--------------------------------------------------------------------------- TITLE: Granulomatous Diseases of the Head and Neck SOURCE: Dept. of Otolaryngology, UTMB, Grand Rounds DATE: 15 May 1991 RESIDENT PHYSICIAN: Mark C. Littlejohn, M.D. FACULTY: Byron J. Bailey, M.D. DATABASE ADMINISTRATOR: Melinda McCracken, M.S. --------------------------------------------------------------------------- "This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purpose of stimulating group discussion in a conference setting. No warranties, either express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion." I. Granuloma A. Formation: Granuloma is a pathologic term used to describe the end result of a defensive immunopathologic process. The lesion begins with the appearance of a circulating monocyte, which then acquires additional cytoplasm and organelles in the process of removing inflammatory debris. The phagocytic mechanism eventually fails and the cell becomes "epithelioid", being inert and immobile. The relatively functionless multinucleated Langhans giant cell then develops from this cell, with lymphocytes and eosinophils congregating. Finally, a fibroblastic proliferation occurs about the involved cells, forming a granuloma. B. Introduction: When presented with a nonhealing, ulcerative or erosive lesion in the head and neck, or with a mass in the neck, biopsy or fine needle aspiration is frequently performed to rule out a neoplastic process. If the pathology report states only the presence of granulation tissue consistent with acute and chronic inflammation, then the surgeon is faced with narrowing down a rather large differential diagnosis. It is important to determine whether the lesion is a localized disease process or a regional presentation of a systemic disease. The investigation begins with a thorough history, including inquiry about night sweats, weight loss, loss of appetite, malaise, arthralgias and other factors suggestive of a systemic disease, recent travel to Third World countries, and presence of immunocompromise. Physical examination should include a search for cervical, axillary, or inguinal nodes, and abdominal exam to rule out hepatosplenomegaly. If the first biopsy is inadequate, a subsequent biopsy specimen from either the superficial margins of the lesion or from its depths must be obtained. Tissue is also sent for culture and special stains. Consultation with the pathologist/microbiologist preoperatively is essential to ensure proper specimen collection and transportation. Recommended- immediate aerobic, anaerobic, fungal cultures, followed by air-dried imprint slides and imprint slides in 95% ethanol for atypical cell examination, and finally frozen-section to immediately assess the condition of the tissue prior to termination of the procedure. Laboratory evaluation should include CBC with manual differential, ESR, RPR, SPE, UA, chem 7, chem 12, LE prep, ANA, circulating immune complexes (C1q), PPD, and antigen skin tests. One must also consider obtaining a CXR and CT of the head and neck. Remember, an accurate diagnosis is of paramount importance since treatment by surgery, radiation, chemotherapy, antimicrobials, or immunosuppressants are all considerations in the treatment of granulomatous disorders of the head and neck. II. Disease Classification A. Neoplastic Disorders 1. Squamous Cell Carcinoma- Frequently present, as do other entities to follow, as an ulcerative lesion. Rarely missed on microscopic exam unless a necrotic center is biopsied. 2. Undifferentiated Carcinoma and Nonkeratinizing Carcinoma of the Nasopharynx 3. Adenocarcinoma 4. Histiocytosis X- Unifying feature: histopathology- sheets of polygonal histiocytes with a variable number of eosinophils, plasma cells, and lymphocytes. Possible presentations: 1. Otologic- swelling over mastoid, EAC granulation tissue, otorrhea, deafness, facial paralysis, otitis media (most frequent otologic finding); 2. Oral lesions- especially gingival swelling, pain, loose or premature loss of teeth (R/O histiocytosis X in child with loose teeth of unexplained etiology); 3. Skin (disseminated forms)- scaly, yellow-brown, greasy, papular rash with purpura and petechial hemorrhages; 4. Bone- most frequent manifestation, especially flat bones (calvarium most frequent), with sharply marginated, round to oval lucencies with scalloped edges by x-ray; 5. Neuroendocrine (disseminated forms)- diabetes insipidus, delayed growth, hypogonadism, truncal ataxia, intention tremors, seizures, cranial neuropathies; 6. Hematologic (disseminated forms)- anemia, leukocytosis, mild thrombocytopenia, elevated ESR; 7. Pulmonary- bilateral diffuse pulmonary infiltrates with a reticular or reticulonodular pattern, fibrosis; 8. GI (disseminated forms)- hepatosplenomegaly, malabsorption; 9. Lymph system (disseminated forms)- predilection for anterior cervical