure 6.51

Within the dermis there are scattered singly disposed plump histiocytes, some of which manifest erythrocyte phagocytosis.

Figure 6.52

A 6-year-old girl was diagnosed with clonally restricted endogenous epitheliotropic T cell dyscrasia manifesting a CD4+ CD7+ focally CD62L-negative phenotype consistent with pityriasis lichenoides chronica. The molecular studies show a clonal population of T lymphocytes. The dominant T cell populations included one population at 259 bp and another at 186 bp. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.53

A 55-year-old woman with pityriasis lichenoides for over 15 years was diagnosed with cutaneous lymphoid dyscrasia. The molecular studies show that three blocks (A1, B1, and C1) are quite similar and show restricted T cell repertoire with one to four slightly dominant peaks in each multiplex panel. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.54

A 14-year-old girl was diagnosed with pigmented purpuric dermatosis. The molecular studies show an emerging clonal population of T-lymphocytes in a polyclonal background. The molecular study results from both blocks, representing different biopsy sites procured at different time periods, are very similar with respect to each of the pair of panels. Panel A shows minimal PCR products. Panel B does not show any peaks, while panel C shows dominant T cell populations at 298 bp and 306 bp. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.55

A 15-year-old girl with a longstanding history of eczema and now with widespread hypopigmented patches was diagnosed with hypopigmented large plaque parapsoriasis. (a) The molecular studies show, on panel C, a peak at 183 bp. (b) The molecular studies show multiple distinct peaks on blocks A and C, classified as a restricted repertoire. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.56

A 68-year-old man with a history of hypertension and achalasia was diagnosed with idiopathic erythroderma. The molecular studies show oligoclonal peaks on blocks A and C. On panel B, peaks are present at 259 bp and 265 bp. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.57

A 35-year-old man was diagnosed with large plaque parapsoriasis. The molecular studies show, on all three blocks of panel C, peaks at 189 bp. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.58

A 49-year-old woman with an isolated lesion on the left upper arm was diagnosed with large plaque parapsoriasis. TCR-

β

gene rearrangement of whole sections shows that panels A and C have a polyclonal pattern, while LCM (laser capture microdissection) reveals the same panels with monoclonal peaks. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.59

A 73-year-old man with alopecia mucinosa. The molecular studies show a monoclonal peak at 258 bp on panel A, and on panels B and C at 272 bp and 178 bp, respectively. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.60

The patient is a 6-year-old boy with a 1-year history of waxing and waning subcutaneous nodules, who was diagnosed with atypical lymphocytic lobular panniculitis. The biopsy showed a very striking lymphocytic infiltrate with focal loss of CD5 and CD7. The lymphocytes were composed of a mixture of CD4- and CD8-positive cells. The patient felt well. An outside consultant raised diagnostic considerations of subcutaneous anaplastic large cell lymphoma and gamma-delta panniculitis-like T cell lymphoma. The patient was categorized as having atypical lymphocytic lobular panniculitis over one of panniculitis-like T cell lymphoma. The TCR-

β

test shows dominant peaks at 187 bp for panel C and 257 bp for panel B. Two biopsies were obtained over 18 months showing quantitative progression of a constant T cell clonotype to eventuate into a true monoclonal profile. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.61

A 46-year-old man was diagnosed with pigmentary purpura. The TCR-

β

test shows monoclonal peaks at 189 bp for all three biopsies on panel C. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.62

A 36-year-old man with nodules in the right thigh and leg was diagnosed with atypical lymphocytic lobular panniculitis. The molecular studies show similar results for two biopsies. Both of the TCR-

β

results from the two biopsies on panel A show a peak at 254 bp. On panel C, oligoclonal peaks are present at 185 bp and 303 bp. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 6.63

The patient presented with a persistent keratoderma which raised diagnostic consideration of psoriasis and dyshidrotic eczema. A diagnosis was made of a keratoderma-like T cell dyscrasia, although atypical diagnostic features of MF palmaris et plantaris were not seen.

Figure 6.64

The biopsy shows a prominent psoriasiform pattern of epidermal hyperplasia with striking hyperkeratosis. There is a supervening superficial lymphocytic infiltrate which is angiocentric and epitheliotropic. The pattern of keratinization is primarily orthohyperkeratosis with minimal parakeratosis.

