1/14/2018. Objectives
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1 2018 Pathology CME Cutaneous Hematopathology Maui, HI Jan 18 th 26 th Updates in Cutaneous B-cell Lymphomas 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 findings in common Cutaneous B-cell lymphomas (CBCL) Introduce prospective changes to the WHO classification of skin lymphomas Understand common clinical and histopathologic findings in rare types of CBCL Use of molecular and ancillary techniques that can help in the differential between cutaneous lymphomas and reactive infiltrates 1
2 Cutaneous B-cell lymphomas Primary cutaneous follicle center lymphoma Cutaneous marginal zone lymphoma (MALT lymphoma) Primary cutaneous diffuse large B-cell lymphoma, leg type Rare subtypes: Intravascular large B-cell lymphoma EBV+ diffuse large B-cell lymphoma EBV+ mucocutaneous ulcer Lymphomatoid granulomatosis Systemic B-cell lymphomas Some of them have frequent cutaneous dissemination CLL/SLL Mantle cell lymphoma Plasma cell neoplasms Plasmablastic lymphoma Follicular lymphoma Subtype Location / Clinical Age Morphology Immunophenotype Molecular Primary cutaneous follicle center lymphoma (PCFCL) Head and neck, trunk (plaques, papules, nodules, tumors) 55 median Nodular, diffuse, nodular anddiffuse Centrocytes, centroblasts and spindle cells CD20+, BCL6+, CD10-/+ (+ in nodular pattern more frequently), BCL2-/+ MUM1-, p63- CD21+ in follicles t(14;18) IGH-BCL2 (10-20%) 1p36del Diffuse large B-cell lymphoma, leg type (DLBCL-LT) Legs (10-20% outside this location; nodules and tumors +/- ulceration 76 median Diffuse Immunoblasts CD20+, BCL-6+, MUM1+, p63+, CD10- MYD88 mutations BCL6 translocations; BCL2 amplifications 9p21.3 deletion (loss of CDKN2A and CDKN2B ) Primary cutaneous marginal zone lymphoma (PCZML) Trunk and extremities (papulonodular rash) 55 median Nodular or diffuse Presence of GCs, monocytoid cells, plasma cells, centrocyte-like cells CD20+, CD10-, BCL-6-, CD43-, IgG or IgM, CD5-, intact or disrupted FDC, CD138 (if PCs), IgG4+ t(14;18) IGH-MALT1 Intravascular large B- cell lymphoma (IVLBCL) Trunk and extremities (macules, nodules, and plaques) 67 median Intravascular immunoblasts Western variant (++ skin) vs Asian variant (++hemophagocytosis) CD20+, MUM1+, BCL6+/-, CD5+/-, BCL- 2+ None specific Plasmablastic lymphoma (PBL) Oral cavity (tumor) and skin (in HIV), second peak (no HIV) Plasmablasts CD20 and CD19-, CD138+, CD79a+, EMA+, CD30+, CD10- /+, CD56-/+ MYC rearrangements (30-40%) EBER+ EBV-mucocutaneous ulcer (EBV-MCU) Oropharyngeal mucosa, perianal skin (ulcers) 77 median Diffuse Immunoblasts, RS cells, RS variants, necrosis. PAX5+, OCT2+, MUM1+, CD45+/-, CD30+, CD15+/-, CD20+/- EBER+ 2
3 Subtype Location / Clinical Age Morphology Immunophenotype Molecular Chronic lymphocytic leukemia (CLL) Head and neck (papules, plaques, nodules and tumors) 60 median Perivascular and periadnexal nodular and diffuse infiltrate of small lymphocytes. Rare Richter s transformation CD19+,CD20+, CD5+, CD23+,BCL-1-,CD43+ Trisomy 12 (30%), deletion 13q14 (25-50%), deletion 11q23 (10-20%) Mantle cell lymphoma Trunk, head and neck, 60 extremities (nodules and tumors) Nodular or nodular and diffuse. Small to medium sized lymphocytes. Blastoid and pleomorphic variants more frequent. CD19+,CD20+,CD5+,CD 43+,BCL1+,SOX11+,CD 23-,MUM1+ t(11;14) IGH-CCND1 Diffuse large B-cell lymphoma Variable, trunk and extremities more common (nodules and tumors, +/-ulceration) Variable, typically EBV-DLBCL Diffuse infiltrate of large cells. Geographic necrosis (EBVassociated) Immunoblasts; Hodgkin-like cells (EBV); plasmablasts CD19+,CD20+,CD5+/- (association with extranodal disease); CD30+/- Different groups ABC (MUM1+) vs GCT(CD10+ or BCL6+/MUM1-) Variable MYC, BCL2 and BCL6 translocations EBER: plasmablastic and EBV-DLBCL HHV8: effusion lymphoma ALK rearrangements Lymphomatoid granulomatosis Variable, trunk and extremities (nodules and tumors, -/+ ulceration) Angiocentric +/- angiodestruction, lymphohistiocytic panniculitis Immunoblasts, Hodgkin-like cells CD19+,CD20+,CD30+,E BER used for grading,cd15- EBER Plasma cell myeloma Trunk and extremities (nodules, tumors and plaques) very advanced stage 59 median Diffuse; +/- amyloid Malignant plasma cells and plasmablasts more frequent CD20,CD138+,CD38+,E MA+/-,CD56+,BCL1+/- deletion of 13q,17p- /p53 deletion or translocations t(4;14) and t(14;16) Primary cutaneous follicle center lymphoma (PCFCL) Indolent B-cell lymphoma with germinal center differentiation Most frequent CBCL 1/3 to 1/2 of CBCLs By definition, limited to the skin Initial staging of patients include careful exam, laboratories and radiologic studies (PET-CT, CT) Adults: (median 51-58); slight male predominance Etiology: unknown, minority associated with B. Burgdorferi; HCV; HHV-8 Clinical presentation: Solitary or clustered Erythematous to violaceous infiltrated papules, plaques, nodules/tumors Ulceration is not common More frequently in the head and neck: scalp Crosti s lymphoma (reticulohistiocytoma of the dorsum): figurate, annular erythematous plaques in the back Some can mimic rosacea, insect bites and folliculitis 5 year survival >95%; recurrence 20-50% PCFCL 3
4 PCFCL Histopathologic findings: Mixture of centrocytes and centroblasts Patterns Follicular Follicular and diffuse Diffuse Epidermis is spared grenz zone Grading IS NOT reflective of behavior Follicular pattern: distorted, variable sized follicles in dermis and subcutis with lack of tingible body macrophages Absent mantle zone Lack of polarization Diffuse pattern: more frequent Sheet-like growth Variable centroblasts Spindle cell type: Crosti s lymphoma PCFCL, nodular pattern PCFCL 4
5 PCFCL CD20 CD3 PCFCL CD10 BCL-2 PCFCL CD23 Ki67 5
6 PCFCL, diffuse pattern PCFCL PCFCL CD3 CD20 6
7 PCFCL CD10 BCL-2 PCFCL, spindle cell variant (Crosti s lymphoma) PCFCL 7
8 PCFCL BCL-6 CD20 PCFCL - Immunophenotype Expression of pan B-cell antigens CD20, PAX-5, CD79a, CD19 Germinal center markers CD10+/-: more common in follicular, less in diffuse BCL-6 GCET Follicular dendritic networks: CD21/CD23 Proliferation index (Ki67): Normal follicles: >95% Neoplastic follicles: <50% BCL-2-, but present in 20-25% MUM1-,IgM and IgD-, p63- Clonality: IHC, ISH, IGH PCFCL, BCL-2+ 8
9 PCFCL, IHC CD20 CD3 PCFCL, IHC BCL-6 BCL-2 PCFCL - ISH KAPPA LAMBDA 9
10 PCFCL Molecular findings IGH-BCL2 t(14;18) is typical of systemic FL Present in 8-41% of PCFCL Do not use to distinguish from systemic FL Minority of cases BCL-6, BCL-2 and MALT1 Some cases 1p36del PCFCL Primary Cutaneous Follicle Center Lymphomas Expressing BCL2 Protein Frequently Harbor BCL2 Gene Break and May Present 1p36 Deletion: A Study of 20 Cases. Szablewski, Vanessa; Ingen-Housz-Oro, Saskia; Baia, Maryse; Delfau-Larue, Marie-Helene; MD, PhD; Copie- Bergman, Christiane; MD, PhD; Ortonne, Nicolas; MD, PhD American Journal of Surgical Pathology. 40(1): , January DOI: /PAS FIGURE 3. FISH results for BCL2 and 1p36. A, PCFCL showing BCL2 rearrangement using a break-apart probe, with isolated green and red signals (arrows) in most cells. B, PCFCL with BCL2 rearrangement and amplification (arrow). C and D, In this PCFCL, a del 1p36 is seen with unique red signals (1p36)(arrows), whereas 2 green signals (1q25 control) are observed in tumor cell nuclei. Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.published by Lippincott Williams & Wilkins, Inc. 2 PCFCL Differential Diagnosis Cutaneous lymphoid hyperplasia Cutaneous marginal zone lymphoma Sometimes very difficult Presence of atrophic GCs Primary cutaneous DLBCL, leg type Very frequent to find very large number of centroblasts in PCFCL!!! P63, MUM-1, CD10-, IgM and IgD Systemic follicular lymphoma 10
