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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 - PowerPoint PPT Presentation
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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
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
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
Primary CBCLPrimary CTCLIndolent
Follicle center cell lymphoma
Immunocytoma (marginalzone B-cell lymphoma)
IntermediateLarge B-cell Lymphoma of
the leg
IndolentMF
MF + 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
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
Primary CBCLPrimary CTCLIndolent
Follicle center cell lymphoma
Immunocytoma (marginalzone B-cell lymphoma)
IntermediateLarge B-cell Lymphoma of
the leg
IndolentMFMF + follicular mucinosis
Pagetoid 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
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
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
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
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 PapulosisAggressive
SSLarge cell CTCL, CD30-
Immunoblastic,Pleomorphic
ProvisionalIntravascular large B-cell
lymphomaPlasmacytoma
ProvisionalGranulomatous slack skinCTCL, pleomorphic small/
medium-sizedSubcutaneous panniculitis-like
T-cell lymphoma
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
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
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
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
AggressiveSS
Large cell CTCL, CD30-Immunoblastic,Pleomorphic
ProvisionalIntravascular large B-cell
lymphomaPlasmacytoma
ProvisionalGranulomatous slack skinCTCL, pleomorphic small/
medium-sizedSubcutaneous panniculitis-like
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
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
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
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 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
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
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
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
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
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
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
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
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
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
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
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
lymphoma
Plasmacytoma
ProvisionalGranulomatous slack skinCTCL, pleomorphic small/
medium-sizedSubcutaneous panniculitis-like
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