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Cutaneous pseudolymphoma
- 1. Cutaneous PSEUDO-lymphoma Moderator –Prof Uma Nahar
- 2. Outline of presentation •Pattern of B and T cell infiltration • Define Cutaneous pseudolymphoma • Classification • Subtypes • Important entities with clinico-pathological features • Differential features from morphologically similar lesions • Pseudoclonality
- 3. Comparison of Tcell and B cell pattern in skin T – cell B – cell Scaling plaques and patches Band like Plum-like nodule Nodular infiltrate Perivascular infiltrate Epidermal involvement Vascular, subcutis and interstitial infiltration
- 4. Comparison of Tcell and B cell pattern in skin T cell B cell Band like architecture Nodular architecture Perivascular infiltrate Perivascular and periadnexal infiltrate Epidermal involvement present (Exocytosis, epidermotrophism and folliculotrophism) Epidermal involvement absent Grenz zone absent Grenz zone present Lever’s histopathology of skin 11th Edn
- 5. Definition • Cutaneous Pseudolymphoma “Aheterogeneous group of skin lesions having lymphocyte-rich infiltrate, simulating clinically and/or histologically cutaneous lymphoma” Surg Path Clinics (10) 2017, 455-476
- 6. Most important ingredientfor diagnosis Clinicopathological co-relation
- 7. Causes of pseudolymhpoma Infectiousagents • Spirochetal bacteria • Virus • Parasites Foreign agents • Tattoo dyes • Injection vaccination • Piercing Others • Insect bites • Drugs • Photosensitivity Surg Path Clinics (10) 2017, 455-476
- 8. Clinical presentation Nodule Clusteredpapules Disseminated papules Erythroderma Surg Path Clinics (10) 2017, 455-476
- 9. Groups Nodular Pseudo- mycosis fungoides Intravascular Others Surg PathClinics (10) 2017, 455-476
- 10.
- 11. Nodular pseudolymphoma Most commontype Solitary or multiple nodules Classified as T-cell, B-cell or mixed
- 12. Cutaneous B cellpseudolymphoma (Clinical characteristics) • Syn: Lymphocytoma cutis or cutaneous lymphoid hyperplasia • Gross • Solitary nodule (most common) • M: F :: 3:1 • <40 yrs, rare in children (<10%) Am J Dermatopathol 2004 (26), 4–13
- 13. Solitary Nodule Nodular infiltratein the dermis and superficial parts of subcutis Small B cells, no nuclear atypia Prominent germinal centers Bcl6 positive Bcl2 negative CD21
- 14. Cutaneous B cellpseudolymphoma (Summary) Histologic Characteristics Immunohistochemistry Nodular infiltrate in the dermis and superficial parts of subcutis Small B cells, no nuclear atypia CD5(-), CD20(+), CD23 (-), CD43(-) Reactive germinal centers Follicle centers: Bcl2(-), Bcl6(+). Well defined and regular structured networks of CD21(+) FDCs, elevated Ki-67 rate mostly confined to the germinal centers Tingible body macrophages CD68(+) Scattered plasma cells CD79a(+), CD138(+), no light chain restriction (kappa, lambda) Sometimes eosinophils Admixed T cells at variable degree (commonly <30%) CD3(+), CD4(+), and CD8(+) Small clusters of plasmacytoid dendritic cells CD123(+)
- 15. Cutaneous B cellpseudolymphoma (Differential diagnosis) Cutaneous B cell pseudolymphoma Primary cutaneous marginal zone lymphoma Primary cutaneous follicle center lymphoma
- 16. Cutaneous B cellpseudolymphoma (Differential diagnosis) B-Cell Pseudolymphoma Primary Cutaneous Marginal Zone Lymphoma Primary Cutaneous Follicle Center Lymphoma Gender (female:male) 3:1 1:2 1:1.5 Age (y) 75% < 40 55 51 Localization Face > upper trunk > arms Upper trunk > upper arms > face/head Head/face > upper trunk Histology Dermal/superficial subcutis, reactive germinal centers, tingible body macrophages, scattered plasma cells Dermal/superficial subcutis, reactive germinal centers can be found, plasma cells in the periphery of the infiltrates and near by the epidermis Dermal/superficial subcutis, neoplastic irregular germinal centers of different size (CAVEAT: not found in diffuse type)
