oral lymphoma

oral lymphoma

1. ORAL LYMPHOMA UPAMA SISHAN

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4. Hematopoietic stem cell Neutrophils Eosinophils Basophils Monocytes Platelets Red cells Myeloid progenitor Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes na ï ve germinal center

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7. 10 Centrocytes ( small cleaved cells) Small cells Cytoplasm - scant Irregular or cleaved nuclear contours Condensed chromatin These cells are majority in follicular lymphoma Centroblasts Large cells Cytoplasm – moderate Nuclei – round Regular nuclear contour With open nuclear chromatin Nucleoli – multiple and several (bound to the membrane) Tumors showing these cells Follicular lymphoma

8. ALL MM CLL Lymphomas Hematopoietic stem cell Neutrophils Eosinophils Basophils Monocytes Platelets Red cells Myeloid progenitor Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes na ï ve germinal center

9. 12 Definition Malignant lymphoma is a neoplastic proliferative process of the lymphopoietic portion of the reticuloendothelial system that involves cells of either the lymphocytic or histiocytic series in varying degrees of differentiation and occurs in an essentially homogenous population of a single cell type. ( Lukes )

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11. EVOLUTION OF LYMPHOMA CLASSIFICATION Rappaport ( considered cytologicaland architectural features)(1966) Lukes and Collins ( immunophenotype )(1973) Kiel Classification(Europe )(1973) WorkingFormulation (USA) R EAL Classification(1992) WHO classification(2001) Update of WHO classification(2008

12. CLASSIFICATION Rappaport Classification (1966) First popularly used system Divided growth patterns into nodular and diffuse; Cells types into well differentiated, poorly differentiated (cleaved follicular center cells), histiocytic (large cells) undifferentiated (round; between lymphocytes and histiocytic), and Burkitt’s . Lukes -Collins Classification (1973) Based on proposed cell of origin; follicular center cells, cleaved or uncleaved ; immunoblasts ; B or T Cells Kiel Classification (1973) Based on low and high grade, Centroblastic , Lymphoblastic, Immunoblastic Low grade: Lymphocytic, Lymphoplasmacytoid , Centrocytic , Centroblastic

13. WORKING FORMULATION FOR CLINICAL USE (1982) Establish a common language of communication between pathologists and clinicians rather than to represent specific disease entities. An individual patient can progress from one histologic type to another Low Grade : Small lymphocytic, follicular small cleaved,follicular mixed(small cleaved and large cell) Intermediate Grade : follicular large cell, diffuse large cell, diffuse small cleaved cell, diffuse mixed (small and large cell) High Grade : Immunoblastic , lymphoblastic, small non-cleaved. Misc : Composite, Mycosis fungoides , Histiocytic, Extramedullary plasmacytoma , Others

14. REAL/ WHO 2001/ WHO 2008 CLASSIFICATION OF B – CELL LYMPHOMAS

15. REAL/ WHO 2001/ WHO 2008 CLASSIFICATION OF THE T/NK CELL LYMPHOMAS

16. 2008 WHO Classification of Hodgkin Lymphoma 19 A B 5 UNCLASSIFIED

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18. HODGKIN LYMPHOMA 21

19. 22 Definition (WHO) HL is a type of malignant lymphoma in which Reed-Sternberg cells are present in a “characteristic background” of reactive inflammatory cells of various types, accompanied by fibrosis of a variable degree.   Histogenesis Tumors of B cell origin - germinal center or post germinal center B cells HODGKIN LYMPHOMA It was named after Thomas Hodgkin who first described it in 1832. Dorothy Reed & Carl Sternberg first described the malignant cells of HL called Reed Sternberg cells. Cervical lymphadenopathy is the most common head and neck presentation for Hodgkin's lymphoma (HL). extranodal HL typically associated with generalized disease & a consequence of local spread from adjacent lymph nodes.