lymphadenopathy. a. Eosinophilic Granuloma- Occurs in children and young adults. Characterized by osteolytic lesions in one (monostotic) or several (polyostotic) bones, with a predilection for the frontal and temporal bones. Treatment: Surgical excision. XRT for recurrences or inaccessible lesions. Excellent prognosis. b. Hand-Schuller-Christian Disease- Chronic disseminated form of histiocytosis X. May be the polyostotic form of eosinophilic granuloma. Occurs in children (not infants) and young adults, but is also described in the elderly. Triad, occuring in 10%- skull lesions, exopthalmos, diabetes insipidus. Treatment: XRT. Mortality 30%. c. Letterer-Siwe Syndrome- Acute disseminated form. Infants less than three years old affected. Extraskeletal involvement predominates. 5. T-Cell Disorders a, b. Polymorphic Reticulosis (PMR, also called malignant midline reticulosis) and Lymphomatoid Granulomatosis- Show identical histology, namely, infiltrates of atypical hematopoietic cells centered around vessels, but without granuloma formation or true vasculitis. As such, these two disease processes are felt to be one and the same. Probable T cell origin (controversial). May be a precursor to true lymphoma. 1) Clinical Features- Lesion may involve the midface, lungs, kidneys, CNS, GI tract, and skin. (Usually begins in the nose or paranasal sinuses.) Nasal obstruction and bloody nasal discharge are the most frequent initial symptoms. May also have constitutional symptoms. Prodromal Stage- nasal stuffiness with clear rhinorrhea, no gross lesions. Active Stage- purulent or sanguinopurulent rhinorrhea, ulceration/perforation of the septum, ulceration of the hard palate, epistaxis, massive destruction of facial tissue, fever. Terminal Stage- fever, epistaxis, sloughed tissues, death. Skin involvement always occurs: maculopapular rash=> ulceration. Pulmonary: cough, fever, chest pain, hemoptysis. 2) Treatment- Localized: XRT, may require orbital exenteration. After XRT, debridement when necessary, with treatment of concurrent infections (usually Staph. aureus). Systemic: none, fatal regardless of therapy. 6. Sarcomas- Granulocytic sarcomas (chloromas) are composed of immature myeloid precursor cells in an extramedullary site. 7. Lobular Capillary Hemangioma (LCH)- Also called pyogenic granuloma, although this term is used to describe granulation tissue not caused by hemangioma. Histologically, LCH consists of circumscribed aggregates of capillaries arranged in several lobules. Clinically, these are most frequently seen on the lip (38%), nasal cavity (29%), tongue (18%), and oral mucosa (15%). 60% of nasal lesions arise on the septum. These lesions characteristically bleed intermittently, but are painless. Sex distribution- <18 y/o: 82% males, 18-39 y/o: 86% females. May be hormonally related- LCH in pregnant women shows marked regression with delivery; also, progesterone increases the size of the vessels in the oral cavity lesions in animal models. Treatment- excision. 8. Granulomatous Reaction with Malignant Disease- Mycobacterial and fungal disease must be sought when granulomatous reactions are associated with malignancy. a. Solid Tumors- Nasopharyngeal carcinomas may produce granulomatous reactions with caseous necrosis in metastatic lymph nodes. Testicular seminoma commonly elicits epithelioid granulomatous reactionsin lymph node metastasis, which may present as supraclavicular nodes. b. Hodgkin's Lymphoma- Frequently, epithelioid granulomas are found in association with Hodgkin's disease. Granulomatous involvement of a lymph node usually does not indicate active Hodgkin's disease in that node. Sachs et al feel the presence of granulomas in other nodes represents a favorable prognostic sign. Granulomatous reactions related to malignant disease is most commonly associated with Hodgkin's. c. Non-Hodgkin's Lymphoma- Granuloma may obscure the presence of an underlying lymphoma. d. Squamous Cell Carcinoma- Lymph nodes may or may not harbor metastatic SCCA in conjunction with epithelioid granulomas. A high index of suspicion is necessary with the finding of granuloma in a lymph node in a patient at high risk for development or recurrence or SCCA. B. Necrotizing Sialometaplasia- Composed of metaplastic epithelial cells lining small salivary gland ducts with PRESERVATION OF LOBULAR ARCHITECTURE (as opposed to SCCA or mucoepidermoid CA). Found anywhere salivary tissue is present, but most common in the oral cavity. The most frequent site of involvement is the junction of the hard and soft palate. If extraoral, it is usually secondary to surgical manipulation and compromise of local blood supply. Present clinically as an ulcer, being deep-seated and sharply demarcated. However, may present as a nonulcerated swelling. This entity is more common in smokers. Spontaneous resolution over weeks to months is the rule. C. Inflammatory Diseases of Unknown Etiology 1. Sarcoidosis- A multisystem granulomatosis of unknown etiology whose clinical course can vary from spontaneous resolution to chronic pregression and death. a. Incidence- Onset most commonly occurs in the third to fifth decades, with a predilection for blacks and females. b. Pathology- Discrete noncaseating epithelioid granulomas, consisting of epithelioid mononuclear histiocytes and multinucleated giant cells. Microscopic exam alone is not diagnostic. c. Clinical Spectrum 1) Many (40%) asymptomatic, being discovered incidentally by CXR. (most common presentation.) 