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Cutaneous Lymphoid

Hyperplasia, Cutaneous T-CellLymphoma, Other Malignant

Lymphomas, and AlliedDiseases

Rick Lin, DO, MPH

March 18, 2003

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Cutaneous Lymphoid Hyperplasia

Collection of lymphocytes with otherinflammatory cells on the skin

Maybe monoclonal or mixed with both T orB cells

Caused by unknown stimuli

Medications, infections,

insect bites

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Cutaneous Lymphoid Hyperplasia

AKA Pseudolymphoma

May progress to lymphoma

Immunosuppression may aggravate the

infiltrate and may regress with

immunosuppression is removed

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Cutaneous B-Cell Lymphoid

Hyperplasias Knowns as Speigler-Fendt sarcoid

Caused by Borrelia, infections, herpes zostersscars, tatoo, drugs

Appears as discrete firm of doughy cutaneouspapules or nodules

Most lesions are asymptomatic, treatment notrequired

If caused by medication, medication should beremoved

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Cutaneous T-Cell Lymphoid

Hyperplasias Maybe idiopathic

Aka actinic reticuloid and chronic actinic

dermatitis

Patient resembles mycosis fungoides

Histologically, dermal infiltrate that is

band-like with no grenz zone.

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Cutaneous lymphoid hyperplasia

Pseudolymphoma has to be distinguished fromcutaneous lymphomas by the combination ofclinicopathological correlation, histochemical

studies, and, in selected cases, generearrangement studies

T cell lymhoma can be usually distinguishedfrom T cell pseudolymphoma by the presence of

prominent epidermotropism, large and atypicallymphocytes, and T cell gene rearrangementsup to 90%

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Cutaneous lymphoid hyperplasia

The lack of acanthosis, "bottom-heavy"

infiltrates, light-chain expression of monotypical

B-cells, and immunoglobulin generearrangements (75%) provide strong evidence

for the diagnosis of B-cell lymphoma

A careful monitoring of these patients for the

development of lymphoma is necessary

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Coalescingerythematous

follicular papules andraspberry-like noduleson the right shoulder.

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Histological examinationof the skin

The microscopic

examinations revealed

dense and diffuse

infiltrates of cytologically

benign-appearing

lymphocytes andscattered histiocytes in

the upper and mid dermis

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Immunohistochemicalexamination of skin.

Antibody againstCD3+ (T-lymphocytes).

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Cutaneous T Cell Lymphomas

Primary Cutaneous T-Cell LymphomasNot synonymous with MF

Up to 30% of primary CTCLs are not MF

Primary Cutaneous T-Cell Lymphomas

other than Mycosis Fungoides

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Primary Cutaneous T-Cell

Lymphomas Primary Cutaneous T-Cell Lymphomas

Mycosis Fungoides

Pagetoid Reticulosis

Sezary Syndrome

Granulomatous Slack Skin

Lymphomatoid papulosis

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Mycosis Fungoides

Malignancy of T-lymphocytes, almost always MEMORYT-CELL

Black>white

M:F = 2:1 Race: MF is more common in black than in white

patients (incidence ratio 1.6).

Sex: MF occurs more frequently in men than in women(male-to-female ratio of 2:1).

Age: The most common age at presentation is 50 years;however, MF also can be diagnosed in children andadolescents with apparently similar outcomes.

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Mycosis Fungoides

Patch Stage premycotic, severe pruritis.

Plaque Stage infiltrated plaque

Tumore stagewhen de novo, called d

emblee form

Erythroderma Rare

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MF Staging

TNMB system on skin (T) node (N),viscera (M), and blood (B)

