Nccn clinical practice guidelines in oncology (nccn guidelines®) non-hodgkin’s lymphomas

NCCN Guidelines Version 1.2014
Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders
OVERVIEW & DEFINITION
· Primary cutaneous CD30+ T-cell lymphoproliferative disorders · Primary cutaneous ALCL (PC-ALCL)
(LPDs) represent a spectrum that includes primary cutaneous
> Represents about 8% of cutaneous lymphoma cases.b
ALCL, lymphomatoid papulosis, and “borderline” cases with
> Unlike systemic ALCL, PC-ALCL typically follows an indolent course and
overlapping clinical and histopathologic features.a,b
although cutaneous relapses are common an excellent prognosis is
Clinical correlation with histopathologic features is essential
usually maintained.
for establishing the diagnosis of primary cutaneous CD30+ T-
> Histologically characterized by diffuse, cohesive sheets of large CD30-
cell LPDs; diagnosis cannot be made based on pathology
positive (in >75%) cells with anaplastic, pleomorphic, or immunoblastic
review alone.
appearance.
> Clinical features typically include solitary or localized nodules or tumors
Differential diagnosis
(often ulcerated); multifocal lesions occur in about 20% of cases.
· It is critical to distinguish CD30+ T-cell LPDs from other CD30+
Extracutaneous disease occurs in about 10% of cases, usually involving
processes involving the skin that include:
regional lymph nodes.
> Systemic lymphomas (eg, systemic ALCL, ATLL, PTCL),
> Except in rare cases, PC-ALCL is ALK-
> Other cutaneous process such as other CD30+ skin
lymphomas such as mycosis fungoides (MF), especially
· Lymphomatoid papulosis (LyP)
transformed MF, cytotoxic T-cell lymphomas, and
> LyP has been classified (WHO-EORTC) under lymphomas but may be
> Benign disorders such as lymphomatoid drug reactions,
best classified as a LPD as it is a uniformly spontaneously regressing
arthropod bites, viral infections and others.
process.
· Lymphomatoid drug reactions has been linked with certain
> LyP has been reported to be associated with other lymphomas such as
drugs (eg, amlodipine, carbamazepine, cefuroxime, valsartan)
MF, PC-ALCL, systemic ALCL, or Hodgkin lymphoma.
and is associated with CD30+ atypical large cells in histology
Histologically heterogenous with large atypical anaplastic,
· MF and primary cutaneous CD30+ T-cell LPD can coexist in
immunoblastic, or Hodgkin-like cells in a marked inflammatory
the same patient.
background; several histologic subtypes (types A to D, with CD30-
positive cells) defined based on evolution of skin lesions.d
> Clinical features characterized by chronic, recurrent spontaneously
regressing papulonodular (grouped or generalized) skin lesions.a,b,d
a Ralfkiaer E, Willemze R, Paulli M, Kadin ME. Primary cutaneous CD30-positive T-cell lymphoproliferative disorders. In: Swerdlow SH, Campo E, Harris NL, et al., eds. WHO classification of tumours of haematopoietic and lymphoid tissues Kempf W, Pfaltz K, Vermeer MH, et al. EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive b Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous lymphomas. Blood 2005;105:3768-3785.
anaplastic large-cell lymphoma. Blood 2011;118:4024-4035.
c Benner MF, Willemze R. Applicability and prognostic value of the new TNM Due to overlapping immunophenotype and morphology classification system in 135 patients with primary cutaneous anaplastic large cell diagnose CD30+ T-cell in lymph nodes as HL (Eberle FC, Song JY, Xi L, et al. Nodallymphoma. Arch Dermatol 2009;145:1399-1404.
involvement by cutaneous CD30-positive T-cell lymphoma mimicking classicalHodgkin lymphoma. Amer J Surg Pathol 2012;36:716-725.) Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 1.2014, 12/20/13 National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN .
