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

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

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

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

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

Lymphomatoid Papulosis 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

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

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

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

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

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

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%

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

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

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

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