1/14/2018. Objectives
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1 2018 Pathology CME Cutaneous Hematopathology Maui, HI Jan 18 th 26 th Pseudolymphomas Alejandro A. Gru, M.D. Assistant Professor of Pathology & Dermatology Dermatopathology Division and Fellowship Director University of Virginia Charlottesville, VA Conflicts of Interest disclosure: -Seattle Genetics: consultant, advisory board in CTCL, lecturer (SOLAR program) -Bristol-Meyer Squibb: consultant, advisory board Objectives Understand common clinical and histopathologic differential conditions that could mimic common CTCLs Understand common clinical and histopathologic differential conditions that could mimic common CBCLs Evaluate frequent non-hematologic tumors that could be accompanied by a rich lymphoid infiltrate Use of molecular and ancillary techniques that can help in the differential between cutaneous lymphomas and reactive infiltrates 1
2 What is a Pseudolymphoma? Benign lymphoid proliferations Inflammatory lesions Non-lymphoid tumors Benign vs malignant lymphoid infiltrates Lymphoid infiltrates vs nonlymphoid infiltrates Benign lymphoid infiltrates Cutaneous lymphoid hyperplasia Tattoo reactions Maybe it could get a little more complex. Cutaneous lymphoid hyperplasia of B-cells, T-cells, and mixed T/B-cells. Borrelia burgdorferiassociated lymphocytoma cutis. Atypical lymphoid hyperplasia. Atypical marginal zone hyperplasia. Lymphomatoid keratosis. Syringolymphoid hyperplasia with alopecia. Causes of CLH 2
3 Cutaneous B-cell hyperplasias Aka lymphocytoma cutis Clinical: Flesh colored to plum-red subcutaneous nodules and plaques similar to CBCLs Face, chest and upper extremities Female to male ratio is 3:1 2/3 <40 years of age Localized 72% Generalized 28% Histopathology: Top heavy infiltrate of mature lymphocytes with sparing of the epidermis Nodular; nodular and diffuse or diffuse Germinal centers and well-defined follicles Polarized GCs Cutaneous B-cell LH Cutaneous B-cell LH 3
4 Cutaneous B-cell LH Cutaneous B-cell LH CD3 CD20 Cutaneous B-cell LH BCL-6 BCL-2 4
5 Cutaneous B-cell LH Ki67 Cutaneous B-cell LH KAPPA LAMBDA Cutaneous B-cell LH in paraphenylenediamine Am J Dermatopathol
6 Cutaneous B-cell LH in syphilis CD3 CD20 Problem case: RLH? Problem case: RLH? 6
7 Problem case: RLH? Problem case: RLH? CD3 CD20 Problem case: RLH? BCL-6 BCL-2 7
8 Problem case: RLH? KI67 Problem case: RLH? ISH-KAPPA Problem case: RLH? ISH-LAMBDA 8
9 Other cutaneous B-cell LH with abundance of plasma cells Cutaneous Rosai-Dorfman disease (RDD) Cutaneous plasmacytosis Cutaneous Castleman s disease Cutaneous IgG4-related sclerosing disease Cutaneous IgG4-related disease LN, skin, lung and pancreatic involvement Autoimmune pancreatitis Sclerosing cholangitis Sclerosing sialadenitis LN often show Castlemanlike changes >15 PC/hpf IgG4/IgG ratio >40% Fibrosis, phlebitis Other diseases linked to IgG4: pemphigus vulgaris Hum Pathol 2009 Cutaneous IgG4-related disease 9
10 Cutaneous IgG4-related disease IgG4 Cutaneous Castleman Disease Most cases of CD present in HIV- patients 5-10% are HIV+ and typically associated with HHV-8 infection Cutaneous involvement in CD is very rare (<15 cases reported) LAD, hyperproteinemia, hypergammaglobulinemia, systemic symptoms, POEMS Skin: multiple erythematous to brownish nodules Histopathology: hyaline vascular type (90%), plasma cell (10%), mixed Cutaneous Castleman Disease 10
11 Cutaneus CD Plasma cell vulvitis / Zoon s balanitis Plasma cell vulvitis / Zoon s balanitis 11