2) Pulmonary- 88% with lung involvement. Frequently have dyspnea at rest or exertion, and nonproductive cough. CXR staging: 0- normal CXR 1- hilar adenopathy (51%) 2- hilar adenopathy and pulmonary infiltrate (31%) 3- infiltrates without adenopathy (6%) spontaneous remission: 1- 60%, 2- 40%, 3- 12%. 3)Lymph Nodes- 75% with adenopathy (most common H and N manifestation.) 4) Eye- 15-25% with ocular lesions, including choreoretinitis, uveitis, keratoconjunctivitis, glaucoma, and cataracts. Usually bilateral. 5) Skin- 18%. Erythema nodosum, maculopapular rashes, plaques, scars, keloids, lupus pernio. (lupus pernio is a violaceous lesion with a predilection for ears, facial soft tissue, nasal septum and palate. 6) Liver- 18%. May be asymptomatic or as severe as portal HTN. 7) Renal- 10-12%. Nongranulomatous nephritis and hypercalcemic nephropathy. 8) Spleen- 10% with splenomegaly. 9) Parotid- 6%. Heerfordt's Syndrome: facial paralysis + uveitis + bilateral parotid swelling. 10) CNS- 5%. Central and peripheral neuropathies, intracranial masses, and granulomatous leptomeninges. 11) Cardiac- 5%. Affects all layers. May lead to conduction block, other arrhythmias, necrosis, aneurysm, pericardial effusion, and mitral calcification. 12) Bone- 3-5%. Obtain x-rays of hands and feet only if skin lesions present. 13) Head and Neck- 10-15%. Study by Dash and Kimmelman of 42 consecutive patients presenting with head and neck manifestations of sarcoidosis (34 of which previously undiagnosed): cervical adenopathy- 20 enlarged lacrimal glands- 8 eyelid lesions- 9 intranasal mass or nodules- 8 nasopharyngeal lesions- 4 uveitis- 6 orbital mass or swelling- 3 bilateral parotid enlargement- 3 enlarged submandibular glands- 2 skin lesions- 4 nasal septal perforation- 2 tonsillar lesions- 1 laryngeal mass- 1 Salivary involvement in all patients with sarcoidosis is 20-30%. Laryngeal involvement in 5%. Of laryngeal involvement, the supraglottis is most commonly affected, with resultant airway obstruction as the most common laryngeal symptom. (Some studies find hoarseness to be the most common.) TVC lesions rare. Recurrent laryngeal nerve involvement or extrinsic compression may produce TVC paralysis. Laryngeal lesions are characteristically erythematous, edematous, nonulcerated mucosa with nodularity. Esophageal involvement may produce stricture with resultant dysphagia. d. Laboratory Workup- CXR, PPD, skin tests to R/O anergy (86%), CBC, SPE (hypergammaglobulinemia in 20-25%), LFT's (10%- alkaline phosphatase, SGOT, and/or SGPT), chem 7, serum calcium (hypercalcemia in 10-17%), ESR (elevated), EKG, angiotensin converting enzyme. ACE is elevated in 80-90%, and may be used to follow activity of the disease. Minor salivary gland biopsies are positive in 40-50% in those with hilar adenopathy. Parotid biopsy is positive in 93% (incision made in crease of ear lobule). e. Treatment 1) Asymptomatic- no treatment, follow with CXR, physical examination. 2) If any of the following present, treat: progressive pulmonary involvement, ocular involvement, hypercalcemia, hypercalciuria, CNS involvement, myocardial involvement, fever, malaise, weight loss, cutaneous lesions. Treatment is prednisone 60-80 mg qod x 1-2 months, then 20-60 mg qod for 6-8 months, and then taper. Nasal lesions may be successfully treated with submucosal depot injections of corticosteroids or use of nasal steroids. Tonsillar or laryngeal involvement responds well to intralesional corticosteroid injections (kenalog-10 or kenalog-40). f. Prognosis- stage 1: 90% resolve spontaneously stage 2: 33% " " stage 3: 10% " " Of those requiring treatment, 60-70% improve or remain stable. Death usually from pulmonary causes. 2. Idiopathic Midline Destructive Disease- Cause is unknown. Uniformly fatal without treatment. Clinically may present with pansinusitis and erosive ulceration of the nasal floor, septum, paranasal sinuses, hard palate, and facial soft tissues. Extension may occur to the nasopharynx, orbit, larynx, and trachea. High dose XRT to the lesion is the treatment of choice. Consider a trial of chemotherapy initially if the possibility of Wegener's granulomatosis exists. (Differentiated by a lack of a true vasculitis and the absence of granulomas in IMDD.) With XRT, majority go into remission. 