11 The location of CBCL is REALLY important J Clin Oncol 2007 Primary cutaneous marginal zone lymphoma (PCMZL) In 2005 WHO-EORTC cutaneous MALT was listed as a separate entity 2008 WHO cutaneous MALT was included under systemic MALTs SALT (skin-associated lymphoid tissue) Primary cutaneous immunocytoma Primary cutaneous plasmacytoma Low-grade B-cell lymphomas of the skin. 7% of all CL; 20-40% of CBCLs Median age 55 Most common CBCL in children Men to women 2:1 Etiology: Unknown Chronic antigenic stimulation! IgG (80-90%) vs IgM (10-20%) B. burgdorferi in Europe ONLY Clinical features: Solitary or multiple red to violaceous papules, nodules or plaques Trunk, upper extremities, head and neck 50% cutaneous relapses 11
12 PCMZL PCMZL Anetodermic forms PCMZL - Histopathology Nodular or diffuse growth pattern in the dermis, subcutis Lack of epidermal involvement (rare cases of epidermotropic MZL) Periadnexal tracking of the malignant infiltrate (eccrine glands and hair follicles) is typical Admixed atrophic GCs are frequent Polymorphous infiltrate: Monocytoid B-cells, plasma cells, lymphoplasmacytic cells Background rich in T-cells (IgG) or B-cells (IgM) Sometimes extreme plasma cell differentiation Scattered background eosinophils 12
13 PCMZL PCMZL PCMZL 13
14 PCMZL, atrophic GCs PCMZL PCMZL 14
15 PCMZL PCMZL PCMZL, IHC CD3 CD20 15
16 PCZML KAPPA LAMBDA PCMZL PCMZL 16
17 PCMZL PCMZL CD20 CD3 PCMZL BCL-6 CD10 17
18 PCMZL KAPPA LAMBDA PCMZL, EPIDERMOTROPISM CD20 CD79a 18
19 PCZML, blastoid variant PCMZL, interstitial pattern PCMZL, interstitial pattern 19
20 PCMZL, interstitial pattern PCMZL, IHC CD19 CD3 PCMZL, IHC CD20 CD10 20
21 PCMZL, IHC BCL-2 CD138 PCMZL, ISH KAPPA/LAMBDA PCMZL - Immunophenotype Expression of pan B-cell antigens: CD20, CD19, CD79a, PAX-5 (less if rich plasma cell population) CD5-, CD10-, BCL-6-, CD23-,Cyclin D1- Plasma cells: CD138+, CD38+, CD79a+, CD20-, IgG4+ GCs: BCL-6 and CD10+, BCL-2-, Ki67>90% Dendritic networks: irregular and expanded (CD21) Blastoid variant could be CD5+ 21
22 Class switched in most cases Predominance of T-cells Mast cells IgG Lack extracutaneous involvement Frequent IgG4+ plasma cells Debate whether lymphoma vs reactive process with monotypic plasma cells Analogous to lambdarestricted PCs proliferations in the tonsils of children Non-class switched Predominance of B-cells (diffuse proliferation) IgM 50% have extracutaneous disease More similar to systemic MALT lymphomas Rare (<10% of cases) Cutaneous Marginal Zone Lymphomas Have Distinctive Features and Include 2 Subsets. Edinger, James; Kant, Jeffrey; MD, PhD; Swerdlow, Steven American Journal of Surgical Pathology. 34(12): , December DOI: /PAS.0b013e3181f72835 FIGURE 2. Class-switched CMZL (case 12). A, Note the dense dermal nodules with predominantly small lymphoid cells and 1 distinct follicle with a germinal center. B, A CD20 stain highlights the follicle and occasional other positive aggregates but otherwise, shows only scattered positive cells. C, There are numerous CD3+ cells outside of the follicle. D, CXCR3 is expressed on many T cells but is negative in the B cell aggregates. E, ([kappa]), (F) ([lambda]). Note the focally marked predominance of [lambda] light chain-restricted plasma cells. G, (IgG), (H) (IgM). Most plasma cells are IgG+ and IgM-. A, hematoxylin and eosin, (B-H) immunoperoxidase with hematoxylin counterstain. 