Primary Cutaneous Lymphoma

Primary Cutaneous Lymphoma

• Heterogeneous group of T and B-cell lymphomas

• variation in– clinical presentation– histology– immunophenotype– prognosis

• Incidence 0.5-1/100,000/year

• Classified according to – updated Kiel Classification– Working Formulation– REAL Classification

• Treated as – Lymphoma of Lymph Nodes– ? What about indolent cutaneous lymphomas

Primary Cutaneous Lymphoma

• Definition: patients without concurrent extracutaneous disease at the time of diagnosis– characteristic clinical and histologic features– different behavior and prognosis– different translocation and oncogenes

• Difficulties:

• Primary cutaneous lymphomas cannot be defined properly by histologic criteria alone.

• Example : – CD30-positive and CD-negative T-cell lymphomas– Lymphoid papulosis and Mycosis Fungoides

• Classification needs– Histology– Clinical presentation– Immunology

• European Organization for Research and Treatment of Cancer “EORTC”– Clinically relevant classification

– Primary cutaneous lymphoma is defined as non-Hodgkin Lymphomas presenting in the skin with no evicence of extracutaneous desease at the time of diagnosis and within the first 6 month.

– Exclude secondary lymphomas, Lymphoma in immunocompromised patients, and HTLV-1 associated adult T-cell lymphoma

Primary CBCLPrimary CTCLIndolent

Follicle center cell lymphoma

Immunocytoma (marginalzone B-cell lymphoma)

IntermediateLarge B-cell Lymphoma of

the leg

IndolentMFMF + follicular mucinosisPagetoid reticulosis

Large Cell CTCL, CD30+Anaplastic,ImmunoblasticPleomorphic

Lymphomatoid Papulosis

AggressiveSSLarge cell CTCL, CD30-

Immunoblastic,Pleomorphic

ProvisionalIntravascular large B-cell

lymphomaPlasmacytoma

ProvisionalGranulomatous slack skinCTCL, pleomorphic small/

medium-sizedSubcutaneous panniculitis-like

T-cell lymphoma





the leg










T-cell lymphoma

Mycosis Fungoides

• Epidermotropic CTCL characterized by a proliferation of small or medium-sized neoplastic T lymphocytes with cerebriform nuclei

• Indolent clinical course– slow progression over years– patches, plaques, tumors, lymph node, internal

organs

• Epidermotropic, band-like infiltrates involving the papillary dermis

• small, medium-sized, and occasionally large mononuclear cells

• hyperchromatic, indented (cerebriform) nuclei

• Pautrier’s microabscesses

• CD3+, CD4+, CD45RO+,CD8-, CD30-

• 5-year survival 87%

• Therapy:– confined to skin: skin-targeted therapies,

phototherapy, topical nitrogen mustard, radiotherapy

• Progression to CD30+ or CD30- Large T-cell lymphoma

MF specific Variants

• Classical Alibert-Bazin type– Bullous, hyper or hypopigmented MF

• MF with follicular mucinosis

• Pagetoid reticulosis

• Granulomatous slack skin





the leg

IndolentMF

MF + follicular mucinosisPagetoid reticulosis









T-cell lymphoma

MF-Associated Folliular Mucinosis

• Definition:– Folliculotropic infiltrates with sparing of the

epidermis– mucinous degeneration of the hair follicles– preferential involvement of the head and neck

• Clinically: – follicular papules, indurated plaques, and tumor– associated with hair loss , pruritus

• Micro:– perivascular and periadnexal localization of the dermal

infiltrates– infiltration of the follicular epithelium– medium-sized to large hyperchromatic cells with

cerebriform nuclei– sparing of the epidermis– mucinous degeneration of the follicular epithelium

• Survival 70%• Therapy: total skin electron beam





the leg

IndolentMFMF + follicular mucinosis

Pagetoid reticulosis









T-cell lymphoma

Pagetoid Reticulosis

• Localized “Woringer-Kolopp”

• ?Disseminated “Ketron-Goodman”

• Definition: localized patches or plaques with an intraepidermal proliferation of neoplastic T cells

• Slowly growing psoriasiform or hyperkeratotic patch.

• Micro:– acanthosis – large atypical pagetoid cells– medium-sized to large with hyperchramatic

cerebriform nuclei– CD3+, CD4+, CD8-, or CD3+, CD4-, CD8+

• Therapy: radio or surgery

• prognosis : excellent





the leg










T-cell lymphoma

CD30+ Lymphoproliferative Disorders

• Include:– CD30+ large T-cell lymphoma– Lymphomatiod papulosis (LyP)– ? Borderline Cases

CD30+ large T-cell lymphoma

• Large tumor cells, CD30+

• no history or evidence of MF or LyP

• most 80% has features of Anaplastic Large cell lymphoma

• others immunoblastic, pleomorphic

• adult M:F 3:2

• Solitary localized (ulcerating) nodule

• Micro:– diffuse non-epidrmotropic– Anaplastic, or pleomorphic or , immunblastic

• immuno:– CD30+(>75%), CD4+, CD2-, CD3-, CD5-,

CD15-,EMA-

• Survival: 90%• Treatment : localized-radio, generalized-chemo





the leg



Lymphomatoid PapulosisAggressive

SSLarge cell CTCL, CD30-






T-cell lymphoma


• Chronic, recurrent, self-healing papulonodular skin eruption with histologic features of CTCL

• 10-20% associated with others (MF, CD30+ large T-cell lymphoma, or Hodgkin’s)

• Micro:– type A: wedge-shaped, initially non-

epidermotropic , large atypical, CD30+ cells with extensive infiltrates of histiocytes, small lymphocytes and eosinophils

– Type B: perivascular or bandlike, epidermotropic infiltrates with small to medium-sized cells with cerebriform nuclei

– Type C: features suggestive of CD30+ large T-cell lymphoma.