12 Plasma cell vulvitis / Zoon s balanitis Cutaneous T-cell LH Three main histologic patterns Superficial diffuse (MF-like) Nodular Superficial and deep diffuse (arthropod bite-like) Superficial diffuse pattern Band-like infiltrate of small T-cells in the papillary dermis with blurring of the DEJ Acanthosis, psoriasiform changes, lymphocyte exocytosis, Occasional Pautrier-like collections Nodular pattern Infiltrate of T-cells with accompanying histiocytes, plasma cells, mast cells and eosinophils Minimal atypia of the lymphocytes Lymphomatoid drug reactions Arthropod-like pattern Variable acanthosis Superficial and deep, perivascular and interstitial pattern, with mixed lymphocytes, histiocytes, plasma cells and eos Sometimes large RS-like cells Frequently CD30 pseudolymphomas Cutaneous T-cell LH 12
13 Cutaneous T-cell LH Cutaneous T-cell LH Cutaneous T-cell LH CD3 CD20 13
14 Cutaneous T-cell LH CD4 CD8 Cutaneous T-cell LH CD7 CD30 Cutaneous T-cell LH MF-like 14
15 Cutaneous T-cell LH MF-like Cutaneous T-cell LH MF-like CD3 CD8 DIAGNOSIS: LSEA Pagetoid Reticulosis-Like 15
16 Pagetoid Reticulosis-Like Pagetoid Reticulosis-Like Pagetoid Reticulosis-Like 16
17 Pagetoid Reticulosis-Like Pagetoid Reticulosis-Like CD3 CD7 Pagetoid Reticulosis-Like CD4 CD8 17
18 Pagetoid Reticulosis-Like Pagetoid Reticulosis-Like Verruca Vulgaris Cutaneous T-cell LH (NODULAR) 18
19 Cutaneous T-cell LH (NODULAR) Cutaneous T-cell LH (NODULAR) Cutaneous T-cell LH (NODULAR) CD3 CD20 19
20 Cutaneous T-cell LH (NODULAR) CD43 CD7 Cutaneous T-cell LH (NODULAR) PD-1 Cutaneous T-cell LH (NODULAR) 20
21 Cutaneous T-cell LH (NODULAR) Cutaneous T-cell LH (NODULAR) CD3 CD20 DIAGNOSIS: VACCINE REACTION Cutaneous T-cell LH diffuse 21
22 Cutaneous T-cell LH diffuse Cutaneous T-cell LH diffuse Cutaneous T-cell LH diffuse CD3 CD20 22
23 Cutaneous T-cell LH diffuse CD4 CD8 Cutaneous T-cell LH bug bite Cutaneous T-cell LH bug bite 23
24 Cutaneous T-cell LH bug bite Cutaneous T-cell LH - diffuse Cutaneous T-cell LH - diffuse DIAGNOSIS: T-CELL LH, SECONDARY TO TATTOO REACTION 24
25 Tattoo CLH Courtesy of Dr. M. Tetzlaff CLH, Infections and Infestations HSV VZV Molluscum Contagiosum HIV Eosinophilic folliculitis Actinic reticuloid Often lots of plasma cells in biopsies Orf B. Burgdorferi Syphilis Dermatophytes Scabies Large cells 25
26 Too big!! CD30 I M SCARED! Pseudolymphoma DIAGNOSIS: MOLLUSCUM CONTAGIOSUM 26
27 Dermatophyte infection Am J Dermatopathol 2010 What s next Viral pseudolymphoma DIAGNOSIS: HSV INFECTION 27
28 Oh no!!! It s Hodgkin!!!! CMV infection 28
29 One last Orf, orf! Don t scratch 29
30 If I were you, I wouldn t do a CD30 Scabies Time for your medicine 30
31 Rash after dilantin administration D2-40 CD30 Atypical lymphoid hyperplasias In reality, ALH represents a basket category; a dysplastic nevus term to formulate a possible pre-lymphoma a.k.a. lymphoma in-situ Why not? Nihal et al coined the term to describe reactive lymphoid hyperplasias with clonal population of T or B-cells. ++ Solitary 30% TCR+ 27% IGH+ 4% both TCR and IGH Subset develop lymphoma Atypical marginal zone hyperplasia 6 cases affecting the tonsils and appendix of children Diagnosed as MALT lymphoma Lambda restriction Polyclonal results by PCR testing Guitart et al 2 cases on the skin Lymphomatoid keratosis BLK with lymphomatoid features years cm in size ALL SOLITARY scaly plaques, typically in the face Histologically identical to MF But lots of B-cells, normal CD4:CD8 ratio 10-20% TCR+ 31
32 ALH Courtesy of Dr. C. Scott ALH ALH 32
