Lymphomas of the Head and Neck Tal Marom, MD

Lymphoma Cancer of the lymphatic system Lymphoma is differentiated by the type of cell that multiplies and how the cancer presents itself Two main groups: Hodkgin’s disease and NHL US prevalence (HD) = 3 cases/100,000 (incidence ↓) US prevalence (NHL)=16 cases/100,000 (incidence↑)

Hodgkin vs. Non-Hodgkin Ly. Non-Hodgkin's Lymphomas Hodgkin's  Lymphoma Average age is about 67.  Average age is 27.7 with two age peaks, the major one between 15 and 24 with a lesser peak after age 55. Age Men 2.12% Women 1.79% Men 0.23% Women 0.20% Lifetime prevalence About 85% of all lymphomas About 15% of all lymphomas Occurrence

Hodgkin vs. Non-Hodgkin Ly. Non-Hodgkin's Lymphomas Hodgkin's  Lymphoma LN above the collar bone. In NHL it is also more likely to appear in the mesenteric nodes in the abdomen. The disease occurs in the chest cavity in less than 40% of patients. (An exception, lymphoblastic lymphoma, which is seen most often in young people, is likely to first appear in the chest.) Extra-nodular disease in about 23% of patients. Slow-growing lymphomas are common in the liver and bone marrow. LN above the collar bone. In Hodgkin's it is also more likely to appear in the chest cavity (mediastinum), particularly in younger patients. Only about 15% to 20% of cases are below the diaphragm. Extra-nodular disease in about 4% of cases. Location

Hodgkin vs. Non-Hodgkin Ly. Non-Hodgkin's Lymphomas Hodgkin's  Lymphoma B-Lymphocytes (>90%), T-Lymphocytes or Natural Killer (NK) Cells B-Lymphocytes characterized by the Reed-Sternberg Cell Affected Lymph Cells Less likely than HL to have systemic ("B") symptoms (27%) at the time of diagnosis. More likely (40%) to have systemic ("B") symptoms at the time of diagnosis. Symptoms More likely than HD to be diagnosed in stage IV (36%) but this will vary by NHL subtype.  The Non-Hodgkin's lymphomas are less predictable in their course than Hodgkin's and they are more apt to spread Less likely to be diagnosed in stage IV (10%). Hodgkin's disease usually progresses slowly (or aggressively) in an orderly way from one lymph node region to the next. If it spreads below the diaphragm, it usually reaches the spleen first; the disease then may spread to the liver and bone marrow. If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs. Progression

Reed Sternberg Cell

H&N Lymphoma Lymphoma is the second most common primary malignancy occurring in the head and neck, and incidence of aggressive non-Hodgkin lymphoma is rising in young and middle-aged patients. 25% of all extra-nodal lymphomas occur in the head and neck, and 8% of supraclavicular fine-needle aspirates are diagnosed as lymphoma. REAL classification (Revised European American Lymphoid neoplasm) : indolent, aggressive and Hodgkin disease

Clinical presentation Neck- lymphadenopathy, ulcerated mass Oropharynx- enlarged tonsil, tongue base thickening Nasopharynx – mass, SOM Nose & paranasal sinuses- ulcerated destructive lesion –susp. NK/T cell Lymphoma (“midline lethal granuloma”), associated with EBV Thyroid - neck swelling, hoarseness, dysphagia, or neck pressure/tenderness Salivary glands- masses Base skull – cranial neuropathy, facial pain, hearing loss, vertigo, proptosis, or visual symptoms

Physical examination History – cough, fever, GI, abdominal masses, pruritus Full PE, look for peripheral adenopathy

Differential diagnosis infectious etiologies Bacteria Viruses (eg, infectious mononucleosis, cytomegalovirus, HIV) Parasites (eg, toxoplasmosis) Nasal granulomatous disease Wegener granulomatosis Lymphomatoid granulomatosis Infections (eg, leishmaniasis, syphilis, TB) Mediastinal presentation Infections (eg, histoplasmosis, tuberculosis) Sarcoidosis Other neoplasms Benign lymphoid hyperplasias B-cell predominant - Cutaneous lymphoid hyperplasia (CLH), angiolymphoid hyperplasia with eosinophilia, Kimura disease, and Castleman disease T-cell predominant - T-cell CLH, lymphomatoid contact dermatitis, and lymphomatoid drug eruption Other neoplasms Squamous cell carcinoma Nasopharyngeal carcinoma Thyroid carcinoma

Lab studies CBC Chemistry, liver, LDH ESR Urine Serum β2 microglobulin (worse prognosis) CXR Total body CT Galium scanning Genetic studies

Procedures Fiberoscopy- NPH, larynx FNA-C from neck mass Excisional/Incisional Bx Diagnostic TE (Bone marrow, LP, liver, explorative laparotomy…)

Ann Arbor Lymphoma staging Stage I - Involvement of a single LN region/ lymphoid structure Stage II - Involvement of 2 or more LN regions on the same side of the diaphragm or localized contiguous involvement of only one extra-lymphatic site and LN region Stage III - Involvement of LN regions or lymphoid structures on both sides of the diaphragm Stage IV - Disseminated involvement of one or more extra- lymphatic organs with or without LN involvement and/or involvement of the bone marrow or liver

Chemotherapy – major modality Radiotherapy Surgery ??? Relapse !!! Treatment Chemotherapy – major modality Radiotherapy Surgery ??? Relapse !!!

Chemotherapy Hodgkin disease – - MOPP (mechlorethamine [nitrogen mustard], vincristine, procarbazine, and prednisolone) [2% post-Rx ALL, infertility] - ABVD (doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine) - For advanced disease : BEACOPP (cyclophosphamide, doxorubicin, etoposide, procarbazine, prednisolone, vincristine, and bleomycin with granulocyte colony-stimulating factor)

Chemotherapy Non-Hodgkin Lymphoma: CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) Purine analogues

Other procedures Stem cell transplantation IL-2 Recomninat INF-α Bone marrow transplantation?

Radiotherapy Mantle field includes the submandibular, cervical, supraclavicular, infraclavicular, axillary, mediastinal, and hilar lymph nodes It can be extended to cover the Waldeyer ring and the skull base with lateral portals for lymphomas involving the skull base Combined= Chemo + Radio

Surgical treatment Excision of necrotic tissue may be necessary in nasal NK/T-cell lymphoma MALT lymphomas are often treated surgically with or without local radiotherapy Lymphomas of the CNS and skull base are treated with surgical decompression when necessary