Cutaneous Lymphoid Hyperplasia, Cutaneous T-Cell Lymphoma, Other Malignant Lymphomas, and Allied Diseases

Rick Lin, DO, MPHMarch 18, 2003

Cutaneous Lymphoid Hyperplasia

Collection of lymphocytes with other inflammatory cells on the skin

Maybe monoclonal or mixed with both T or B cells

Caused by unknown stimuliMedications, infections, insect bites

Cutaneous Lymphoid Hyperplasia

AKA Pseudolymphoma May progress to lymphoma Immunosuppression may aggravate the

infiltrate and may regress with immunosuppression is removed

Cutaneous B-Cell Lymphoid Hyperplasias Knowns as Speigler-Fendt sarcoid Caused by Borrelia, infections, herpes zosters

scars, tatoo, drugs Appears as discrete firm of doughy cutaneous

papules or nodules Most lesions are asymptomatic, treatment not

required If caused by medication, medication should be

removed

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.

Cutaneous lymphoid hyperplasia

Pseudolymphoma has to be distinguished from cutaneous lymphomas by the combination of clinicopathological correlation, histochemical studies, and, in selected cases, gene rearrangement studies

T cell lymhoma can be usually distinguished from T cell pseudolymphoma by the presence of prominent epidermotropism, large and atypical lymphocytes, and T cell gene rearrangements up to 90%

Cutaneous lymphoid hyperplasia

The lack of acanthosis, "bottom-heavy" infiltrates, light-chain expression of monotypical B-cells, and immunoglobulin gene rearrangements (75%) provide strong evidence for the diagnosis of B-cell lymphoma

A careful monitoring of these patients for the development of lymphoma is necessary

Coalescing erythematous follicular papules and raspberry-like nodules on the right shoulder.

Histological examination of the skin

The microscopic examinations revealed dense and diffuse infiltrates of cytologically benign-appearing lymphocytes and scattered histiocytes in the upper and mid dermis

Immunohistochemical examination of skin. Antibody against CD3+ (T-lymphocytes).

Cutaneous T Cell Lymphomas

Primary Cutaneous T-Cell LymphomasNot synonymous with MFUp to 30% of primary CTCLs are not MF

Primary Cutaneous T-Cell Lymphomas other than Mycosis Fungoides

Primary Cutaneous T-Cell Lymphomas Primary Cutaneous T-Cell Lymphomas

Mycosis FungoidesPagetoid ReticulosisSezary SyndromeGranulomatous Slack SkinLymphomatoid papulosis

Mycosis Fungoides

Malignancy of T-lymphocytes, almost always MEMORY T-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 and adolescents with apparently similar outcomes.

Mycosis Fungoides

Patch Stage – premycotic, severe pruritis. Plaque Stage – infiltrated plaque Tumore stage – when de novo, called d’

emblee form Erythroderma – Rare

MF Staging

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

T1 – Skin involvement <10% T2 – Skin involvement >10% T3 – Tumor T4 – Erythroderma

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

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

Lymph nodes in MF

Extracutaneous involvement is more clinically evident as the stage and extent of MF increases

Peripheral lymphadenopathy is the most frequent site of extracutaneous involvement in MF

Evaluate palpable lymphadenopathy by obtaining a biopsy because the result influences the patient’s stage, prognosis, and treatment.

MF Workup

CBC – to review the buffy coat smear for Lymph nodes

CMP Liver Function to include LDH (aggressive) and

transaminase (liver involvement) values CXR If lymph nodes are palpable

CT to access abdominal and pelvic nodes Lymph node biopsy

Histologic Findings

The criteria for diagnosis include the following: A bandlike upper dermal infiltrate of lymphocytes and

other 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 a Pautrier 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.

Pagetoid Reticulosis

Localized epidermotropic reticulosis Woringer-Kolopp disease Acral mycoses fungoides Mycosis fungoides palmaris et plantaris

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.

Scan power view. Hyperkeratosis is associated with

papillomatosis

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.

High power view. It would be difficult to distinguish between abnormal T cells and small, dark, lymphocytoid melanocytes in this field.

Scattered plaque-like lesions on both lower extremities.Ketron-Goodman disease

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.

Sezary Syndrome

Leukemic phase of mycosis fungoides Generalized erythroderma, superficial

lymphadenopathy, atypical cells in circulating blood

Erythroderma from onset with leonine facies, eyelid edema, ectropion, alopecia, palm and sole hyperkeratosis

Pruritis, burning, chill and profuse sweating

Prognosis

Difficult to treat Median survival is 3 years Low dose methotrexate has reasonable

response rate of 50% Photophoresis Retinoid, interferon alfa, lowdose

chlorabucil, prednisone, systemic chemo

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.