3. Autoimmune and/or Vasculitic a. Wegener's Granulomatosis- A systemic disorder characterized by 1. necrotizing granulomas with vasculitis in one or more major organ systems and 2. in the majority, focal necrotizing glomerulonephritis. 1) Etiology- Unknown. Felt to be an autoimmune process, possibly a variant of periarteritis nodosa. 2) Histology- Both granulomas and necrotizing vasculitis must be present for the diagnosis. Arteritis involving small arteries must be demonstrated. 3) Clinical Spectrum- Involvement of any combination of organ systems, with the exception of isolated renal involvement. Most common in the 4th-5th decades of life. Male predominance 2:1. The upper respiratory tract, lungs, and kidneys are the main areas of involvement. Head and neck presentations include: 1. nasal (60-80%)- chronic sinusitis, nasal crusting, bloody rhinorrhea, postnasal drip, septal perforation, 2. serous otitis media (20-25%) with or without accompanying sensorineural deafness secondary to cochlear vasculitis, 3. eyes (40%)- granulomatous keratitis, uveitis, and retinal artery involvement, and 4. tracheal involvement with stridor from subglottic circumferential narrowing. Pulmonary involvement is nearly universal, with cough and hemoptysis heralding large, multiple cavitating lesions. Systemic complaints of malaise, night sweats, migratory arthralgia, and profound weakness also occur. The kidneys, involved in 40-50%, reveal a nonspecific focal glomerulonephritis with elevated serum creatinine, hematuria with blood casts, and proteinuria. Renal disease progresses despite chemotherapy. 4) Diagnosis- Combination of clinical picture, biopsies and exclusion of infectious and other granulomatous diseases. 5) Treatment- Standard therapy: prednisone 60-80 mg/day until ESR and creatinine levels improve, at which time cyclophosphamide is begun at 2 mg/kg/day with dosage adjustment to keep WBCs at 3000-3500/cubic mm with 1000-1500 PMNs/cubic mm. Prednisone dosage is changed (2-3 weeks later as cyclophosphamide begins to take effect) to qod therapy for 1-2 months, with tapering over 6-12 months. Cyclophosphamide is continued for at least a year after the patient is in complete remission, after which time it may be tapered, unless symptoms recur. Prognosis with this regimen is 95% long-term remission (15+ years). Renal failure may require dialysis or transplantation. Newer treatment regimens incorporate trimethoprim/sulfamethoxazole (T/S) in conjunction with standard therapy or alone. The indication as a single agent, as listed by DeRemee, are 1. patients with an indolent course, with disease limited to the nose and/or lungs, in the absence of renal disease and/or rapidly progressing vasculitis. Other recommend the addition of T/S to standard therapy for cytoxic-agent resistant Wegener's. Suggested dosage is T/S double-strength tablets one po bid-tid for 6-8 weeks. Mechanism of action of T/S on Wegener's granulomatosis is unknown. b. Goodpasture's Syndrome- Hemoptysis, anemia, diffuse pulmonary infiltrates, glomerulonephritis. A form of anti-glomerular basement membrane nephritis. Differentiation from Wegener's- Wegener's: sinus involvement with nodular pulmonary changes. c. Systemic Lupus Erythematosis- A multisystem inflammatory disorder with autoantibody production. More frequent in young black women. 1) Clinical Manifestations- Dx. requires evidence of disease in more than one organ system in association with a disturbance in the immune system. skin: malar rash, discoid rash, photosensitivity. oral ulcers joints: arthritis lungs/heart: pleurositis or pericarditis kidneys: proteinuria or cellular casts CNS: seizures or psychosis hematologic: hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia immunologic: positive LE cell prep, anti-DNA, anti-Sm, false-positive VDRL (any one of the above) antinuclear antibody 2) Head and Neck Manifestations- larynx: thickening of the TVCs, limited excursion of the arytenoids, perichondritis and chondritis of the laryngeal and tracheal cartilages, cricoarytenoid and cricothyroid arthritis=> hoarseness, pain, possible obstruction; nose: nasal cavity dryness with frequent septal ulcers and eventual perforation anteriorly=> nasal crusting, intermittent epistaxis; oral cavity: superficial ulceration with surrounding erythema of the buccal mucosa or palate; ear: may produce autoimmune inner ear disease. 3) Treatment- nonsteroidal anti-inflammatory drugs, antimalarials, glucocorticoids, possibly azathioprine and cyclophosphamide. d. Sjogren's Syndrome- Systemic autoimmune disorder of the exocrine glands that may occur alone or in conjunction with a connective tissue disease. Diagnosis is based on the presence of two of the three hallmarks of the disease: xerostomia, keratoconjunctivitis sicca, and connective tissue disease. Most frequently occurs between 40-60 years of age. 9:1 female to male predominance. 