Figure 6.65

The granular cell layer is diminished. There is colonization of the basal layer by lymphocytes accompanied by small aggregates of lymphocytes within the mid spinous layer of the epidermis. The morphology captured in this biopsy is reminiscent of pityriasis lichenoides.

Figure 6.66

The cohesive aggregate of lymphocytes and histiocytes in the upper spinous layer of the epidermis mimics a Pautrier’s microabscess, but is different by virtue of the lack of greater lymphoid atypia and the number of admixed histiocytes.

Figure 6.67

There is basilar colonization of the epidermis by lymphocytes defining a pattern that is common in many of the epitheliotropic T cell dyscrasias and which should not be construed as being diagnostic of MF.

Figure 6.68

The extent of the lymphocytic infiltrate is highlighted by the CD3 stain.

Figure 6.69

There is a significant reduction in the extent of immunoreactivity for CD7.

Chapter 7

Figure 7.1

Marginal zone lymphoma/immunocytoma.

Classic clinical morphology of immunocytoma characterized by grouped coalescing erythematous to violaceous papules and plaques.

Figure 7.2

Sclerosing immunocytoma (scleromyxedema-like) mimicking eruptive dermatofibromas.

The patient was a healthy weight lifter who developed multiple indurated pink papules, suggestive of eruptive dermatofibromata. The biopsy showed a pattern of multinodular sclerosis reminiscent of scleromyxedema. Molecular studies revealed a clonally restricted B cell population; the phenotype was a light-chain-restricted plasmacytic infiltrate. A diagnosis of a sclerosing variant plasmacytic marginal zone lymphoma/immunocytoma was made (see molecular gels 7.40 and 7.41).

Figure 7.3

One of the skin nodules demonstrates a massive nodular lymphoid infiltrate, which effaces the dermal architecture.

Figure 7.4

Under 10× objective magnification one can see that the infiltrate is predominated by small monomorphous-appearing mature lymphocytes. Dispersed throughout the lesion are reactive germinal centers, as characterized by nodules containing centroblastic cells with admixed tingible body macrophages.

Figure 7.5

Higher-power magnification reveals the infiltrate to be composed of small mature lymphocytes.

Figure 7.6

A CD3 preparation shows only a smattering of T lymphocytes suggesting that the dominant lymphoid papular is one of B cells.

Figure 7.7

A CD23 preparation highlights the reactive germinal centers and also shows the irregular nature of the dendritic network due to infiltration of the germinal center by small marginal zone lymphocytes.

Figure 7.8

The patient presented initially with an orbital mass. There is extensive infiltration of the orbital soft tissue by a diffuse nodular lymphocytic infiltrate.

Figure 7.9

The infiltrate is predominated by small mature lymphocytes in the 7–9 μm size range.

Figure 7.10

Under 40× one can see that the dominant cytomorphology is a small lymphocyte; however, there are some elements of cytomorphologic heterogeneity. Specifically, some of the cells have a small cleaved appearance, while other cells appear more plasmacytoid, demonstrating a closely condensed heterochromatin and a peripheral nuclear disposition. A few plasma cells are also noted.

Figure 7.11

Under 100× objective magnification, the heterogeneous nature of the cytomorphology is further exemplified. Specifically, there are cells with a small lymphoplasmacytoid appearance, as characterized by a peripheral condensation of chromatin to the nuclear membranes with conspicuous centrally located nucleoli with variable eccentric disposition of the nucleus and somewhat amphophilic cytoplasm. In addition, there are small cleaved lymphocytes with angulated and irregularly contoured nuclear profiles. These cells are roughly the same size as the adjacent red cells (i.e., in the 7–9 μm size range).

Figure 7.12

Immunohistochemical stains reveal that the infiltrate is predominated by CD20-positive B lymphocyte (20×).

Figure 7.13

A CD23 preparation highlights germinal-center-like foci, although it shows extensive lytic alteration of the germinal centers by virtue of infiltration of the germinal-center-like foci by small lymphocytes. Additionally, the small lymphocytes are noticeably CD23 negative.

Figure 7.14

Low-power examination under 2× objective magnification reveals a dense nodular infiltrate that focally effaces the dermal architecture.