2010LippincottWilliams & Wilkins, Inc. Publishedby LippincottWilliams & Wilkins, Inc. 2 Cutaneous Marginal Zone Lymphomas Have Distinctive Features and Include 2 Subsets. Edinger, James; Kant, Jeffrey; MD, PhD; Swerdlow, Steven American Journal of Surgical Pathology. 34(12): , December DOI: /PAS.0b013e3181f72835 FIGURE 3. Nonclass-switched CMZL (case 27). A, Note the dense diffuse dermal small lymphoid infiltrate. B, A CD20 stain shows extensive diffuse positivity. C, There are still moderately numerous admixed CD3+ T cells. D, CXCR3 is diffusely positive with apparent stronger staining of T cells and weaker staining of many B cells. E, ([kappa]), (F) ([lambda]). There is a marked predominance of [lambda] light chain-restricted plasma cells plus weak [lambda] staining on many B cells. G, (IgG), (H) (IgM). The IgM stain shows a similar pattern to [lambda] while there are only rare IgG+ cells. A, hematoxylin and eosin, (B-H) immunoperoxidase with hematoxylin counterstain. 2010LippincottWilliams & Wilkins, Inc. Publishedby LippincottWilliams & Wilkins, Inc. 2 22
23 PCMZL Genetic findings t(14;18)(q32;q21) IGH and MALT1 25% t(3;14)(p14;q32) IGH and FOXP1 t(11;18)(q21;q21) AP12/MALT1 Very rare: more common in MALTs from the lung and GI tract PCMZL Differential diagnosis Cutaneous lymphoid hyperplasia Typically negative IGH gene rearrangement Reactive GCs as opposed to atrophic GCs Small to medium sized CD4+ LPD Clonal population of T-cells Expression of T FH markers Plasmacytoma Very rare on the skin When plasma cell neoplasms involve the skin, average 2-3kg of systemic disease CLL/SLL CD5+,CD23+ PCFCL can sometimes be very challenging! Primary cutaneous DLBCL, leg type Legs of elderly individuals Mean age: 77 Women to men 1.6: % of CBCLs Etiology: Unclear HHV-6, HHV-8 MTX Clinical features: Large tumors and nodules with or without ulceration Plaques 10-20% outside legs!!! Multiple lesions in most cases B symptoms in 10% of cases Common spread to extracutaneous sites 5-year survival 55% 23
24 DLBCL-LT A B C D DLBCL-LT DLBCL-LT - Histopathology Diffuse dermal infiltrate with extension into the adipose tissue, sparing of the epidermis Rare cases with epidermotropism Large areas of geographic necrosis Variable morphology: large cells with immunoblastic appearance; anaplastic; Burkittlike Immunophenotype: pan B-cell markers (CD19+,CD79a+,CD20+,PAX-5+) ABC type (CD10-,MUM1+,BCL-6+) BCL-2+ IgM and IgD+ p63+, MYC+ (55%) 24
25 DLBCL-LT DLBCL-LT DLBCL-LT 25
26 DLBCL-LT DLBCL-LT CD3 CD20 DLBCL-LT BCL-2 MUM1 26
27 DLBCL-LT, Ki67 DLBCL-LT ISH-KAPPA ISH-LAMBDA DLBCL-LT, epidermotropism 27
28 DLBCL-LT, epidermotropism DLBCL-LT, epidermotropism CD20 MUM1 DLBCL Hans algorithm Hans"Algorithm" +" GCT% CD10%( 30%)% CD10% +" ABC% #" BCL/6% ( 30%)% +" MUM1 % ( 30%)% #" GCT% MUM1% BCL/6% #" ABC% 28
29 DLBCL-LT molecular aspects JAMA Dermatol 2015 DLBCL-LT molecular aspects MYD88 mutations (>90%) CDKN2A (9p21) alterations (25%) Cases with loss p16 expression (43% vs 70% 5-year survival) Amplification of 18q21 BCL2 gene BCL-6 rearrangements (22%) MYC rearrangements BCL2 and MALT1 amplification in 67% DLBCL-LT vs 11% PCFCL (13%) BCL11A and c-rel amplification is more common in PCFCL DLBCL-LT differential diagnosis Cutaneous and systemic B-cell lymphomas PCFCL Location, location, location Germinal center phenotype p63, MUM1 negative Intravascular large B-cell lymphoma Also ABC Sometimes CD5+ Pure intravascular location Lymphomas with plasmablastic appearance Plasmablastic lymphoma Primary effussion lymphoma ALK+ DLBCL Burkitt lymphoma EBV+ DLBCL 29