1) Clinical Features- Predominant symptoms are those of ocular and oral dryness: grittiness, foreign body sensation, itching, photophobia, inability to produce tears, tenacious ocular secretions that accumulate overnight, painful tongue, severe dental caries. Signs: 1. Schirmer test- <5 mm wet=> abnormal (85% specific, 85% sensitive) 2. rose bengal staining is more specific=> filiform keratitis 3. labial minor salivary gland biopsy- 58% sensitive 4. parotid biopsy- 100% sensitive (according to Marx et al.) S/S beyond the head and neck- nonproductive cough, itching, dysphagia, dyspareunia, arthritis, gastric atrophy, glomerulonephritis, hypothyroidism, Raynaud's. 2) Lab- CBC (chronic normocytic normochromic anemia), + latex fixation, + ANA in 50-70% (absence of both SS-A and SS-B excludes Sjogren's syndrome). 3) Histopathology- lymphocytic infiltrates in exocrine gland tissue: may range from lymphoid hyperplasia to lymphoma (Non-Hodgkin's lymphoma 44x more common in this population). Clinical features associated with increased risk of lymphoma- parotid enlargement, splenomegaly, lymphadenopathy. 4) Treatment- symptomatic. e. Periarteritis Nodosa- fibrinoid necrosis of medium-sized arteries, kidneys commonly involved, nonspecific nasal mucosal lesions. f. Hypersensitivity Angiitis- a necrotizing leukocytoclastic vasculitis, usually secondary to a drug reaction. Present with purpuric papules and urticaria. g. Henoch-Schonlein Purpura- a hypersensitivity vasculitis with abdominal pain, purpura, arthralgia, and renal disease. h. Churg-Strauss Syndrome- hypereosinophilia plus allergic rhinitis and/or asthma plus a systemic vasculitis of medium and small muscular arteries. Prodrome- atopy, allergic rhinitis Second Phase- hypereosinophilia and eosinophilic tissue infiltration Final Phase- systemic necrotizing vasculitis 70% of patients will have nasal involvement with polyps, resulting obstructing, rhinorrhea, and crusting. Treatment- high dose corticosteroids, possibly cyclophosphamide. i. Behcet's Disease- Apthous ulceration of the upper aerodigestive tract and genitalia, ocular inflammation, cutaneous vasculitis. No known treatment. D. Foreign-Body Reaction 1. Cocaine-Induced Midline Granuloma- Produces ulceration of midline strictures of the upper respiratory tract (septum, nasopharynx, soft palate). Usually infected with Staph. aureus. Treatment- cessation of cocaine use, IV Abx. 2. Cholesterol Granuloma- Felt to arise secondary to inadequate ventilation, impaired drainage and hemorrhage, of the middle ear or paranasal sinuses. Cell breakdown occurs (be it erythrocyte, ME mucosa, transudate, or combination- exact source unknown), and cholesterol precipitates. The precipitate then elicits a foreign body-like reaction with neovascularization and formation of granulation tissue. a. Paranasal Sinuses- Produce nasal congestion, rhinorrhea, chronic frontal headaches, and diplopia with progressive exopthalmos. May produce pressure erosion of the sinus wall which may lead to orbital and/or intracranial extension. Majority, however, do NOT expand or cause bone destruction. CT will reveal a nonenhancing lesion of the same density as brain tissue. MRI shows increased signal intensity in both T1 and T2 weighted images. Treatment is that of radical removal and establishment of effective drainage of the affected sinuses. b. Temporal Bone- 80% with a history of TB in early childhood or in immediate family (Plester and Steinbach). Symptomatology of cholesterol granuloma is controversial. Some feel this lesion is asymptomatic and any symptoms that are present are attributable to an accompanying cholesteatoma. Others feel that this is an expansile lesion, with resultant cerebellopontine (V-VIII) involvement. Differentiation from cholesteatoma: cholesterol granuloma cholesteatoma contents: cholesterol crystals keratin lining: fibrous squamous CT: sharp, smooth margins sharp, smooth margin homogeneous density homogeneous density *isodense to brain *hypodense to brain *isodense to CSF no enhancement no enhancement Rx: permanent drainage route removal, exteriorize (via mastoid or ME if ET patent, via exteriorized mastoid cavity or Silverstein tube if not) 3. Gout- Arthritis of gout usually is episodic, self-limited, and monoarticular. One will see negatively-birefringent urate needles by microscopy. a. Head and Neck Manifestations (rare)- Two main processes: 1. gouty arthritis and 2. tophaceous deposits. 1) gouty arthritis- most common site in the H and N is the cricoarytenoid joint=> pain, dysphagia, hoarseness, aspiration, stridor, airway compromise (depending on the position of fixation). 2) tophus- classic H and N involvement is the helical rim of the external ear (usually asymptomatic), may also occur on the arytenoids, TVCs, cricoarytenoid joint, soft tissues, nasal septum. b. Treatment- colchicine or indomethacin for acute attacks, allopurinol prophylactically. 