• Immuno– Type A and Type C: similar to CD30+ large T-

cell , CD3+, CD4+/-, CD5+/-, CD8-, CD30+, CD15-, EMA-

– Type B: CD3+,CD4+, CD8-, CD30-

• Survival : 100%

• no cure, relapse after treatment





the leg










T-cell lymphoma

Sezary’s Syndrome• Definition:

– erythroderma, generalized lymphadenopathy, and the presence of neoplastic T cells in skin, lymph nodes and peripheral blood

• Micro:– may be similar to MF– more often monotonous cells– CD3+, CD4+, CD45RO+, CD8-, CD30-

• Survival: 11%, Chemo is the treatment





the leg




AggressiveSS

Large cell CTCL, CD30-Immunoblastic,Pleomorphic





T-cell lymphoma

CD30- Large Cell Lymphoma• CD30- large neoplastic cells without MF

• solitary, localized, or generalized plaques, nodules, or tumors.

• Micro:– medium-sized to large pleomorphic T cells with or

without cerebriform nuclei and immunoblasts– CD4+ only, CD30-– Survival : 15%

• Chemo is recommended





the leg










T-cell lymphoma

Granulomatous Slack Skin• Definition:

– slow development of folds of lax skin and a granulomatous infiltrated with clonal T cells

• axillae groins , Male predominant• ?association with Hodgkin’s , and MF• Micro:

– dense granulomatous dermal infiltrates – atypical T cells with cerebriform nuclei– CD3+ , CD4+, CD8-– Survival : indolent course





the leg








ProvisionalGranulomatous slack skin

CTCL, pleomorphic small/medium-sized

Subcutaneous panniculitis-likeT-cell lymphoma

Pleomorphic Small/Medium-Sized CTCL

• Definition: – neoplastic proliferation of pleomorphic

small/medium-sized Tcells – clinical picture different form MF

• Micro:– dense, diffuse or nodular infiltrates of small/medium

pleopmorphic neoplastic T cells– CD4+, CD8+(some), loss of pan Tcell markers

• Favorable prognosis





the leg










T-cell lymphoma

Subcutanious Panniculitis-Like T-Cell Lymphoma

• Definition– subcutaneous infiltrates of small, medium-sized

or large pleomophic T cells and many macrophages

• Clinically– subcutaneous nodules mainly on legs– systemic symptoms fever, weight loss..– Hemophagocytic syndrome

• Micro:– panniculitis-like infiltrates with neoplastic T

cells and macrophages– tumor cell necrosis, karyorrhexis ,

erythrophagocytosis– CD3+, CD4+, CD8-– or CD3+, CD4-, CD8+

• Poor prognosis

Primary CBCLPrimary CTCL

IndolentFollicle center cell

lymphoma



the leg










T-cell lymphoma

Follicular Center Cell Lymphoma

• Definition:– follicle center cells, centrocytes (small and large

cleaved) and cetroblasts (large with prominent nucleoli)

• Clinically:– non scaling , solitary or grouped papules, plaques

or tumors– Head , neck and trunk– dissemination is uncommon

• Micro:– nodular of diffuse infiltrates sparing the epidermis– Early lesions: centrocytes , few centrobasts, many

T cells, neoplastic follicles are rare (follicular center lymphoma)

– Late lesions: monotonous infiltrates of large centrobalsts and centrocytes (large B cell lympnoma)

– CD19+, CD20+, CD22+, CD79a+– CD5-, CD10-– rarely express bcl-2

• Survival: 97%

Primary CBCLPrimary CTCL

IndolentFollicle center cell lymphoma



the leg










T-cell lymphoma

Immunocytoma (Marginal Zone B-Cell Lymphoma)

• Definition:– small lymphocytes, lymphoplasmacytoid cells

and plasma cells– monotypic cIg

• Clinically:– solitary or multiple (sub)cutaneous tumors

• Micro:– nodular or diffuse infiltrates of lymphocytes,

lymphoplasmacytoid cells and plasma cells– monotypic cIg+, CD79a+, CD5-, plasma cells

are CD20-

• Survival : 100%

• Therapy: radiotherapy is recommended





the leg










T-cell lymphoma

Large B-Cell lymphoma of Leg

• Definition: – Large B cell presenting on and confined to leg

• Clinically:– elderly >70y (80%) of cases– F:M 3-4:1– tumor nodule on one or both legs

• Micro:– diffuse nonepidermotropic infiltrates – large B cells– sIg+ and or cIg, CD19+, CD20+, CD22+ and

CD79a+– Strong bcl-2

• Survival: 58%

• Therapy: radio or chemo





the leg










T-cell lymphoma

Intravascular Large B-Cell Lymphoma

• Definition: – (Malignant angioendotheliomatosis)– large neoplastic B cells within blood vessels

• Clinically:– violaceous indurated patches and plaques– usually on the lower leg or the trunk

• Micro:– dilated blood vessels – filled with large neoplastic lymphoid cells– 20% extra vascular accumulation– CD19+, CD20+, CD22+, CD79a+, monotypic

sIg+

• Survival: 50%

• Therapy : chemo





the leg







lymphoma

Plasmacytoma



T-cell lymphoma

Plasmacytoma

• Definition:– clonal proliferation of plasma cells that

develops primarily in the skin– without multiple myeloma

• Clinically:– solitary or multiple red to violaceous nodules

• Micro: – mature plasma cells, monotypic cIg+, CD38+,

LCA-, CD20-

• no deaths reported

• Therapy: surgical or radio

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Primary Cutaneous Lymphoma