NCCN Guidelines Version 1.2014
Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders
DIAGNOSIS
ESSENTIAL:
· Clinical presentation: see Overview and Definition
· Clinical pathologic correlation is essential
· Complete skin examination for evidence of MF
· Cutaneous anaplastic large cell
Biopsy of suspicious skin sites
lymphoma (ALCL)
Histopathology review of adequate biopsy (punch,
· Lymphomatoid papulosis (LyP)j
incisional, excisional).
> Review of all slides with at least one paraffin block
representative of the tumor should be done by a
pathologist with expertise in the diagnosis of cutaneous
T-cell lymphoma. Rebiopsy if consult material is
nondiagnostic.
· Adequate immunophenotyping to establish diagnosisf,g on
skin biopsy:
> IHC: CD3, CD4, CD8, CD20, CD30, CD56, βF1, ALK1h
USEFUL UNDER CERTAIN CIRCUMSTANCES:
· On skin biopsy:
> Expanded IHC: CD2, CD5, CD7, CD25, TIA1, granzyme B,
perforin, GM1, EBER-ISH
> Molecular analysis to detect: gene rearrangements: TCRi
CD30+ transformed
(assessment of clonality)
mycosis fungoides
· Excisional or incisional biopsy of suspicious lymph nodes
(in absence of definitive skin diagnosis)
· Assessment of HTLV-1 serology in at-risk populations to
identify CD30+ ATLL
g g Typical immunophenotype: CD30+ (>70% cells),CD4+ variable loss of CD2/CD5/CD3,CD8+ (<5%) cytotoxic granule proteins positive.
h ALK1 positivity and t(2;5) translocation is typically absent in PC-ALCL and LyP.
i TCR gene rearrangement results should be interpreted with caution. TCR clonal rearrangement can be seen in non-malignant conditions or may not be demonstrated in all cases of MF/SS. Demonstration of identical clones in skin, blood, and/or lymph node may be helpful in selected cases.
j LyP is not considered a malignant disorder; however, there is an association with other lymphoid malignancy (mycosis fungoides, classical Hodgkin lymphoma, or LCL) and staging studies are only done to rule out suspicion of systemic disease.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 1.2014, 12/20/13 National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN .
NCCN Guidelines Version 1.2014
Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders
ESSENTIAL:
USEFUL IN SELECTED CASES:
cutaneous
Complete physical examination
· Pregnancy testing in women of child-
including entire skin;k palpation of
bearing agen
peripheral lymph node regions; liver
· Bone marrow aspiration and biopsy
or spleen enlargement
optional for solitary C-ALCL or C-ALCL
Cutaneous
Cutaneous
· CBC, differential
without extracutaneous involvement
ALCL with
· Comprehensive metabolic panel
on imaging
regional node
· Chest/abdominal/pelvic contrast-
enhanced CT or integrated whole
body PET-CT
· Biopsy suspicious nodese,l,m
Systemic ALCL
ESSENTIAL:
USEFUL IN SELECTED CASES:
· Complete physical examination
· Pregnancy testing in women of child-
including entire skin;k palpation of
bearing agen
peripheral lymph node regions;
· Chest/abdominal/pelvic contrast-
liver or spleen enlargement
enhanced CT or integrated whole body
· CBC, differential
· Comprehensive metabolic panel
· Bone marrow aspiration and biopsy
(not done for typical LyP)j,o
e Due to overlapping immunophenotype and morphology, need to use caution to not diagnose CD30+ T-cell in lymph nodes as HL (Eberle FC, Song JY, Xi L, et al.