Figure 7.15

Higher-power magnification shows that the infiltrate is predominated by small mature lymphocytes.

Figure 7.16

Higher-power magnification shows that the dominant infiltrate is one of small mature lymphocytes with hyperchromasia and slight nuclear angulation. There are also scattered large centroblastic cells with vesicular chromatin and multiple chromocenters.

Figure 7.17

A CD21 preparation highlights reactive germinal centers (20× objective magnification). Nevertheless, there is some irregularity in the dendritic staining pattern with significant areas of dendritic cell lysis due to infiltration of the germinal center-like foci by neoplastic small lymphocytes.

Figure 7.18

There is positive staining of B lymphocytes with the pan T cell marker CD43.

Figure 7.19

Higher-power magnification shows intense staining of the cells for CD20.

Figure 7.20

In situ

hybridization studies do not reveal any of the staining of the infiltrate for lambda (a), although there is extensive staining for kappa (b).

Figure 7.21

The biopsy demonstrates a striking multinodular lymphocytic infiltrate involving the entire sampled thickness of the dermis with a narrow grenz zone of uninvolved dermis separating the infiltrate from the overlying epidermis.

Figure 7.22

Higher-power magnification reveals an infiltrate comprising small- and intermediate-sized lymphocytes.

Figure 7.23

The CD21 preparation highlights a dendritic antigen presenting cell network within the reactive germinal centers. (a) The findings are in contradistinction to those encountered in neoplastic germinal centers, whereby there is significant dendritic cell lysis due to penetration of the germinal center by neoplastic small lymphocytes (b).

Figure 7.24

A CD10 preparation shows weak staining of the germinal center-like foci (20× objective magnification.)

Figure 7.25

A bcl-2 preparation shows positive staining amid the centroblastic and immunoblastic cells of the germinal center-like foci. The two possibilities are those of infiltration of the germinal center by neoplastic marginal zone lymphoma cells versus incipient neoplastic transformation of follicles. It is well established that composite lymphomas, combining overlap features of marginal zone lymphoma and follicular lymphoma, may exist.

Figure 7.26

The biopsy shows a band-like and nodular lymphocytic infiltrate lying in intimate apposition involving the superficial dermis. While the pattern might be more reminiscent of a T cell lymphoproliferative process, higher-power magnification reveals an atypical plasmacytic infiltrate, as depicted in Figure 7.27.

Figure 7.27

Higher-power magnification reveals significant plasma cell dysplasia, including intranuclear inclusions compatible with Dutcher body formation.

Figure 7.28

Higher-power magnification reveals significant plasma cell atypia. The cells exhibit binucleation and trinucleation.

Figure 7.29

The biopsy shows a superficial and deep nodular infiltrate, which assumes a heavier pattern of infiltration as the base is approached.

Figure 7.30

The infiltrate has a heterogeneous composition comprising small, mature lymphocytes and an admixture of plasma cells.

Figure 7.31

The biopsy shows a dense lymphocytic and plasmacytic infiltrate lying in close apposition to the eccrine coil. Frank permeation of the eccrine duct and glands by B lymphocytes would define an important morphologic clue pointing toward lymphoma.

Figure 7.32

The infiltrate also shows accentuation around the hair follicle.

Figure 7.33

The plasma cells appear atypical. Some appear binucleated and there is variation in nuclear size and shape. Instead of the classic clockface chromatin encountered in the mature plasma cell, the cells have a finely dispersed heterochromatin.

Figure 7.34

In situ

hybridization studies for (a)

κ

and (b)

λ

reveal a striking dominance of

κ

over

λ

. The ratio is very high.

Figure 7.35

The biopsy shows a striking pandermal nodular infiltrate with extension into the subcutaneous fat. The infiltrate manifests accentuation around adnexal structures.

Figure 7.36

Higher-power magnification reveals a mixture of small mature lymphocytes and atypical-appearing plasma cells. The small lymphoid populace includes cells with nuclear irregularity and a finely dispersed heterochromatin. The plasma cells have less than mature-appearing chromatin.

Figure 7.37

The phenotypic profile reveals a dominance of CD20 cells (b) over those of the CD3 subset (a). The ratio is high.

Figure 7.38

The CD23 stain highlights reactive germinal centers.

