Primary Cutaneous Peripheral T cell Lymphomas Flashcards
What disease entities are contained
in this category because they are rare ?
- Primary cutaneous gamma/delta T cell lymphoma
- Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphoma
- Primary cutaneous acral CD8+ T cell lymphoma
- Primary cutaneous CD4+ small/medium T cell LPD
What is the definition of
PC G/D T cell lymphoma?
- primary to the skin
- mature, activated g/d T cells
- cytotoxic phenotype
IMP: G/D TCR may be seen in MF or Lymphomatoid papulosis so just because the G/D TCR is rearranged doesn’t mean it’s this entity.
What is the epidemiology of
PC G/D T cell lymphoma ?
- very rare, 1% of cuteneous T cell lymphomas
- most occur in adults
- no sex predilection
What is the etiology of
PC G/D T cell lymphoma ?
- distribution of the disease reflects normal G/D T cells which are essential in the innate immun response
- it is felt that this disease may arise from chronic antigenic stimulation
What is the localization of PC
G/D T cell lymphoma ?
- generalized skin lesions with variable clinical morphology (see pictures p. 397)
- primarily affect the extremities
What are the clinical features
of PC G/D T cell lymphoma?
- clinical presentation is variable with plaque like lesions (epidermotropic lesions) to deep dermal/subQ tumors
- usually on extremities but can be at other sites
- dissemination to mucosal or other areas is frequent with progression
- NO involvement of LN, spleen or bone marrow is usually identifed
- HLH often develops
- particularly with panniculitis like tumors
- B symptoms seen in most adults
What are the microscopic findings
of PC G/D T cell lymphoma ?
- 3 major patterns:
- epidermotropic
- dermal
- subcutaneous
- Epidermal infiltrate can be mild to marked
- SubQ shows rimming of fat cells
- similar to subcutaneous panniculitis like T cell lymphoma
- BUT this entity also has dermal/and or epidermal involvement
- medium to large in size
- large blastic or anaplastic cells are infrequent
- angioinvasion with apoptosis and necrosis is common
What is the immunophenotype of
PC G/D T cell lymphoma?
- delta TCR gene positive
- CD3 and CD2+
- CD7 +/- and CD56+
- CD5 -
- strong expression of cytotoxic proteins:
- TIA1, Granzyme B and Perforin
- CD4 and CD8 are both usually negative
- CD8 may be expressed in some cases
What is the postulated normal counterpart
of PC G/D T cell lymphoma ?
- functionally mature and activated cytotoxic G/D T cells
- of the innate immune system
What is the genetic profile
of PC G/D T cell lymphoma ?
- TRG and TRD genes are clonally rearranged
- V delta 2, consistent with prevalence of these residing in the skin
- EBV is negative
- STAT5B and rarely STAT3 can have activating mutations
- which makes sense because many cytotoxic T cell malignancies have activation of the JAK/STAT pathway
What are the prognostic and predictive
factors for PC G/D T cell lymphoma?
- usually resistent to multiagent chemotherapy and radiation
- median survival is 15 months
- poor prognosis
- subcutaneous lesions are particularly bad
What is the definition of PC CD8+
aggressive epidermotropic cytotoxic T cell lymphoma ?
- provisional entity
- proliferation of CD8+ cytotoxic T cells with marked epidermotropism and epidermal necrosis
- what differentiates this entity from other CD8+ cutaneous T cell lymphomas is:
- clinical presentation
- clinical behavior
- histologic features
What is the epidemiology of PC
CD8+ aggressive epidermotropic
cytotoxic T cell lymphoma?
- very rare disease ( < 1% of all cutaneous lymphomas)
- occurs mainly in adults
- no known predisposing factors
What is the localization of PC CD8+
aggressive epidermotropic cytotoxic T cell lymphoma ?
- most patients present with generalized skin lesions
What is the clinical presentation of PC CD8+
aggressive epidermotropic cytotoxic T cell
lymphoma?
- disseminated, eruptive papules, nodules and/or tumors with central ulceration and necrosis
- rarely it presents as a localized lesion
- IMP:
- these lymphomas can disseminate to other visceral sites:
- lungs, testes, CNS, oral mucosa
- LN are often spared
- these lymphomas can disseminate to other visceral sites:
What are the microscopic features of PC, CD8+
aggressive epidermotropic cytotoxic
T cell lymphoma ?
- variable morphology
- can have a lichenoid pattern with marked pagetoid epidermotropism and subepidermal edema
- or deeper dermal infiltrates with barely any epidermotropism (more likely seen in the localized variant)
- epidermis shows necrosis, ulceration and blister formation
- destruction of adnexal structures is common
- tumor cells
- small-medium-large
- blastic or pleomorphic nuclei are common
What is the immunophenotype of PC
CD8+ aggressive, cytotoxic, epidermotropic
T cell lymphoma ?
- CD3+, CD8+, CD4-
- alpha Beta F1 +
- Granzyme B+, Perforin +, TIA1+
- CD45RA+, CD45RO-
- CD2 and CD5-
- CD7 variable expression
- CD30 - in most cases
IMP: difficult clinically and by immunophenotype to differentiate from lymphomatoid papulosis (type D)
What is the normal counterpart of
PC CD8+ aggressive epidermotropic
cytotoxic T cell lymphoma ?