4. Others- silicone, silica, suture (especially silk, cotton, gut), starch (less reactive than talcum). E. Infectious Diseases 1. Bacterial a. Cat-Scratch Disease- 50% present with a head and neck mass. 1) Cause- intracellular pleomorphic, gram-negative, non-acid fast bacilli on Warthin-Starry silver stain. 2) Stages- early: reticular cell hyperplasia intermediate: granulomas late: microabscesses 3) Signs/Symptoms- tender regional adenopathy, mild fever, 55-94% with cutaneous lesion at the site of inoculation. 4) Diagnosis- 1. Hx cat exposure, 2. presence of primary inoculation site, 3. regional adenopathy, 4. histologic features of cat-scratch disease via excisional biopsy, 5. pleomorphic Warthin-Starry silver-staining intracellular bacilli, and 6. failure to demonstrate other causative agents. 5) Treatment- supportive, Abx ineffective, I+D if extensive abscess. 6) Prognosis- adenopathy will subside in 1-2 months. b. Brucellosis- Caused by aerobic gram-negative bacilli. Occurs in cattle, pigs, goats, elk, and bison. Acquired usually from butter from one of the aforementioned animals. Produces weakness, sweating, chills, malaise, H/A, backache, and arthralgia. Also causes granulomas. Fever highest in the afternoon. Diagnosis is by H+P and serum titers. Treatment- tetracycline. c. Rhinoscleroma- Caused by Klebsiella rhinoscleromatis. 1. Catarrhal stage: prolonged purulent rhinorrhea. 2. Granuloma stage: granulomatous nodules. 3. Cicatricial (sclerotic) stage: dense fibrotic reactions that stenose the nose, larynx, or tracheobronchial tree. May also have sinus, lacrimal gland, and cervical node involvement. Diagnosis: Patients with prolonged rhinorrhea, "honeycomb-color" crusting in the nose, Hx of travel to Central America or Eastern Europe, culture, vacuolated histiocyte (Mikulicz's cells). Treatment: streptomycin or tetracycline, dilatation if necessary. d. Leprosy (Hansen's disease) 1) Cause- Mycobacterium leprae via open ulcers of lepromatous skin, nasal discharge, or breast milk. 2) Clinical Manifestations- hypopigmented or erythematous macules, tuberculoid skin and nerve involvement with muscle wasting and anesthesia, anesthetic plaques, nerve thickening in the plaque vicinity, mucosal nodules in the mouth and nose that ulcerate (especially anterior inferior turbinate), keratitis, laryngeal ulcerations, lymphadenopathy, hyposmia, atrophy of the anterior maxillary spine and maxillary alveolar process, nasal collapse, fish-mouth deformity, facial nerve paralysis, eyebrow and eyelash loss. 3) Treatment- dapsone for life e. Nontuberculous Mycobacteria- Less virulent than TB and less responsive to standard antituberculous drugs. May colonize the upper respiratory tract- therefore, repeated positive cultures are more significant than a single culture. Occurs predominantly between 1-6 years of age. More common cause of cervical lymphadenopathy than TB. 1) Pathogenesis- Person-to-person transmission has never been documented. Usual source is soil to mouth or eye. Altered immune status is usually present. 2) Clinical Manifestations- Most common H+N site is the cornea (ulceration). Second most common site in H+N is cervical lymph nodes: usually unilateral, involving the anterior cervical, preauricular, and submandibular nodes most commonly. Nodes will be separate, discrete, arising quickly, adherent to overlying skin, rapidly progressing to abscess. 3) Diagnosis- Culture and sensitivity (takes 2-4 weeks for most species) of biopsy. Acid-fast staining. 58% of lymph nodes in children diagnosed as "granulomatous inflammation" grew mycobacteria on culture. R/O pulmonary involvement. Will have a negative or weakly positive PPD (10 mm wheal). 4) Treatment- excisional biopsy, antibiotic regimen based on susceptibility. I+D CONTRAINDICATED. f. Tuberculosis- (Scrofula is a nonspecific term, referring to tuberculous and/or nontuberculous cervical adenopathy.) Relatively rare in the H+N. After entry, 90% who have a positive PPD will be asymptomatic. May develop disease any time during life if left untreated. 1) Pathogenesis- Generally transmitted via inhalation of airborne droplets. Less commonly, via direct contact with an open wound. Organism: Mycobacterium tuberculosis. 2) Clinical Manifestations- Multiple. Some with constitutional symptoms. H+N manifestations include, most commonly, cervical lymphadenitis. Nodes will be multiple, matted, bilateral, firm, nontender (10% tender), and frequently involving the posterior triangles. Laryngeal involvement occurs in less than 2%, showing edema, granulomas or ulcerations, and possibly polypoid changes. The most common laryngeal site is the arytenoids. Laryngeal symptoms include cough, hoarseness, and weakened voice. Ocular involvement includes conjunctivitis, keratitis, and uveitis. Salivary gland involvement (diffuse glandular enlargement) occurs most commonly in the parotid. Oral cavity involvement (1.5%) presents with painful or painless ulcers, most frequently involving the tongue. Otologic involvement (rare) includes granulomas appearing as thickened, hyperemic spots which coalesce to form multiple TM perforations, which then painlessly drain a thin, watery discharge. Granulation tissue then increases, with discharge becoming thick and cheesy. Mastoiditis may ensue, with intracranial extension. Mastoid films typically show absence of bony destruction and sclerosis, since the process is relatively acute. 