30 PCFCL vs DLBCL-LT Am J Surg Pathol 2010 PCFCL vs DLBCL-LT 21/30 cases of DLBCL- LT vs 4/35 cases of PCFCL show strong and diffuse expression of p63 Why is it important? DLBCL-LT: R-CHOP +/- XRT PCFCL: Local therapy, R only if recurrence or multiple lesions Robson A. Histopathology 2016 PCFCL transformed to DLBCL 30
31 PCFCL transformed to DLBCL PCFCL transformed to DLBCL PCFCL transformed to DLBCL CD20 CD20 31
32 PCFCL transformed to DLBCL BCL-2 BCL-6 PCFCL transformed to DLBCL MUM1 KI67 DLBCL, special types with frequent cutaneous presentation Plasmablastic lymphoma ALK+DLBCL EBV+DLBCL High-grade CD10+ DLBCLs Including double and triple hit lymphomas Intravascular large cell lymphomas Lymphomatoid granulomatosis CD5+DLCBL Primary effusion lymphoma (PEL) 32
33 Plasmablastic lymphoma Most cases in the oral cavity and associated with HIV Also immune-supression, elderly, transplant Nodules and tumors, solitary or multiple Histopathology Plasmablasts (immunoblastic cells with eccentric nuclei, large prominent central nucleoli) Starry-sky pattern similar to BL Immunophenotype PC markers: CD138, CD79a, CD38 CD30+, EMA+, CD10+ Ki67>90%, variable CD56 B-cell markers are NEGATIVE EBER+ Molecular: rearrangement or amplification of MYC in 45% PBL PBL 33
34 PBL - Immunophenotype CD138 CD56 PBL - Immunophenotype Ki67 EMA EBV+ DLBCL Formerly EBV+ DLBCL of the elderly More common in Asia and Mexico Less frequent in Western countries Striking predilection for extranodal sites (70%) Skin, lung, tonsils and stomach 20-30% of BCL in individuals >90 years Cutaneous plaques and tumors Histopathology Polymorphous variant: mixture of immunoblasts, plasmablasts, centroblasts, and the presence of cells with Hodgkin or Hodgkin-like appearance Monomorphous variant: sheets of immunoblasts Geographic necrosis Immunophenotype Pan B-cell markers: CD20, CD19, CD79a, PAX5 Non-germinal center phenotype MUM1+, BCL-6+/-, CD10- CD30 positive EBV+ Median survival 2 years 34
35 EBV+DLBCL EBV+DLBCL EBV+DLBCL 35
36 EBV+DLBCL CD20 CD3 EBV+DLBCL PAX-5 BCL-6 EBV+DLBCL CD30 Ki67 36
37 EBV+DLBCL Intravascular large B-cell lymphoma Very rare lymphoma subtype 2Variants Western form: higher prevalence of skin disease, younger age and more indolent clinical course 26% skin limited disease Asian form: more aggressive, less skin involvement, frequent association with hemophagocytosis Advanced age: median 67 15% of cases have a preceding NHL Survival: 56% at 3 years (skin); 22% in disseminated cases Symptoms: B-symptoms 55% Skin manifestations: nodules and/or plaques (49%) or macules (22.5%) of red (31%) or blue to livid (19%) color on the leg (35%), the thigh (41%), and the trunk (31%). Histopathology: Multiple skin biopsies are needed!! Lymphoma cells are confined to vascular spaces Fibrin thrombi and ischemic changes are also common Large lymphoma cells with immunoblastic features Immunophenotype: GC (20%) vs NGC (80%) CD20+, CD79a+, MUM1+, BCL-2+ CD5+ (40%) Cyclin D1- IVLCL 37
38 IVLCL IVLCL IVLCL 38
39 IVLCL IVLCL CD20 Ki67 Lymphomatoid granulomatosis (LyG) Immunophenotype EBV+ Grading: Grade 1: <5 EBER+ cells Grade 2: 5 20 EBER+ cells Grade 3: >50 EBER+ cells CD30+, CD20+ Rare angiocentric and angiodestructive process associated with EBV infection Clinical: Respiratory symptoms are very common (lung involvement) Skin involvement in 40-50% of cases (nodules and ulcers) Other organs: kidney, CNS, Gi tract B symptoms 80% Histopathology: Lymphohistiocytic infiltrate with perivascular and periadnexal distribution Lymphohistiocytic panniculitis with granulomatous features Angiocentric infiltrate with large pleomorphic cells with RS-like appearance 39