- a skin-homing, CD8+ cytotoxic T cell
- alpha beta type
What is the genetic profile of PC CD8+
aggressive epidermotropic cytotoxic
T cell lymphoma ?
- specific genetic abnormalities have not been identified
- No EBV ISH
What is the prognosis and predictive factors
for PC CD8+ aggressive epidermotropic
cytotoxic T cell lymphoma ?
- aggressive disease with median survival of 12 months
- no difference in clinical outcome between large and small cell morphology and generalized or localized variant
What is the definition of PC acral CD8+
T cell lymphoma ?
- Rare, cutaneous tumor composed of a skin infiltration of atypical medium-sized cytotoxic lymphocytes
- preferential involvement of acral sites, particularly the ears
- associated with a good prognosis
What is the epidemiology of
PC CD8+ acral T cell lymphoma ?
- disease of adults
- median age is 53 years
- male predominance is seen
What is the etiology of PC
CD8+ acral T cell lymphoma ?
- unknown etiology
- an infectious agent is suspected but has not been proven
What are the clinical features of
PC CD8+ acral T cell lymphoma?
- generally a localized lesion
- reddish papule or nodule
- slow growing over weeks to months
- most frequent sites: ear > nose > foot
- rarely can have multiple lesions or bilateral lesions of the same site
What are the microscopic features of
PC CD8+ acral T cell lymphoma ?
- monotonous dermal infiltration of medium sized lymphocytes
- they have irregular, frequently folded nuclei and small nucleoli
- mitoses and apoptoses are rare
- reactive B lymphoid aggregates of follicles may be interspersed with this infiltrate
- other inflammatory cells should be rare or absent (eos, histiocytes, etc)
- epidermis is spared with a grenz zone
- underlying adipose tissue is almost always involved
- skin appendages are always spared
- angiodestruction and necrosis are never seen
What is the immunophenotype of PC
CD8+ acral T cell lymphoma ?
- CD3, CD8, TIA-1 and beta F1 are positive
- TIA-1 shows golgi like staining pattern
- CD2, CD5 and CD7 are regularly positive but may be weak or lost
- CD4 always negative
- Granzyme and Perforin are usually negative
- CD56, CD57, CD30, TdT, EBV and TFH cell markers are negative
- CD68
- frequently patchy positive with golgi like pattern of staining
- Ki67
- usually <10%
- if >50% consider a different lymphoma
What is the postulated normal counterpart of
PC CD8+ acral T cell lymphoma ?
- CD8+ skin homing T cell
- but other locations of have been described including the GI tract
- thought to now be a CD8+ memory T cell
What is the genetic profile of PC
CD8+ acral T cell lymphoma ?
- specific genetic alterations have not yet been described
- EBV is negative
What are the prognostic and predictive factors
of PC CD8+ acral T cell lymphoma ?
- this lymphoma has a very good prognosis
- complete remission after surgical excision or local radiation
- no evidence of dissemination
- local recurrence may happen
- NO chemotherapy is needed
What is the definition of PC
CD4+ LPD ?
- small/medium size cells with pleomorphic morphology
- present with a solitary skin lesion without evidence of plaques or patches of MF
- similar clinical presenation to cutaneous pseudo- T cell lymphoma with a nodular growth pattern
What are the epidemiology and localization for
PC CD4+ T cell LPD ?
- rare disease, ~2% of all skin T cell lymphomas
- usually present as a solitary plaque or nodule
- common on the face, neck or upper trunk
What are the clinical features of PC
CD4+ T cell LPD ?
- patients are usually asymptomatic
- single slow-growing lesion
- rare cases have multiple lesions
- No clinical evidence of MF should be seen
What are the microscopic findings for PC
CD4+ T cell LPD ?
- dense or diffuse or nodular infiltrates within the dermis and a tendency to infiltrate the subcutis
- epidermotropism can be focally present
- IF conspicuous the diagnosis of MF should be considered
- cytology
- predominance of small/medium pleomorphic T cells
- <30% can be large and pleomorphic
- CD4+ T cells are usually admixed with small, reactive CD8+ T cells, B cells, PC, and histiocytes, including multinucleated giant cells
What is the immunophenotype of PC CD4+
T cell LPD ?
- CD3+, CD4+, CD8-, CD30-
- Loss of pan T cell antigens (except for CD7) is uncommon and cytotoxic proteins are not expressed
- atypical T cells express:
- PD1, BCL6 (variable), and CXCL13 suggesting TFH derivation
- CD10 is negative
- Ki67 is usually low 5-20% at most
What is the postulated normal counterpart
for PC CD4+ T cell LPD ?
- skin-homing CD4+ T cell with TFH-cell characteristics
What is the genetic profile of PC
CD4+ T cell LPD ?
- TCR genes are usually clonally rearranged
- specific genetic abnormalities have not been identified
- EBV is negative
What are the prognostic and predictive factors
for PC CD4+ T cell LPD ?
- excellent prognosis
- intralesional steroids, surgical excision or radiotherapy are preferred treatments
- local recurrences are rare