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21. A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV ? cytokines 24

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23. 26 FORMATION OF REED STERNBERG CELLS EBV Infects B cells Which has undergone VDJ recombination somatic hypermutation Will express LMP1( protein encoded by EBV genome) upregulates NF kb Which rescues crippled germinal centre B cells that cannot express Igs from apoptosis Promote lymphocyte survival & proliferations Produce reed sternberg cells

24. REED-STERNBERG CELL 27 Classic Reed-Sternberg cell: + CD15, CD30, CD25 – CD45, pan-B, S-100, keratin, EMA

25. RS Cell Variants

26. 29 MUMMIFIED CELL VARIANT

27. 30 SYNCYTIAL VARIANT

28. 31 NODULAR LYMPHOCYTE PREDOMINANT

29. 32 LYMPHOCYTE RICH

30. 33 NODULAR SCLEROSIS

31. Nodular sclerosis type. A low-power view shows well-defined bands of pink, acellular collagen that subdivide the tumor into nodules 34

32. 35 MIXED CELLULARITY

33. LYMPHOCYTE DEPLETED 36

34. 37 HODGKINS LYMPHOMA IN ORAL CAVITY Primary / relaspsed HL in oral soft tissue & jaws are rare oral mucosa – only 12 cases jaw – extremely rare The primary site - Waldeyer’s ring Nasopharynx Tonsil base of tongue posterior pharyngeal wall  DISSEMINATED HL more common – only 5 cases (tongue, palate, tonsil)

35. 38 A 71 year old male presented with a swelling in the left mandibular buccal vestibule and buccal mucosa, lateral to his left mandible. NODULAR SCLEROSIS

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37. NON-HODGKIN’S LYMPHOMAS ( nhls ) represent a heterogeneous group of malignancies that arise from the lymphoid system which can involve - both lymph nodes & lymphoid organs extranodal organs & tissues In oral cavity: NHLs of the oral cavity are rare A ccount for only 2-3% of all the lymphomas reported. Oral cavity - large B cell lymphoma – 60% Of cases

38. PATHOGENESIS :

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41. 44 Anatomic location of thirty-one cases of NHL in the oral region arising in soft tissues

42. 45 Oral manifestations Disease of oral cavity is extranodal . The disease can be due to Manifestation of disseminated disease Primary disease of the oral tissues and has not spread to other sites. (Sole expression of the disease or the initial manifestation of generalized disease). Oral sites Oral soft tissues Centrally within jaws . Presentation – oral lesions grow rapidly and then ulcerate. Some cases they can become large, fungating , necrotic, foul smelling masses. Soft tissue mass N on tender diffuse swellings. Most common buccal vestibule, posterior hard palate or gingiva. swellings have a boggy consistency. Lesion may be erythematous or purplish. May or may not be ulcerated .

43. 46 Lymphomas of bone in oral cavity vague pain or discomfort which might be mistaken form toothache . Tooth mobility and pain may develop. Parasthesia in the mandible (numb chin syndrome) Ulcerated – then bony expansion eventually perforating the cortex producing a soft tissue swelling. Systemic symptoms like fever, night sweats, weight loss and fatigue, pruritis noted .

44. 47 Of a total of 1,467 cases of extranodal NHL studied by Freeman and co-workers 417 ( 28percent ) - head and neck region. T onsils , 32 % Salivary glands 16.5 % O ral cavity 9.5 % Nasopharynx - 8.8 % Thyroid - 8.6 % Nose - 7.9 %

45. 48 characterized by diffuse proliferation of large neoplastic B-lymphoid cells with nuclear size equal to or exceeding normal macrophage nuclei or more than twice the size of a normal lymphocyte (>20 μm ). 7th decade of life clinically a rapidly enlarging often symptomatic mass is typically seen Extraoral sites : mediastinum , GIT, bone marrow, CNS, breast & testes. Oral site: Waldeyer's ring, maxillary alveolus, maxillary vestibule & posterior palate . DIFFUSE LARGE B-CELL LYMPHOMA

46. 49 C entroblasts ( large atypical pleomorphic lymphocytic nucleus with multiple nucleoli) Swelling in the anterior hard palate with surface ulceration

47. 50 SUBCLASSIFICATION OF DLBCL affecting oral cavity

48. 51 CLINICAL, HISTOLOGICAL AND IMMUNOLOGICAL DD OF DLBCL

49. 52 CLINICAL, HISTOLOGICAL AND IMMUNOLOGICAL DD OF DLBCL

50. 53 Oral PBL is rare recently described B-cell derived lymphoma most commonly seen in patients with HIV infection. characterised by a diagnostic triad of predilection for Gingivo-buccal complex mucosa, C lassical plasmablastic morphology with the lack of neoplastic plasma cells A limited immunohistochemical panel CD20 negativity LCA (+/), CD138/VS38c diffuse positivity , light chain restriction & high Mib-1(Ki 67) index. Prognosis is usually poor regardless of the site of origin. PLASMABLASTIC LYMPHOMA

51. 54 Plasmablastic lymphoma PBL has found a place in the World Health Organization (WHO) 2000 classification as a distinct type of AIDS-related lymphoma and is accepted to be a variant of DLBCL.