40 Lymphomatoid granulomatosis Lymphomatoid granulomatosis Lymphomatoid granulomatosis CD20 EBER 40
41 LyG High grade CD10+ BCL Previous grey-zone category or Burkitt-like lymphoma 4% of high-grade B-cell lymphomas Magroetalreported3cases of double-hit lymphomas on the skin 1 triple-hit case Genes involved: MYC, IGH- BCL2, BCL-6 Morphology: at least areas with BL appearance (starrysky) IHC: CD20+, MYC+, CD10+, Ki67 >90%, BCL-2+, BCL-6+ Swerdlow et al. Blood 2016 Double-hit lymphoma 41
42 Double-hit lymphoma Double-hit lymphoma Double-hit lymphoma CD20 BCL-6 42
43 Double-hit lymphoma BCL-2 Ki67 Double-hit lymphoma ALK+ DLBCL 43
44 ALK+ DLBCL PAX-5 ALK+ Primary effusion lymphoma Rare NHL associated with HHV-8 4% of NHL in HIV+ Tumors with plasmablastic appearance Frequent intravascular dissemination Skin PEL 44
45 CD5+ DLBCL 5-10% of DLBCL are CD5+ Advanced stage and frequent extranodal involvement (75% cases) Centroblastic or immunoblastic appearance Occasional IV involvement IHC: CD5+, MUM1+, BCL- 6+ Distinguish from Richter s transformation!!!! Differential diagnosis CLL/SLL with transformation IVLCL Mantle cell lymphoma, pleomorphic or blastoid variants CD5+ DLBCL CD5+ DLBCL 45
46 CD5+ DLBCL CD20 CD5 Richter s transformation in CLL CD5 Courtesy of Dr. M. Pulitzer Cutaneous Mantle cell lymphoma Almosts always systemic, but rare primary cases described Usually advanced stage when cutaneous involvement IHC; CD5+, Cyclin D1+, t(11;14) or variants In the skin, higher prevalence of blastoid and pleomorphic variants Blastoid: >20-30 mit/10 hpf 46
47 Cutaneous MCL Cutaneous MCL Cutaneous MCL PAX-5 CD5 47
48 Cutaneous MCL Ki67 Cyclin D1 EBV+ B-cell LPD EBV+ mucocutaneous ulcer (EBV-MCU) EBV-associated PTLD Methotrexate-associated LPD EBV-MCU EBV-MCU is a solitary, sharply demarcated ulcerated lesion in the skin, oral cavity, or GI tract Iatrogenic or age-related immune supression Azathioprine, cyclosporine, MTX Allo BMT Isolated regional LAD can occur Spontaneous resolution in 25% Histopathology: Shallow mucosal or cutaneous ulcer, +/- pseudoepitheliomatous changes Polymorphous infiltrate that includes mixture of lymphocytes, plasma cells, histiocytes, immunoblasts and RS-like cells Necrosis+++ IHC: PAX-5+, OCT2+, MUM1+, CD45+/- CD30+, CD15+ (40%) EBV+++ Clonal T and B-cells 48
49 EBV-MCU Am J Surg Pathol 2010 EBV-MCU EBV-MCU 49
50 EBV-MCU EBV-MCU PAX-5 CD20 EBV-MCU CD30 CD15 50
51 EBV-MCU CD45 CD163 Cutaneous PTLD Most PTLDs in the skin are of T-cell type Most B-PTLD are EBV+, but only 10-20% of T-PTLD are associated with EBV 22% of PTLD show cutaneous involvement B-PTLD DLBCL Plasmacytoma Rarerely PBL or LyG T-PTLD C-ALCL MF Cutaneous PTCL Cutaneous PTLD - DLBCL 51
52 Cutaneous PTLD - DLBCL CD20 EBER MTX-related lymphoid proliferations Am J Surg Pathol 2014 Patients on chronic MTX therapy Cutaneous MTX-LPD is rare Tumors or plaques on the lower extremities with ulceration DLBCL or SPTCL Spontaneous regression upon discontinuation of MTX!!! Elderly (mean 76) >4 years of treatment, RA and other CTDs Histopathology: DLBCL, HLlike, SPTCL, LyG MTX-LPD 52
53 Thank you for your attention! Hematopathology of the S,kin, Clinical & Pathological.Approach Alejandro A.Gru AndrasSchaffer WoltersKluwer 53
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