T1 Skin involvement 10%

T3 Tumor T4 Erythroderma

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MF Staging

N0 normal nodes

N1 palpable but not pathologically MF

N2 not palpable but pathologically MF N3 clinically and pathologically involved

M0 B0 - Viscera and blood not involved M1 B1 - Viscera and blood involved

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MF Staging

Stage IA T1, N0, M0 8-9% progress

Stage IB T2, N0, M0 11-16 years surv

Stage IIA T1-2, N1, M0 7.7 years Stage IIB T3, N0-1, M0 3-8 years surv

Stage IIIA T4, N0, M0 1.8-3.7 years

Stage IIIB T4, N1, M0 1.8-3.7 years

Stage IVA T1-4, N2-3, M0

Stage IVB T1-4, N0-3, M1

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Lymph nodes in MF

Extracutaneous involvement is more clinically

evident as the stage and extent of MF increases

Peripheral lymphadenopathy is the mostfrequent site of extracutaneous involvement in

MF

Evaluate palpable lymphadenopathy by

obtaining a biopsy because the result influences

the patients stage, prognosis, and treatment.

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MF Workup

CBC to review the buffy coat smear for Lymphnodes

CMP

Liver Function to include LDH (aggressive) andtransaminase (liver involvement) values

CXR

If lymph nodes are palpable CT to access abdominal and pelvic nodes Lymph node biopsy

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Histologic Findings

The criteria for diagnosis include the following:

A bandlike upper dermal infiltrate of lymphocytes andother inflammatory cells, with no grenz zone, is present.

Epidermotropism of mononuclear cells occurs. When a clear halo surrounds an intraepidermal

mononuclear cell singly or in clumps, this is called aPautrier microabscess. Its presence is suggestive of MF,but it is not necessary for diagnosis.

Little spongiosis of the epidermis is found. Lymphocytes have nuclei that are hyperchromatic and

convoluted or cerebriform.

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Pagetoid Reticulosis

Localized epidermotropic reticulosis

Woringer-Kolopp disease

Acral mycoses fungoides

Mycosis fungoides palmaris et plantaris

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Pagetoid Reticulosis

0.6% of all MF cases

Woringer-Kolopp variant: solitary lesion

Ketron-Goodman variant: multiple lesions Long durantion without progression to frank

lymphoma is the clincal hallmark of Woringer-

Kolopp

Local excision and radiation therapy maybe

curative.

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Scan power view. Hyperkeratosis is associated with

papillomatosis

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Medium power view. Keratinocyte enlargement is seen, and this can occur

whenever there is an abnormal cell population in the lower epidermis. Clusters

of dark mononuclear cells are in all levels of the epidermis.

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High power view. It would be difficult to distinguish between abnormal T

cells and small, dark, lymphocytoid melanocytes in this field.

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Scattered

plaque-likelesions on

both lowerextremities.

Ketron-

Goodman

disease

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Band-like infiltration of lymphoid cells in lower epidermis and upper dermis.

Intraepidermal infiltrate were medium- to large-sized atypical cells. Lymphoid

cells infiltrating upper dermis revealed no overt atypicality.

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Sezary Syndrome

Leukemic phase of mycosis fungoides

Generalized erythroderma, superficial

lymphadenopathy, atypical cells in circulatingblood

Erythroderma from onset with leonine facies,

eyelid edema, ectropion, alopecia, palm and

sole hyperkeratosis

Pruritis, burning, chill and profuse sweating

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Prognosis

Difficult to treat

Median survival is 3 years

Low dose methotrexate has reasonableresponse rate of 50%

Photophoresis

Retinoid, interferon alfa, lowdosechlorabucil, prednisone, systemic chemo

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Granulomatous Slack Skin

Rare variant of CTCL

Middle-age adult and gradually progress

Erythematous atrophic pendulous

redundant plaque

Multinucleated giant cells replaces fat

lobules histologically.

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Lymphomatoid Papulosis

LyP has a chronic indolent course in most patients;

estimates indicate that as many as 10-20% of LyPpatients have a history of associated malignantlymphoma (ALCL, HD, or mycosis fungoides [MF]) priorto, concurrent with, or subsequent to the diagnosis ofLyP.

Race: Black persons may be less affected than otherracial groups.

Sex: No consistent sex predominance is found instudies.