52. 55 BURKITT LYMPHOMA highly aggressive NHL that has the highest cell proliferation rate among human neoplasms. occurs predominantly in the first decades of life mostly in males with significant affinity for gnathic bones – 50 – 70% cases maxilla: mandible – 2:1 Posterior segments of the jaw Sometimes – 4 quadrant involvement Jaw involvement seems to be age related: 90% - 3 yrs old pt 25% - pts older than 15 yrs

53. 56 There are three clinical variants of BL : E ndemic BL - children in Africa and Papua New Guinea as jaw or orbital masses S poradic BL- no specific age or geographic predilection and occurs with abdominal or nodal involvement HIV associated BL

54. 57 A retrospective review of patients with Burkitt's lymphoma in the facial (1978 - 1997) . SITES: mandible, maxilla , palate TUMOUR- facial swelling / exophytic mass / as an ulcer..

55. 58 H/P: sheets of round cells with vesicular nuclei & indistinct cytoplasm interspersed with lymphocytes with condensed nuclei. Few macrophages were seen between the tumour cells  .

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57. 60 MANTLE CELL LYMPHOMA MCL includes small-medium sized lymphoid cells and accounts for 6–10% of all B-cell lymphomas . Common extra-nodal sites - RARE Waldeyer's ring, gastrointestinal tract, bone marrow and peripheral blood. INTRORAL: 9 cases Common site: palate….floor of mouth…Base of tongue Palatal MCL is mostly seen in elderly people and may be masked with the presence of prosthesis

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59. 62 Nuclei of small cells have distinct hyperchromatism . Mild nuclear pleomorphism is also evident Diffuse small cell lymphocytic infiltration is the predominant component on histology .

60. 63 Tumoral cells stained diffusely positive with CD20 Tumoral cells showed nuclear positivity with cyclin D1 staining

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62. 65 FOLLICULAR LYMPHOMA: Follicular lymphomas accounts for one third of NHL . This is a low to intermediate grade lymphoma show a follicular architecture represents the neoplastic counterpart of germinal center B lymphocytes. Few case reports – in salivary glands Among lymphomas originating from salivary glands, the ratio of follicular lymphoma is very low.

63. 66 A case follicular lymphoma which presented as a salivary gland tumour – submandibular gland Destruction of salivary gland architecture. No acinar cell/ducts were seen . The entire mass was infiltrated by proliferation of lymphocytes which were arranged in sheets .. neoplastic lymphocytes in a follicular pattern .

64. 67 Photomicrograph showing neoplastic cells expressing strong positivity for Bcl-2. neoplastic cells expressing strong positivity for CD20

65. EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA Lymphoma of MALT. I ndolent lymphoma in mucosal sites and in extranodal tissues including the gastrointestinal tract, salivary glands , lung , thyroid gland, and skin. Any age-group or gender can be affected A ssociated with Sjogren's syndrome female predominance. Populated by lymphocytes such as T cells and B cells, as well as plasma cells and macrophages

66. 69 Sheets of monocytoid B cells & includes lymphoepithelial formations IMMUNOPHENOTYPE CD 19 + CD 20 + CD 10 – ( FOLLICULAR L) CD 5 -- (MANTLE CELL L)

67. 70 MYCOSIS FUNGOIDES – Cutaneous T-cell lymphoma /SEZARY SYNDROME is a distinctive variant of NHL Characterized by a malignant proliferation of helper (CD4+) T-lymphocytes & less commonly suppressor (CDS +) T-lymphocytes. with a predilection to involve the skin . The mouth is an rare site only 31 cases of oral CTCL have been reported in E nglish literature Oral lesions almost always develop after cutaneous lesions

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69. 72   Clinical presentation ulcerated tumors , indurated plaques, papules, leukoplakia -like lesions, nodules, and multiple erosions Dysphagia commonly associated Oral lesions appear to be a late manifestation of mycosis fungoides that arise on skin

70. 73 consist of a dense infiltrate of atypical pleomorphic lymphocytes. characteristic Pautrier's microabscesses can be found . These features are similar to those seen in cutaneous lesions

71. 74 EXTRANODAL NASAL-TYPE NATURAL KILLER (NK)/T-CELL LYMPHOMA Represents a rare entity Typically originating in the nasal cavity palate or midfacial region. Signs and symptoms non-specific rhinitis and/or sinusitis nasal obstruction epistaxis , facial swelling development of deep necrotic ulceration in the midline of the palate, causing an oronasal defect. Differential diagnosis: fungal infections, Wegener’s granulomatosis , tertiary syphilis, other non-Hodgkin’s lymphomas & malignant epithelial midline tumors .