3) Diagnosis- positive PPD (greater than or equal to 10 mm), (98% with cervical lymphadenitis secondary to TB will have a + PPD). Always obtain a CXR. Consider excisional biopsy (obligated to biopsy if recently on antituberculous therapy). Avoid I+D. 4) Treatment- Antituberculous agents: Isoniazid 300 mg po qd plus rifampin 600 mg po qd for 9 months. Obtain LFTs monthly (according to Thawley et al). Lymph node excision(s) en bloc if fluctuant or chronically drain. Mastoidectomy for concurrent mastoiditis. g. Actinomycosis 1) Cause- Actinomyces species (anaerobic or microaerophilic). May follow dental manipulation or trauma. 2) Clinical Manifestations- May occur virtually anywhere in the H+N, with constitutional symptoms, trismus, and GI complaints. A palpable mass is the most common H+N finding. 61% will have a visible sinus tract, and 40% will have lymphadenopathy. Dental, sinus, and perimandibular disease is common. Will exhibit a characteristic purplish discoloration of the overlying skin. May cause granuloma formation and frank suppuration of the larynx=> pain, hoarseness, respiratory obstruction. 3) Diagnosis- Culture for 1-2 weeks in thioglycollate broth with a C02 atmosphere from FNA or curettage. Obtain panorex, facial films. Will see sulfur granules on histology. 4) Treatment- Surgical debridement + aqueous PCN G IV x 2-6 weeks (depending on the author). PCN-allergic: tetracycline or erythromycin. h. Syphilis 1) Cause- Treponema pallidum 2) Head and Neck Manifestations 1. incubation period: usually 3 weeks. 2. primary stage: primary chancre lesion at the site of initial inoculation (ex.- painless oral or laryngeal ulcerations), reactive lymphadenopathy. 3. secondary stage: (2-12 weeks after contact), white macules or papules on the oral mucosa, loss of eyelashes, localized alopecia, acute rhinitis, laryngitis, otitis media, pharyngitis, eruptions of the external ear, regional adenopathy, constitutional symptoms, meningitis. 4. latent stage: relatively asymptomatic, may have mucocutaneous relapses, 1/3=> complete remission, 1/3=> remain latent, 1/3=>tertiary stage. 5. tertiary stage: saddle deformity of the nose with nasoseptal or hard palate ulceration; granulomatous infiltration of the maxilla, mandible, tongue, larynx; osteomyelitis of the temporal bone; CN injury with vocal cord paralysis, dysphagia; SNHL, vertigo 6. congenital syphilis: frontal bossing, short maxilla, saddle nose, protruding mandible, high palatal arch, Hutchinson's incisors, mulberry molars, mental retardation, rhagades (radiating scars about the mouth), SNHL (same as with tertiary syphilis- sudden, bilateral, fluctuating, poor word discrimination), may have Tullio's and Hennebert's signs (not pathogneumonic). 3) Diagnosis- Darkfield examination. FTA-ABS positive whether patient has been treated or untreated. VDRL for screening. If positive VDRL, repeat. If still positive, obtain FTA-ABS. VDRL may be negative in tertiary syphilis. 4) Treatment- penicillin, possibly steroids for improvement of hearing and reduction of vestibular symptoms. i. Staphylococcus/Streptococcus j. Anthrax- Caused by gram positive rod Bacillus anthracis via direct contact from infected animals or material. 95% present with a small papule that progresses into a necrotic ulcer with surrounding edema (painless). Regional lymphadenopathy may be present. Diagnosis is by gram stain, culture, suspicious Hx. Treatment- PCN G. k. Tularemia- Caused by gram negative pleomorphic rod, Francisella tularensis. Reservoir: ticks, rabbits, deer. Spread via direct contact. Patient will exhibit skin ulcerations and granulomatous regional lymphadenopathy. The oculoglandular form presents with photophobia, decreased visual acuity, and cervical and preauricular lymphadenopathy. Exudative pharyngitis may also be present. Diagnosis is confirmed with a serum agglutination test. Treatment: streptomycin. l. Granuloma Inguinale- Caused by Calymmatobacterium granulomatis via sexual transmission. The most common nongenital site is the oral cavity: cicatricial lesion with extensive scarring and contracture. Diagnosis is by culture. Treatment is with tetracycline, ampicillin, or bactrim. 2. Fungal a. Histoplasmosis 1) Cause- Histoplasma capsulatum, most common in the Ohio and Mississippi River valleys, via airborne transmission. 