Age: LyP may develop at any age, usually in the third tofourth decade

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Presentation

Primary lesion: Each erythematous papule evolves into ared-brown, often hemorrhagic, papulovesicular orpapulopustular lesion over days to weeks.

Some lesions develop a necrotic eschar before healingspontaneously. Occasionally, noduloulcerative lesionsmay be present

Each papule heals within 2-8 weeks, leaving ahypopigmented or hyperpigmented depressed ovalvarioliform scar.

Large nodules and plaques may take months to resolve. Distribution: Characteristically, lesions appear on the

trunk and extremities, although the palms and/or soles,face, scalp, and anogenital area also may be involved.

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Lymphomatoid Papulosis

Type A: Characterized by large (25-40 mm) CD30+atypical cells with polymorphic convoluted nuclei and aminimum of 1 prominent nucleolus. These large cells

resemble Reed-Sternberg cells when binucleate. TypeA LyP is the most common histologic variant.

Type B: Characterized by smaller (8-15 mm) atypicalcells with hyperchromatic cerebriform nucleiresembling the atypical lymphocytes in MF. CD30+

large cells are rare, but epidermotropism is morecommon in this variant.

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Lymphomatoid Papulosis

Type C (diffuse large cell type):

Characterized by sheets of CD30+

anaplastic large cells

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Treatment of LyP

mid-to-high potency topical steroids to hasten resolution.

Low-dose weekly methotrexate is a safe and effectivetreatment for suppressing LyP; however, the diseaserecurs within 1-2 weeks after ending medication.

Oral psoralen plus UV-A phototherapy (PUVA) alsoeffectively treats and suppresses the disease.

carmustine, topical nitrogen mustard, intralesionalinterferon, low-dose cyclophosphamide, chlorambucil,and dapsone help disease suppression.

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Primary CTCL other than Mycosis

Fungoides CD30-positive cutaneous T-Cell Lymphoma Secondary Cutaneous CD30 positive large-cell

lymphoma

Non-MF CD30-negative cutaneous large T-celllymphoma Non-MF CD30-negative cutaneous pleomorphic

small or medium sized cell lymphoma

Subcutaneous (Panniculitis-Like) T-CellLymphoma

Nasal/Nasal Type T/NK Cell Lymphoma

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CD30-positive cutaneous T-Cell

Lymphoma Present as solitary or localized skin

lesions with tendency to ulcerate and have

spontaneous regression Rare in children, occur more frequesntly in

males

5 year survival rate 90% Highly responsive to ratiotherapy

Lesions can be surgically excised

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Secondary CD30-positive

cutaneous T-Cell Lymphoma CD30 Positive CTCL arise from MF

Poor prognosis

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Non-MF CD 30 Negative

Cutaneous Large T-Cell lymphoma Solitary or generalized plaque or tumor of

short duration, no patch stage

Prognosis is poor, 15% 5 year survival Malignant cells are pleomorphic large or

medium cell types

Non MF CD 30 Negati e

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Non-MF CD 30 Negative

Cutaneous Small or Medium Size

Cell T-Cell lymphoma

Differentiate from large-cell type by having

less than 30% large pleomorphic celll. Similar to large type clinically

Prognosis is better than large cell type.

50% 5 year survival. Radiation tx, interferon alfa, or

cyclophosphamide are effective

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Subcutaneous (Panniculitis-Like) T-

Cell Lymphoma Clinically presents with subcutaneous

nodules

Usually on lower extremities Frequently diagnosed as having erythema

nodosum or other forms of panniculitis

Poor prognosis

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A, Marked edema of right calf at time of presentation. B, Erythematous noduleswith associated vascular ectasia on abdominal wall.

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High-power view of infiltrate showing random atypical

lymphocytes

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Cutaneous B-Cell Lymphoma

Primary Cutaneous Follicular Center Cell

Lymphoma

Primary Cutaneous Immunocytoma Intravascluar Large B-Cell Lymphoma

Plasmacytoma (Multiple Myeoloma)

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Primary Cutaneous Follicular

Center Cell Lymphoma AKA B-Cell lymphoma of follicular center cell

origin

AKA Reticulohistiocytoma of the dorsum Multiple papules and nodules in one anatomic

region.