72. 75 NASAL EXTRANODAL NK/T-CELL LYMPHOMA

73. 76 LYMPHOMAS OFSALIVARY GLANDS LYMPHOMAS – LYMPH NODES LYMPHOID TISSUES EMBEDDED IN SG 1.7% - BRITISH SERIES OF 40 CASES OF SG TUMOURS 2.45% – AMERICAN SERIES OF 366 CASES LOW GRADE LYMPHOMA - Predominant in all studies HIV/AIDS Associated – high grade large cell lymphoma

74. 77 P arotid gland 80% of cases S ubmandibular gland (16 %) S ublingual gland and minor salivary glands (2 %).

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76. 79 PATHOGENESIS: Lymphoid tissues closely asso with SG Especially parotid gland- 5 – 10 lymph node embedded Several lymph node – submaxillary gland SG acini & ducts present in medulla of upper cervical lymph nodes These nodes – target for viral/bacterial infections anti- immune diseases Lymphomas – site for long standing benign lesions Sjogrens lymphadenopathies HIV lymphadenitis COMMON – 1. Marginal zone Bcell L 2. DLBCL

77. Ann Arbor Staging System Stage I: S ingle lymph node region (I) or single extralymphatic organ or site (I E ) Stage II: > 2 lymph node regions on same side of diaphragm (II) or with limited, contiguous extra lymphatic tissue involvement (II E ) Stage III: both sides of diaphragm involved, may include spleen (III S ) or local tissue involvement (III E ) Stage IV : multiple/disseminated foci involved with > 1 extralymphatic organs (i.e. bone marrow) or (B) designates absence/presence of “B” symptoms * (E) Localized, solitary involvement of extralymphatic tissue, excluding liver and bone marrow 80

78. Stage I Stage II Stage III Stage IV Staging of lymphoma A : absence of B symptoms B : fever, night sweats, weight loss 81

79. DIAGNOSIS Blood test Lactate Dehydrogenase (LDH) Biopsy Bone Marrow Biopsy CT, and PET scans

80. Immunohistochemistry Flow Cytometry Fluorescence in Situ Hybridization (FISH ): to detect changes in specific chromosomes. Polymerase Chain Reaction (PCR ): to detect specific DNA sequences that occur in some cancers DNA Microarray

81. 84 Oral lymphoma often is a component of a disseminated disease process that may involve regional nodes as well. Other times, it may represent a primary extranodal disease confined to oral cavity or jaws, which is very rare

82. 85 REFERENCES: IOACHIMS – Lymph node pathology 4 th edition NEVILLE – Oral and maxillofacial pathology SHAFERS - Oral and maillofacial pathology ROBBINS – B asic pathology 8 th edition Eisenbud L,Oral presentations in non-Hodgkin's lymphoma: a review of thirty-one cases. Part II. Fourteen cases arising in bone. Oral Surg Oral Med Oral Pathol . 1984;57:272–80 . Kolokotronis , et al. Localized B-cell non-Hodgkin's lymphoma of oral cavity and maxillofacial region: A clinical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod . 2005;99:303–10.

83. 86 Vega F, Lin P, Medeiros LJ: Extranodal lymphomas of the head and neck. Ann Diagn Pathol 9:340, 2005 Wertheim L, Smith GS. Mycosis fungoides . Arch Dermatol Syphilol 1948; 57: 625 ± 635 . Tolman MM. Mycosis fungoides in a 56-year-old woman. Arch Dermatol Shypilol 1949; 60: 929 ± 930. Cho G, Suh IS, Tak KS, Park YK, Ko EY, Sung HM, et al . Primary Parotid Non-Hodgkin’s lymphoma: Case report. J Korean Cleft Palate- Craniofac Assoc 2010;11:99-102. Armstrong R, Bradrick J, Liu Y. Spontaneous regression of an HIV-associated lymphoblastic lymphoma in the oral cavity: a case report. J Oral Maxillofac Surg 2007: 65: 1361–1364 Borrero JJ, Pujol E, Perez S, Merino D , Montano A, Rodriguez FJ. Plasmablastic lymphoma of the oral cavity and jaws . AIDS 2002: 16: 1979–1980.