33 ALH ALH ALH CD3 CD20 33
34 ALH BCL-6 BCL-2 ALH IgG4 IgG ALH IgG4 Ki67 34
35 ALH Kappa Lambda Clonality assays 10-20% of CLH of T-cells have a positive clonality study 34% of CLH of B-cells have a positive clonality study The use of TCR assays in 2 separate biopsies showing identical clones has a specificity of >95% for diagnosis IGH only positive in 70-75% of CBCLs How about interobserver agreement Monoclonal IGH nearly 100% Indeterminate 60% Monoclonal TCR 68-97% Indeterminate 37% High throughput sequencing will improve the reliability of the assay MRD monitoring Costly (about 3 times the normal cost for BIOMED) Inflammatory dermatosis that could mimic lymphoma Actinic reticuloid (chronic actinic dermatitis) Pityriasis lichenoides Lupus erythematosus Morphea Perniosis Jessner s lymphocytic infiltrate 35
36 Actinic reticuloid Chronic eczematous photodermatosis lasting >3 months More common in HIV and men >60 Sensitivity to UVA, UVB, and visible light by patch testing is diagnostic Affects sun-exposed areas, particularly head and neck Histopathology Eczematous changes: parakeratosis, acanthosis, spongiosis, marked fibroplasia Brisk lymphocytic infiltrate with PREDOMINANCE OF CD8+ CELLS Actinic reticuloid Actinic reticuloid 36
37 Problem Case Problem Case Problem Case 37
38 Problem Case Problem Case Problem Case 38
39 Problem Case Problem Case CD3 CD7 Problem Case CD4 CD8 39
40 Pityriasis lichenoides Benign, self limited skin eruption composed of discrete red-brown scaly papules Darker skinned hypopigmented Weeks to months PLEVA/PLC part of the same spectrum Lesions in all stages of development Histopathology Interface and lichenoid dermatitis Dense perivascular inflammation and extravasated red blood cells PLEVA epidermal necrosis PLEVA: CD8+ PLC: CD4+ Recently 4/23 cases with gamma-delta phenotype Magro found 33/35 cases TCR+ PLC PLC 40
41 PLEVA PLEVA CD3 CD56 TCR-G J Cut Pathol
42 SPTCL and Lupus SPTCL and Lupus SPTCL and Lupus 42
43 SPTCL and Lupus SPTCL and Lupus CD4 CD8 SPTCL and Lupus CD3 CD7 43
44 SPTCL and Lupus TIA-1 GRANZYME Tumid lupus Erythematous dermal papules and plaques on trunk and face Photosensitivity 10-20% have +ANA Histopathology: Superficial and deep perivascular and periadnexal infiltrate with marked increased dermal mucin Lacks interface changes Overlap with Jessner s infiltrate Tumid Lupus 44
45 Perniosis Morphea Morphea 45
46 Folliculitis Folliculitis Folliculitis 46
47 Folliculitis? CD3 CD20 Folliculitis? CD10 BCL-6 Folliculitis? BCL-2 Ki67 FINAL DIAGNOSIS: COEXISTENT FOLLICULITIS AND PCFCL 47
48 Non-lymphoid lesions Merkel cell carcinoma Lymphoepithelial carcinoma Ewing s / PNET Small cell melanoma Cutaneous lymphadenoma Histiocytosis (Langerhan s and Non-Langerhan s cell) Leukemic deposits Mastocytosis Granuloma faciale Inflammatory pseudotumor Intralymphatic histiocytosis Lymphoepithelial carcinoma Lymphoepithelial carcinoma CD45 AE1/AE3 48
49 Small cell melanoma Ewing s / PNET Ewing s / PNET CD99 49
50 Cutaneous lymphadenoma Spiradenoma Epithelioid hemangioma 50
51 Epithelioid hemangioma Angiosarcoma Angiomatoid fibrous histiocytoma 51
52 Merkel Cell Carcinoma Merkel Cell Carcinoma Merkel Cell Carcinoma 52
53 Merkel Cell Carcinoma PAX5 CK20 OK, so now you re ready 53
54 54
55 IHC CD30 CD15 CD20 CD45 FINAL DIAGNOSIS: HODGKIN LYMPHOMA Thank you for your attention! 55
56 Hematopathology of the S,kin, Clinical & Pathological.Approach Alejandro A.Gru AndrasSchaffer WoltersKluwer 56
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