- 17. Cutaneous B cellpseudolymphoma (Differential diagnosis) B-Cell Pseudolymphoma Primary Cutaneous Marginal Zone Lymphoma Primary Cutaneous Follicle Center Lymphoma Immunohistochemistry CD20+; reactive germinal centers (Bcl-2-, Bcl-6+); high proliferative activity in geminal centers (Ki-67 +), sharply restricted networks of FDCs (CD21+) Tumor cells: CD20+ Bcl-2+; Bcl-6-, CD5-, CD10-,CD43-; reactive germinal centers (Bcl- 2-, Bcl-6+) Tumor cells: CD20+, Bcl-6+; Bcl-2-(90%); neoplastic germinal centers (Bcl-2-,Bcl-6+); proliferating cells (Ki-67+) are scattered; irregular networks of FDCs (CD21+) Molecular diagnostics Polytypic light chains, polyclonal IgH Monoclonal IgH (up to 90%) Monotypic light chain (85%) monoclonal IgH (60%–70%)
- 18. Borrelia-associated B-cell pseudolymphoma Syn: Lymphocytomacutis; lymphadenosis cutis benigna History of tick bite and localization at predilection site (Earlobes, nipple, scrotum) Borrelia burgdorferi - Serology; DNA PCR J Cutan Pathol 2004 (31), 232–40
- 19. Blue Nodule Dense dermalnodular infiltrate with reactive germinal centers with small or completely lost mantle zones Germinal centers with multiple tingible body macrophages
- 20. Borrelia-associated B-cell pseudolymphoma Mostly theentire dermis is involved Grenz zone, epidermal component in approx 10% High number of admixed T cells Germinal centers (77%), often large and confluent Absence of mantle zone (88%) Tingible body macrophages (100%) Plasma cells (99%) Eosinophils (84%)
- 22. Cutaneous T-cell pseudolymphomaand mixed pseudolymphoma Nodular T-PSL : dense dermal T-cell–rich nodular infiltrate, accompanied by variable number of B cells, (up to 30%) Mixed forms of PSL: Equal number of T cells and B cells All causes identified in B-PSL can also be found as underlying stimuli in T-PSL and mixed PSL. Surg Path Clinics (10) 2017, 455-476
- 23. Solitary red flatnodule on the forehead CD4 expression in a majority of the small lymphocytes Variable number of slightly enlarged lymphocytes with chromatin dense nuclei Dense nodular wedge shaped infiltrate in the entire dermis
- 24. Cutanoeus T-cell pseudolymphoma Nodularinfiltrate in the entire dermis Predominantly small lymphocytes with dense chromatin Variable number of eosinophils, histiocytes, & plasma cells B cells in small aggregates. Germinal centers are rare Exocytosis of hair follicle by T cells but not epidermis CD4 + predominance
- 25. Nodular CD4 +T cell Pseudolymphoma (Differential diagnosis) Nodular CD4+ T cell pseudolymphoma Tumor stage Mycosis Fungoides Angioimmunoblastic T- cell lymphoma Tumid lupus Dermatology 2009 (219), 42–7
- 26. Nodular CD4 +T cell Pseudolymphoma (Differential diagnosis) CD4 + small/medium sized T- cell lymphoma Mycosis Fungoides – tumor stage Infiltration by Angioimmunoblstic T cell Lymphoma Located on head and neck area with an indolent course MF in tumor stage medium- sized T-cells with atypia AITL has small CD4+ and PD-1+ T cells are accompanied by a significant number of B cells and histiocytes Cannot be distinguished from CD4+ T cell PSL – clinically, or by histologic and phenotypic features MF have monoclonal T-cell receptor (TCR) rearrangement AITL patients have B symptoms, serologic findings, nodal involvement Both considered as similar lesions with the term : Cutaneous CD4+ small/medium sized T-cell lymphoproliferative disorder (WHO 2016) Clinical presentation with patches and plaques preceding the tumors in MF AITL have high proliferation rate and associated with EBV Tumid Lupus : Mucin stains help distinguish
- 27. CD30+ T-cell pseudolymphoma Characterizedby medium to large atypical CD30+ T-cells Blastlike cells usually found as single units scattered in the infiltrate Causes include - • (Lymphomatoid) drug eruption • Nodular scabies J Cutan Pathol 2008 (35),1100–7.