Lymphomatoid Papulosis

LyP has a chronic indolent course in most patients; estimates indicate that as many as 10-20% of LyP

patients have a history of associated malignant lymphoma (ALCL, HD, or mycosis fungoides [MF]) prior to, concurrent with, or subsequent to the diagnosis of LyP.

Race: Black persons may be less affected than other racial groups.

Sex: No consistent sex predominance is found in studies.

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

Presentation

Primary lesion: Each erythematous papule evolves into a red-brown, often hemorrhagic, papulovesicular or papulopustular lesion over days to weeks.

Some lesions develop a necrotic eschar before healing spontaneously. Occasionally, noduloulcerative lesions may be present

Each papule heals within 2-8 weeks, leaving a hypopigmented or hyperpigmented depressed oval varioliform 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.

Lymphomatoid Papulosis

Type A: Characterized by large (25-40 mm) CD30+ atypical cells with polymorphic convoluted nuclei and a minimum of 1 prominent nucleolus. These large cells resemble Reed-Sternberg cells when binucleate. Type A LyP is the most common histologic variant.

Type B: Characterized by smaller (8-15 mm) atypical cells with hyperchromatic cerebriform nuclei resembling the atypical lymphocytes in MF. CD30+ large cells are rare, but epidermotropism is more common in this variant.

Lymphomatoid Papulosis

Type C (diffuse large cell type): Characterized by sheets of CD30+ anaplastic large cells

Treatment of LyP

mid-to-high potency topical steroids to hasten resolution. Low-dose weekly methotrexate is a safe and effective

treatment for suppressing LyP; however, the disease recurs within 1-2 weeks after ending medication.

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

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

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-cell

lymphoma Non-MF CD30-negative cutaneous pleomorphic

small or medium sized cell lymphoma Subcutaneous (Panniculitis-Like) T-Cell

Lymphoma Nasal/Nasal Type T/NK Cell Lymphoma

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

Secondary CD30-positive cutaneous T-Cell Lymphoma CD30 Positive CTCL arise from MF Poor prognosis

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 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

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

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

High-power view of infiltrate showing random atypical lymphocytes

Cutaneous B-Cell Lymphoma

Primary Cutaneous Follicular Center Cell Lymphoma

Primary Cutaneous Immunocytoma Intravascluar Large B-Cell Lymphoma Plasmacytoma (Multiple Myeoloma)

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

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 yr surv.

Stains with B-Cell marker CD 20, monotypic for immunoglobulin production of kappa or lambda chain, not both

Primary Cutaneous Immunocytoma

AKA Marginal Zone B-Cell Lymphoma AKA MALT Type Lymphoma SubQ nodule or tumor primaroily of the

extremities or trunk CD79, CD 20, and bcl-2 positive 5 years survival near 100%

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 and infiltration of bone marry by plasma cells

Plasmacytoma Multiple Myeloma Cutaneous plasmacytomas seen most

commonly a secondary lesion in the setting of primary myeloma. Prognosis is poor.

When bone film and bone biopsy are normal but cutaneous lesions present, these are primary cutaneous plasmacytoma. Excellent prognosis.

Dense mononuclear infiltrate withinentire dermis.This represent a primary cutaneous

plasmacytoma

Neoplastic plasma cells, some with atypical

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

Plasmacytoma Multiple Myeloma Numerous nonspecific skin lesions occurs

in patient with multiple myeloma.AmyloidosisCutaneous vasculitisalopeciaRaynaud’sPyoderma gangrenosum

Hodgkin’s Disease

Vast majority of cutaneous Hodgkin’s disease report are type A lymphomatoid papulosis with Reed-Sternberg

Difficult to prove cutaneous disease

Malignant Histiocytosis

Rare, fatal occur in men in second to fourth decade of life

Solitary lesion or wide spread papule occur in 10% of cases

Onset of acute fever, hepatosplenomegly, and painful lymphadenopathy

Malignant histiocytosis. Extensive superior orbital involvement in a young adult male.

Extensive erythrophgocytosis by histiocyte in marrow, liver, spleen

Leukemia Cutis

30% of Leukemia patient will have leukemia cutis

Vast majority of derm manifestation are from AML

Morphology: 60% multiple papules and nodules, 26% of infiltrated plaques

Subtypes and variants: Granulocytic Sarcoma Hairy-cell Leukemia Nonspecific Condition associated with Leukemia

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

Hypereosinophilic Syndrome

Icrease Eos with more than 1500 eos per cubit millimeter for 6 month or more.

Cardiac disease most frequent complication

90% patient are men between 20 to 50 Angioedema and urticaria lesions most

common. Sometimes papules.

Angioimmunoblastic T-Cell Lymphoma AKA Angioimmunoblastic T-Cell

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

perivascular dermal infiltrate) Lymph node biopsy required for diagnosis

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