2/3 of case on the trunk, 1/5 on the head and

neck

15% on the leg

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Primary Cutaneous Follicular

Center Cell Lymphoma M:F = 2:1

Prognosis: Head and neck 100% 5 yr surv.

Leg lesion of people over 70, 50% 5 yrsurv.

Stains with B-Cell marker CD 20,

monotypic for immunoglobulin productionof kappa or lambda chain, not both

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Primary Cutaneous Immunocytoma

AKA Marginal Zone B-Cell Lymphoma

AKA MALT Type Lymphoma

SubQ nodule or tumor primaroily of theextremities or trunk

CD79, CD 20, and bcl-2 positive

5 years survival near 100%

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Plasmacytoma

Multiple Myeloma Spectrum of solitary plasmacytoma to

multiple plasmacytoma to multiple

myeloma. Neoplasm of B lymphcytes

Multiple myeloma is most common

characterized by lytic bone lesions andinfiltration of bone marry by plasma cells

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Plasmacytoma

Multiple Myeloma Cutaneous plasmacytomas seen most

commonly a secondary lesion in thesetting of primary myeloma. Prognosis ispoor.

When bone film and bone biopsy arenormal but cutaneous lesions present,

these are primary cutaneousplasmacytoma. Excellent prognosis.

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Densemononuclear

infiltrate within

entire dermis.

This represent

a primary

cutaneous

plasmacytoma

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Neoplastic plasma cells, some with atypical

features, are visible J Am Acad Dermatol 2000;43:962-5.)

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Plasmacytoma

Multiple Myeloma

Numerous nonspecific skin lesions occurs

in patient with multiple myeloma.

AmyloidosisCutaneous vasculitis

alopecia

RaynaudsPyoderma gangrenosum

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Hodgkins Disease

Vast majority of cutaneous Hodgkins

disease report are type A lymphomatoid

papulosis with Reed-Sternberg Difficult to prove cutaneous disease

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Malignant Histiocytosis

Rare, fatal occur in men in second to

fourth decade of life

Solitary lesion or wide spread papuleoccur in 10% of cases

Onset of acute fever, hepatosplenomegly,

and painful lymphadenopathy

Malignant histiocytosis Extensive

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Malignant histiocytosis. Extensive

superior orbital involvement in a

young adult male.

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Extensive erythrophgocytosis by

histiocyte in marrow, liver, spleen

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Leukemia Cutis

30% of Leukemia patient will have leukemiacutis

Vast majority of derm manifestation are from

AML Morphology: 60% multiple papules and nodules,

26% of infiltrated plaques

Subtypes and variants:

Granulocytic SarcomaHairy-cell Leukemia

Nonspecific Condition associated with Leukemia

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Cutaneous Myelofibrosis

Overproduction and premature death of atypical

megakaryocytes in bone marrow

Inrease in platelet-derived growth factor Extramedullary hematopoesis is the hallmark

Blast cells escape marrow and enter circulation

and form tumor

Cutaneous EMH reported in 20 cases

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Hypereosinophilic Syndrome

Icrease Eos with more than 1500 eos per

cubit millimeter for 6 month or more.

Cardiac disease most frequentcomplication

90% patient are men between 20 to 50

Angioedema and urticaria lesions mostcommon. Sometimes papules.

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A i i bl ti T C ll

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Angioimmunoblastic T-Cell

Lymphoma

AKA Angioimmunoblastic T-CellLymphoma

Uncommon, affect middle age and elderly Unspecific skin finding (pruritis, skin rash)

Unspecific histology finding (patchyperivascular dermal infiltrate)

Lymph node biopsy required for diagnosis

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Polycythemia Vera

Increase hermatocrite to 55% to 80%

Associated with aquagenic pruritis in 50%

of the patients. Elevation of blood and skin histamine

Tx control of pruritis by antihistamin or

PUVA. Referral to HemOnc