Figure 7.39

The

in situ

hybridization studies for kappa and lambda reveal an overwhelming dominance of kappa-staining cells over those of the lambda subset. The ratio is high.

Figure 7.40

The molecular studies show identical monoclonal B cell populations with polyclonal background on the separate biopsies. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 7.41

The molecular studies show oligoclonal peaks with polyclonal background on the three different samples. On all three biopsies, peaks are present at 94 bp and 102 bp. The patient has a sclerosing variant of marginal zone lymphoma. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 7.42

IgH gene rearrangement shows monoclonal peaks at 258 bp with minimal to no polyclonal background on two separate biopsies from this one patient. (

Source

: Dr. Carl Morrison, Roswall Park Cancer Institute. Reproduced with permission.)

Figure 7.43

Another biopsy shows a dominant B cell population at 289 bp.

Figure 7.44

The typical changes of the hyaline vascular variant are seen. The case is very unusual, not only in the context of representing subcutaneous Castleman disease, but dendritic cell sarcoma arose in this background of atypical lymphoproliferative lesion. (

Source

: Dr. Saul Suster. Reproduced with permission.)

Figure 7.45

A higher-power magnification shows the atrophic nature of the germinal center. Most of the germinal center comprises small lymphocytes. Only occasional larger cleaved lymphocytes and/or centroblasts are seen. The vessel permeating the germinal center has a hyalinized appearance and defines a conspicuous component of this diminutive germinal center.

Figure 7.46

The patient also had areas of extensive plasma cell infiltration amid atrophic germinal centers, hence defining a mixed variant of Castleman disease.

Figure 7.47

Low-power magnification shows an extensive nodular lymphocytic infiltrate that extends all the way to the base of the biopsy. There is a lack of dermal involvement superficially. 

Figure 7.48

Higher magnification shows the obscuring nature of the lymphocytic infiltrate and its composition being that of a monomorphic appearing larger lymphoid cell with a finely dispersed chromatin and relatively small lightly eosinophilic nucleoli. The cytoplasms are rather abundant and grayish in quality. There are a few smaller lymphocytes that are in the 7–9 μm size range, with a closely condensed chromatin. In contrast, the dominant large cell populace is in the 15 μm size range. Note the paucity of other inflammatory cell elements. 

Figure 7.49

This oil emersion photograph shows the quality of the blastic transformed neoplastic marginal zone juxtaposed to the residuum of neoplastic small cell lymphocytic infiltration. The larger cell populace has a very vesicular clear chromatin. Nucleoli are present but not unusually conspicuous, showing some propensity to lie in apposition to the nuclear membranes. The shapes are predominantly oval and somewhat angulated.

Figure 7.50

At 400× magnification, the neoplastic B cells are extensively CD20 positive. A similar staining pattern is noted for CD79a.

Figure 7.51

There is extensive immunoreactivity of the neoplastic cells for bcl-2. 

Figure 7.52

The neoplastic B cells express IgG although without any staining for IgM. 

Figure 7.53

There is a subset of neoplastic large cells that expresses PD-1. 

Figure 7.54

The neoplastic B cells exhibit kappa light chain restriction. 

Figure 7.55

In contrast, there is no staining of the neoplastic cells for lambda. 

Figure 7.56

Many of the neoplastic cells exhibit MUM1 positivity. 

Figure 7.57

This case of blastic marginal zone lymphoma shows a chromosome 7q deletion. Visualized is the enumeration probe for chromosome 7 showing two discrete green signals. However the red label for chromosome 7q is not visualized, indicative of a chromosome 7q deletion, a characteristic cytogenetic abnormality in the setting of blastic marginal zone lymphoma.

Figure 7.58

The red-brown quality of the lesions along with their symmetry is well exemplified in this photograph.

Figure 7.59

The lower power of this biopsy shows a nodular noneffacing lymphocytic infiltrate.

Figure 7.60

The germinal centers are atrophic and appear hypervascular.

Figure 7.61

The atrophic germinal centers are surrounded by plasma cells. Illustrated is kappa.

Figure 7.62

There is clearly a restriction of lambda as revealed by the extent of positivity of the infiltrate for lambda.