Nodal involvement by cutaneous CD30-positive T-cell lymphoma mimicking classical Hodgkin lymphoma. Amer J Surg Pathol 2012;36:716-725.) j LyP is not considered a malignant disorder; however, there is an association with other lymphoid malignancy (mycosis fungoides, classical Hodgkin lymphoma, or PC-ALCL). Staging studies are done in LyP only if there is suspicion of systemic involvement by an associated lymphoma.
k Monitoring the size and number of lesions will assist with response assessment.
l Consider systemic ALCL, regional lymph node involvement with PC-ALCL, or lymph node involvement with transformed MF.
m Consider PC-ALCL if in draining lymph nodes only.
n Many skin-directed and systemic therapies are contraindicated or of unknown safety in pregnancy. Refer to individual drug information.
o Only done to exclude an associated lymphoma.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 1.2014, 12/20/13 National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN .
NCCN Guidelines Version 1.2014
Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders
EXTENT OF
FOLLOW-UPs
RELAPSE/REFRACTORY
TREATMENT
· Retreat with initial treatment
Observe for
Solitary or
Surgical excision ± RTq
Response
if disease confined to skin
recurrence
· For multifocal lesions or
No response/
extracutaneous
refractory
involvement, see below
Methotrexate (£100 mg weekly)
cutaneous
Observe for
Responset
recurrence
Systemic retinoidsr
Multifocal
Pralatrexate
· Clinical trial
· Treat with same (unless
Observation, if asymptomatic
refractory or intolerant)
No response/
refractory
Interferon alpha (category 2B)
· Alternative regimen not
used for primary treatment
Methotrexate ± RTq
· Mycosis fungoides
“Category C Systemic
Observe for
Pralatrexate ± RTq
Response
Therapies” (SYST-CAT C)
Cutaneous ALCL with
recurrence
regional node (excludes
CHOP or CHOEP ± RTq
systemic ALCL)
in selected cases
No response/
refractory
RTq in selected cases
t Patients achieving a response and/or a clinical benefit with cutaneous disease should be p Regression of lesions may occur in up to 44% of cases.
considered for maintenance or taper regimens to optimize response duration. Patients who relapse often respond well to the same treatment. Patients with a PR should be r Limited data from case reports (eg, bexarotene).
treated with the other options in the primary treatment list to improve response before s Mycosis fungoides can develop over time; continue to conduct thorough moving onto treatment for refractory disease. Patients with relapse or persistent disease after initial primary treatment may be candidates for clinical trials.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 1.2014, 12/20/13 National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN .
NCCN Guidelines Version 1.2014
Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders
EXTENT OF
FOLLOW-UPv
RELAPSE/REFRACTORY
TREATMENT
Continue
Asymptomatic
observation
Observation (preferred for
asymptomatic)
Topical steroids
Limited lesions or
asymptomatic
Topical steroids
or
Treat with alternative
Phototherapy
regimen not used for
Symptomatic
primary treatment
or
Other regimens
Observation
or
Responsew
Observe for
Clinical trial
Methotrexate [10-35 mg weekly )
recurrence
Observation
Extensive
Phototherapy
lesions or
Retreat or treat with
symptomatic
Systemic retinoidsr
alternative regimen not
used for primary
Topical steroids
No response/
treatment
refractory
Topical nitrogen mustard
r Limited data from case reports (eg, bexarotene).
u Kempf W, Pfaltz K, Vermeer MH, et al. EORTC, ISCL, and USCLC consensus w Patients achieving a response and/or a clinical benefit may be considered for recommendations for the treatment of primary cutaneous CD30-positive maintenance or taper regimens to optimize response duration. Patients who relapse lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous often respond well to the same treatment. Patients with a PR should be treated with anaplastic large-cell lymphoma. Blood 2011;118:4024-4035.
the other options in the primary treatment list to improve response before moving v Life-long follow up is warranted due to high risks for second lymphoid onto treatment for refractory disease. Patients with relapse or persistent disease malignancies; continue to conduct thorough skin exam during follow-up.
after initial primary treatment may be candidates for clinical trials.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Version 1.2014, 12/20/13 National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN .

Source: http://cutaneouslymphoma.stanford.edu/docs/nhl_1.2014_PCTLD.pdf