- 28. Arthropod bite reactionwith a wedge shaped mixed infiltrate, spongiotic dermatitis, and papillary edema Infiltrate consists of lymphocytes, histiocytes, and eosinophils.A few (immuno-) blastlike cells are admixed Blastlike cells were positive for CD30
- 29. CD30+ T-cell pseudolymphoma AmJ Dermatopathol (35)2013, J Cutan Pathol (35) 2003 Lymphomatoid drug reaction Herpes simplex Molluscum contagiosum
- 30. CD30 + Tcell Pseudolymhoma (Differential diagnosis) CD30+ T cell pseudolymphoma Lymphomatoid papulosis Cutaneous anaplastic large cell lymphoma
- 31. CD30 + Tcell Pseudolymhoma (Differential diagnosis) Lymphomatoid papulosis (LYP) (in particular histologic type A) Cutaneous anaplastic large cell lymphoma (ALCL) Neoplastic Reactive Number of CD30+ cells Often higher number Lower number Arrangement Little clusters or sheets More scattered distribution as single units CD30 staining intensity Often more intensive Often weak Composition of infiltrate CD30+ LPD type A: mixed infiltrate with many histiocytes, ALCL: predominantly CD30+ cells arranged in sheets Higher number of admixed B cells and plasma cells
- 32.
- 33. Pseudo-mycosis fungoides Group ofdisorders of different etiology, which histologically mimic MF Clinicopathologic correlation is crucial to avoid misinterpretation May exhibit subtle nuclear atypia CD4+ or CD8 + with variable expression of CD30 Am J Dermatopathol 2013 (35), 343–50
- 34. Bandlike infiltrate ofmostly small lymphocytes with exocytosis into the epidermis. Many admixed eosinophils in the upper dermis
- 35. Pseudo-mycosis fungoides (Differential diagnosis) Differentialdiagnosis • MF and Sezary syndrome • Cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma • Primary cutaneous LYP Features favouring neoplasia • Profound nuclear atypia, • Predominance of medium- sized to large cells • Loss of pan T-cell markers • Monoclonal rearrangement of TCR genes
- 36. Pseudo-mycosis fungoides Lymphomatoid ContactDermatitis Lymphomatoid Drug Reaction Actinic Reticuloid CD8+ T-cell Pseudolymphoma in Immunodeficiency Borrelia-Associated Tcell Pseudolymphoma Papuloerythroderma of Ofuji
- 37. Lymphomatoid Contact Dermatitis Chroniccontact dermatitis Adults; M=F History of exposure of allergens Eczematous and pruritic papules, patches or plaques Superficial bandlike infiltrate, spongiosis, pseudo-Pautrier collections, eosinophils CD4 = CD8, Sometimes admixed larger CD30+ cells TCR mostly polyclonal Identification of allergen (patch test) Contact Dermatitis 1976 (2)139–43.
- 38. Scaly, erythematous patches CD8+T cell Inflammatory infiltrate of atypical lymphocytes in the superficial dermis with epidermotropism
- 39. Lymphomatoid Drug Reaction Adults Macularor papular eruptions CCBs, ACE inhibitors, antidepressants, antihistamines, beta- blockers, benzodiazepines, lipid- lowering agents Superficial, Bandlike infiltrate, eosinophils CD4 or CD8 predominance, Admixed CD30+ cells Caveat: loss of pan-T- cell markers is possible TCR mostly polyclonal Am J Dermatopathol 2013 (35), 343–50
- 40. Erythematous macules andpapules with fine to thick scale Lichenoid and perivascular lymphoid infiltrate associated with acanthosis, spongiosis, and scale crust Scattered CD30+ cells
- 41. Actinic Reticuloid Chronic multifactorial dermatitiswith severe photosensitivity Middle age and older men Face, neck In sun exposed areas: persistent erythematous lichenoid papules and plaques, facies leonina Psoriasiform hyperplasia, mild spongiosis, eosinophils, coarsed and vertically arranged collagen bundles in the papillary dermis CD8 + cells TCR mostly polyclonal Increased number of circulating CD8+ cells in the peripheral blood, photosensitivity Semin Diagn Pathol 1991 (8)109–16.
- 42. Ill-defined confluent lichenifiedplaques involving the face, neck, and extending into the torso. Acanthosis, parakeratosis, spongiosis, and prominent eosinophils CD8+ cells
- 43. CD8+ T-Cell Pseudolymphomain Immunodeficiency HIV with deep immunosuppression, other type of immunosupression Generalized Variable: plaques> erythroderma, palmoplantar hyperkeratosis, lymphadenopathy Superficial and mid- dermal infiltrate, no atypia CD8+, TIA-1, granzyme B TCR mostly polyclonal Clin Infect Dis 2010 (51) 741–8.