Chapter 8

Figure 8.1

There is a striking superficial and deep nodular lymphocytic infiltrate. The lesion acquires a greater density of infiltration toward the tissue base with focal permeation of the fat by lymphocytes.

Figure 8.2

There is extensive infiltration of the interstices of the fat lobule by lymphocytes, a finding that may be an important architectural clue to the diagnosis of lymphoma.

Figure 8.3

Under higher-power magnification, one can see an arrangement of lymphocytes that recapitulates the germinal center by virtue of a central zone comprising a mixture of cleaved centrocytes and larger centroblasts with a peripheral concentric rim of small mantle-cell-like lymphocytes.

Figure 8.4

Higher-power magnification reveals that the dominant composition of the germinal center comprises small cleaved lymphocytes with only a minor population of immunoblasts and centroblasts (small cell dominant grade I).

Figure 8.5

Under oil immersion (1000× magnification) the small cleaved morphology of the atypical lymphocytes is better appreciated.

Figure 8.6

The majority of the lymphocytes express CD20.

Figure 8.7

A CD10 preparation highlights the germinal-center-like foci.

Figure 8.8

A CD23 preparation highlights the germinal-center-like foci. There is positive staining of the dendritic cells, but with irregularity in the dendritic network, including zones of dendritic cell lysis, the apparent sequela of neoplastic lymphocyte infiltration.

Figure 8.9

A bcl-2 preparation decorates the germinal-center-like foci.

Figure 8.10

A CD21 stain shows significant dendritic cell lysis recapitulating the morphology captured in Figure 8.8.

Figure 8.11

There is a prominent pandermal diffuse and nodular lymphocytic infiltrate that extends into the subcutaneous fat.

Figure 8.12

One can appreciate the follicle-like nature of this process by virtue of the presence of discrete nodules with centroblastic cells surrounded by a mantle-like rim of small mature lymphocytes.

Figure 8.13

Higher-power magnification shows that the composition of the nodule is one comprising atypical centroblastic cells along with smaller centrocytic cells. The larger cell elements show significant cellular atypia, characterized by nuclear contour irregularity and multiple irregular nucleoli. There is also significant mitotic activity. The differential diagnosis of this nodule is one of follicular lymphoma versus an activated germinal center (mixed/grade II).

Figure 8.14

This is a nodule showing a similar composition dominated by pleomorphic large centroblastic elements (large cell dominant/grade III).

Figure 8.15

As these forms of lymphoma usually arise in a background of reactive lymphoid hyperplasia, CD23 and CD21 stains are useful adjuncts to highlight reactive germinal centers. There is a dendritic staining pattern within a germinal center focus likely representing a reactive follicle.

Figure 8.16

A CD23 preparation highlights a reactive germinal center. In contrast, the neoplastic follicles show either irregularity of staining with zones of dendritic cell lysis or complete absence of CD23 staining.

Figure 8.17

Small reactive B lymphocytes express CD79a; however, the germinal center foci are largely devoid of expression, implying a CD79a deletion.

Figure 8.18

In contrast, the CD20 preparation shows extensive decoration of the germinal center foci. Further corroborative evidence of the neoplastic nature of this follicular structure is the virtual absence of CD10 immunoreactivity amid the germinal-center-like foci.

Figure 8.19

Complete absence of CD10 expression in the germinal-center-like foci reflects a CD10 deletion. A lack of CD10 expression by cells that express bcl-6 is characteristic of primary cutaneous follicle center lymphoma and is an important diagnostic discriminator from nodal follicular lymphoma secondarily involving the skin.

Figure 8.20

There is a striking deep-seated infiltrate with extension into the subcutis.

Figure 8.21

A dominant component of the infiltrate is in apposition to the eccrine coil. Involvement of the adventitial dermis does not define a discriminating feature separating marginal zone lymphoma from follicular lymphoma and vice versa.

Figure 8.22

The infiltrate extends deep, abutting on skeletal muscle.

Figure 8.23

The infiltrate is composed of a mixture of small cleaved and larger atypical cells without any interposed histiocytes.

Figure 8.24

Phenotypic studies show a dominance of CD20-positive B lymphocytes (a) over those of the CD3 subset (b). Normally reactive infiltrates are of T cell lineage; hence, any dominance of B cells over T cells is abnormal and a ratio of B to T in excess of 3:1 would be suggestive of B cell lymphoma.

Figure 8.25

While the cells are bcl-6 positive, there is no expression of CD10. Illustrated is CD10.

Figure 8.26

The cells are bcl-6 positive.

Figure 8.27

The CD23 highlights germinal-center-like foci; however, unlike a reactive germinal center, there are significant zones of dendritic cell lysis.

Figure 8.28

The germinal-center-like nodular foci are largely CD21 negative with only focal staining of the residual dendritic network. The failure for a structure resembling a germinal center to express CD21 is suggestive of lymphoma.

Figure 8.29

The biopsy reveals a nodular infiltrate localized to the subcutaneous fat. The nodules resemble germinal centers; however, they are permeated by lymphocytes and focally the borders become ill defined as the infiltrate assumes a more diffuse pattern.

Figure 8.30

Higher-power magnification reveals a composition of small and large lymphocytes without any interposed histiocytes. The smaller cells are centrocytes, while the larger cells have a centroblastic and immunoblastic morphology. The centroblasts typically have peripherally disposed nucleoli lying in apposition to the nuclear membrane. This particular morphology is well exemplified in (b).

Figure 8.31

The nodular foci are bcl-6 positive, indicating that the cells are of follicular origin.

Figure 8.32

Although the cells are bcl-6 positive, they fail to show immunoreactivity with CD10.

Figure 8.33

Unlike classic nodal follicular lymphoma, the cells are bcl-2 negative; note the adjacent rim of small mature bcl-2-positive lymphocytes. In any reactive T-cell component, bcl-2 expression will be observed.

Figure 8.34

There is a predominance of CD20-positive lymphocytes over those of the CD3 subset. In reactive infiltrates, almost invariably there is a dominance of (a) CD3 over (b) CD20. Seeing a predominance of CD20 over CD3 is an important point suggesting a diagnosis of B cell lymphoma.

Figure 8.35

The cytogenetic profile shows a t(14;18)(q32;q21),which is mainly associated with primary nodal follicular lymphoma. This translocation is seen in only 30 to 40% of primary cutaneous follicle center lymphomas.

Figure 8.36

Giemsa trypsin G (GTG) banded karyotype obtained from a lymph node sample of a patient showing 46,XY,add(1)(p36.3),add(1)(p36.3),add(6)(q?23),del(9)(p22),t(14;18) (q32;q21.3) karyotype (abnormal chromosomes marked by arrows). (b) Interphase FISH hybridized with

IGH

(Spectrum Green)

-bcl-2

(Spectrum Orange) dual color dual fusion probes (Abbott Molecular Inc., Des Plaines, IL); fusion signals indicating

IGH-bcl-2

gene rearrangements. (c) Metaphase FISH hybridized with

IGH

(Spectrum Green

)-bcl-2

(Spectrum Orange) dual color dual fusion probes; fusion signals on der(14) and der(18) (white arrows) indicating a t(14;18)(q32;q21.3) translocation. This characteristic translocation found in nodal follicular lymphomas is identified in 30% of primary cutaneous follicle center lymphomas.

Chapter 9

Figure 9.1

Primary cutaneous large cell lymphoma, leg type.

The patient developed violaceous plaques on the lower extremities. A biopsy was performed and held to be compatible with a diagnosis of primary cutaneous large cell lymphoma, leg type.

Figure 9.2

Diffuse large B cell lymphoma (follicle center type (group 2)).

The patient is a 70-year-old man who developed a progressively enlarging fungating mass on the upper back over a 4-year period. He was otherwise well. The biopsy was diagnostic of a bcl-2-negative, bcl-6-positive diffuse large cell lymphoma consistent with a diffuse large cell variant of primary cutaneous follicle center lymphoma. (

Source

: Dr. Kelly Gallina, The Ohio State University. Reproduced with permission.)

Figure 9.3

Primary cutaneous B cell lymphoblastic lymphoma

. The child presented at 6 weeks of age with a large infiltrative violaceous plaque involving the eye. The biopsy was compatible with primary cutaneous B cell lymphoblastic lymphoma. (

Source

: Dr. Samir Kahwash, Children's Hospital, Columbus, OH. Reproduced with permission.)