- 44. Dry, scaly andpruriginous erythroderma Parakeratosis and perivascular upper dermis infiltrate of small, regular lymphocytes with a slight subepidermal band and epidermotropism CD3 + and CD8+ cells
- 45. Borrelia Associated T-cell pseudolymphoma 60years Male + Female Lower limbs erythema chronicum migrans, acrodermatitis chronica atrophicans, MF like, lichenoid aspect Bandlike or deep, lichenoid aspect, lymphocytes, histiocytes (pseudorosettes), variable number of plasma cells CD4+ TCR mostly polyclonal Detection of Borrelia burgdorferi PCR, serology Am J Dermatopathol 2015 (37)715–8.
- 46. Multiple lichenoid red-brownishmaculae and flat papules on the back Superficial bandlike lymphocytic infiltrate The infiltrate predominately consists about T- lymphocytes with a few admixed plasma cells. Vacuolar alteration of the junctional zone
- 47. Papuloerythroderma of Ofuji 70years Male > Female Generalized, especially trunk and limbs Itchy flat topped red to brownish papules, erythoderma with (deck chair sign), palmoplantar hyperkeratosis, lymphadenopathy Pattern of chronic dermatitis with a variable epidermal hyperplasia with mild spongiosis and a mixed inflammatory infiltrate, predominately consist of lymphocytes, histiocytes and eosinophils CD4 = CD8 TCR mostly polyclonal Blood eosinophilia Acta Derm Venereol 2009 (89), 618–22.
- 48. Erythroderma Exocytosis. Perivascular and periadnexalinfiltrate. Lymphocytes, esoinophils and plasma cells
- 49.
- 50. Lymphocytic Infiltration ofthe Skin and Palpable Arciforme Migratory Erythema Assigned to the group of lupus erythematosus PAME: Infiltrated annular erythema developing into large migrating lesions (trunk) LIS: sharply demarked often symmetric infiltrated plaques (face) Dense perivascular and periadnexal predominantly lymphocytic infiltrate Pattern of chronic dermatitis with a variable epidermal hyperplasia with mild spongiosis Mixed inflammatory infiltrate, predominately consist of lymphocytes, histiocytes and eosinophils TCR mostly polyclonal J Am Acad Dermatol 2008 (58), 217–23.
- 51. Multiple erythematous plaques Heavychronic inflammatory cell infiltrate cuffs the vessels in the superficial and mid dermis CD4+ lymphocytes
- 52. Arciform erythemas onthe back Dense lymphocytic infiltration about vessels and appendages Predominantly of lymphocytes
- 53. Infections as Simulatorsof Lymphomas Cutaneous leishmaniasis Lymphocytes, histiocytes, and plasma cells Detection of the agents Herpes simplex virus and varicella zoster virus Without the pathognomonic epithelial changes (herpes incognito) Lymphocytes enlarged and atypical-appearing chromatin dense nuclei. CD30+ Detection of viral antigens by IHC and/or detection of viral DNA Parapoxvirus infections Cytomorphological changes and expression of CD30 by the infiltrating T cells Inclusion bodies, absence of loss of T-cell markers, lack of monoclonal rearrangement of TCR Surg Path Clinics (10) 2017, 455-476
- 54. Inflammatory Disorders asSimulators of T-Cell Lymphoma Lichen planus (6%) Lichen sclerosis et atrophicus (13%) Pigmented purpuric dermatitis Pityriasis lichenoides (60%) Interface dermatitis Clonal T-cell populations have been found Surg Path Clinics (10) 2017, 455-476
- 55. Other ‘named’ pseudolymphomas Acralpseudolymphomatous angiokeratoma Angiolymphoid hyperplasia with eosinophilia Cutaneous plasmacytosis Lymphoplasmacytic plaque Pseudolymphomatous Folliculitis
- 56. Acral pseudolymphomatous angiokeratoma Children Benign vascularprocess Prominent lymphocytic infiltrate Unilateral eruption Clustered red to violaceous angiomatous papules (1–5 mm) on acral sites Dense infiltrate of small lymphocytes (polyclonal T cells and B cells), eosinophils, plasma cells, histiocytes, and sometime histiocytic giant cells Within the infiltrate there are thick-walled vessels lined by plump endothelia Am J Surg Pathol 2008 (32), 1468–78.
- 57. Dense infiltrate ofsmall lymphocytes (polyclonal T cells and B cells), eosinophils, plasma cells, and histiocytes, and sometime histiocytic giant cells Thick-walled vessels lined by plump endothelia, surrounded by plasma cells
- 58. Angiolymphoid hyperplasia with eosinophilia Epithelioidhemangioma M=F Angiomatous pink to red- brown papules or nodules Head and neck, especially on the face and ears Dermal proliferates of capillary vessels with prominent endothelia Dense lymphocytic infiltrate with reactive germinal centers and eosinophils Endothelial cells were positive for CD31 and ERG but negative for podoplanin/D2-40. Majority of lymphocytes are of T-cell lineage. Admixed B cells may form lymphoid follicles. Clonal T cells have been detected J Am Acad Dermatol 2016 (74), 506–512
- 59. Prominent endothelia withtypical vacuolization. The vessels are surrounded by a dense lymphocytic infiltrate, consisting eosinophils and plasma cell. Reactive germinal centers Multiple red-brown nodules around the ear Circumscribed proliferates of capillary vessels in the deep dermis and superficial subcutis. Surrounded by a dense lymphocytic infiltrate with reactive germinal centers
- 60. Cutaneous plasmacytosis Rare disease, Reportedin Asian countries Affects adults. Multiple brownish small plaques and nodules occurring all over the body Dermal infiltrates composed predominantly of mature polyclonal plasma cells. Signs of a systemic involvement (lymphadenopathy, hepatospenomegaly, hypergammaglobulinemia, increased levels of interleukin 6 in the serum, and elevated erythrocyte sedimentation rate) J Am Acad Dermatol 2013 (68)978–85.
- 61. Reddish brown papules,patches and plaques in the axilla Epidermis shows acanthosis. There is a dense superficial and mid perivascular infiltrate of plasma cells and lymphocytes No light chain restriction is seen when stained with kappa and lambda, respectively
- 62. Lymphoplasmacytic plaque Rare disease Childrenand adults F> M Pretibial, trunk and arms Longstanding plaque or circumscribed, often linear arranged reddish and brownish papules and plaques Superficial, bandlike, or deep nodular and interstitial infiltrate, An epidermal hyperplasia is common. Lymphocytes and histiocytes with numerous polyclonal plasma cells accounting for up to 25% The interstitial histiocytes may form granulomas around sclerotic collagen bundles (so-called pseudorosettes) Histiocytic giant cells and an increased number of vessels Arch Dermatol 2010 (146), 95–6.
- 63. Longstanding sharply demarcatedreddish plaque with scaling The infiltrate consists of lymphocytes, histiocytes, and plasma cells Epidermal hyperplasia with a bandlike and superficial perivascular infiltrate Interstitial histiocytic granulomas around sclerotic collagen bundles
- 64. Pseudolymphomatous Folliculitis Solitary nodulepreferentially located on the face T-cell predominance. Admixed epithelioid histiocytes and granulomas The lymphocytic infiltrates are located throughout the dermis and may extend into the subcutis The epidermis spared. There is exocytosis of lymphocytes into the hair A hyperplasia of eccrine and apocrine ducts is often observed An admixture of numerous dendritic cells with expression of CD1a and S-100 was identified in all cases. Unusual high number (approximately 50% of the cases) of clonal T cells Am J Surg Pathol 1999 (23),1313–9.
- 65. The lymphocytic infiltratesare located throughout the entire dermis and may extend into the subcutis Exocytosis of lymphocytes (arrow) into the hair follicles
- 66.
- 67. Intravascular pseudolymphoma Intravascular proliferationof blasts with or without expression of CD30 Inflammatory skin diseases or trauma to the skin Obstruction of lymphatic vessels due to inflammation with disrupted immune cell trafficking may result in the accumulation of activated CD30+ lymphocytes Express T-cell markers (CD3 and CD4) and in some cases CD30. No association with Epstein-Barr virus infection. Clonality studies reveal the polyclonal nature of the process Am J Dermatopathol 2013 (35), 143–50.
- 68. The vessels arefilled with activated large lymphocytes The intravascular lymphocytes are positive for CD30
- 69. Pseudo-clonality “Refers to detectionof a clone that on double or triple testing appears at a different position” Br J Dermatol (159)2008
- 70. Pseudolymphomatous drug eruption- pseudoclonal IgH rearrangement
- 71. Pseudolymphomatous folliculotrophic lesion- pseudoclonal TCR rearrangement
- 72. Pseudo-clonality Artefact of PCRas it is very sensitive Picks up small groups of cells Carry out analyses in duplicate and/or analyze multiple or alternative targets Integrate the results with histopathological information Ther Adv Hematol (5) 2014
- 73. Case of SLEpresenting with Mycosis Fungoides
- 74. Summary • Not alllymphoid aggregates are lymphomas • A vast spectrum of pseudolymphoma exists • Key to diagnosis is clinic-pathological correlation • Interpretation of immunohistochemistry should include • Proportion of cells • Distribution of cells • Be aware of the concept of pseudo-clonality
- 75.