2) Clinical Manifestations- 1. primary respiratory infection, 2. chronic pulmonary infection, and 3. progressive disseminated infection. Disseminated: granulomatous lesions of the lips, gingiva, tongue, pharynx, and larynx. These lesions show firm, slowly enlarging, painful ulcers with heaped-up edges or a verrucous appearance=> sore throat, painful mastication, hoarseness, gingival irritation, dysphagia, weight loss. 40-75% of adults and 18% of children exhibit oropharyngeal involvement. 3) Diagnosis- swab specimen from the center of the ulcer, with growth on Sabouraud's medium. 4) Treatment- amphotericin B. b. Blastomycosis 1) Cause- Blastomyces dermatitidis, airborne transmission 2) Clinical Manifestations- (oropharyngeal and laryngeal involvement much less common than in histoplasmosis). May range from being asymptomatic to acute pneumonitis with disseminated infection involving skin, bones, and the GU system. Lesions exhibit proliferative verrucous growth with scarring. A common triad is that of cutaneous disease + pulmonary involvement + constitutional symptoms. 3) Diagnosis- sputum culture on Sabouraud's medium, skin scrapings 4) Treatment- amphotericin B c. Coccidiomycosis- Caused by Coccidioides immitis. Endemic in the San Joaquin Valley of California. Manifestations rare in the head and neck. May involve the skin, mucus membranes, thyroid, eyes, trachea, salivary glands, and epiglottis. Lesions present as nodules or erosions. Diagnosis is by skin test and complement fixation. Treatment: amphotericin B. d. Candidiasis- Caused by Candida albicans. Predisposing factors- antibiotics, immunocompromise. Will present with creamy white patches of pseudomembrane=> odynophagia, dysphagia, angular cheilitis, and laryngitis. Diagnosis- clinical exam, culture on Saubouraud's medium. Treatment- nystatin, amphotericin B. e. Rhinosporidiosis- (strawberry lesions), caused by Rhinosporidium seeberi, especially prominent in Southern India and Sri Lanka, S/S: indolent, painless, warty excrescences (friable, red, polypoid lesions) of the nasal, palatal, and conjunctival mucus membranes. Treatment: excision. f. Phycomycosis 1) Cause- Mucor, Rhizopus, Absidia. Immunocompromise is a predisposing factor. 2) Clinical Manifestations- facial pain is the most common presenting symptom, fever, bloody rhinorrhea, facial swelling, edema, sinus tenderness, obtundation, CN palsies, visual loss, proptosis, black necrotic eschar on mucus membranes. 3) Diagnosis- biopsy (nonseptate hyphae), CT. 4) Treatment- amphotericin B, aggressive surgical debridement. g. Cryptococcosis- Caused by Cryptococcus neoformans. Immunosuppression is a predisposing factor. Rare in the H+N. May have membranous nasopharyngitis, meningitis, hearing loss. Diagnosis is by fluorescent antibody. Treatment with amphotericin B. h. Aspergillosis- forms: allergic, noninvasive, invasive. 1) Cause- Aspergillus fumigatus (Invasive form usually occurs only in an immunocompromised host.) 2) Clinical Manifestations- tenacious, thick, dark secretions; facial hypesthesia, ophthalmoplegia, proptosis, visual loss in the invasive form. Characteristic single sinus involvement in the noninvasive form. May be distinguished from phycomycoses by microscopic exam (septate, bifurcating hyphae with Aspergillus) and culture. Invasive form causes bony destruction and calcifications on CT. Treatment is by surgery and if invasive, amphotericin B. 3. Parasitic a. Leishmaniasis- Transmitted by the bite of the sandfly. 1) Cutaneous Leishmaniasis- Most frequent on the extremities. H+N involvement does occur. Papules=> ulceration and encrustation (1-3 cm). Diagnosis is by biopsy. Treatment is with pentostam (obtained from the C.D.C.). 2) Mucocutaneous Leishmaniasis- Also called Espundia. The initial lesion is usually on the extremity, with blood-borne spread to the mucus membranes of the OC/OP. Months to years later, progressive inflammation and destruction of the soft tissue of the mouth and soft tissue and cartilage of the nose. Diagnosis is by biopsy. Treatment with pentostam. b. Myiasis- Nonfuruncular and furuncular forms. Via screwworm flies. May involve the nasopharynx in the former and the skin in the latter. Diagnosis is by microscopic exam. Treatment with surgical debridement. c. Toxoplasmosis- Majority asymptomatic. Infection occurs by ingestion of oocyst-containing cat feces or infected poorly cooked lamb or pork. Clinically overt disease may present in almost any organ system- lymphatics being most common. Liver, eyes (choreoretinitis), and CNS may be involved. Diagnosis is by IgM (acute phase), four-fold increase in IgG (acute phase). Treatment with pyrimethamine plus trisulfapyrimidines. F. Traumatically-Induced Disorders 1. Intubation Granuloma- Almost invariably involves the vocal process of the arytenoid. Occurs only in adults! 75% female. Progression: contact ulcer=> granuloma=> pedunculated polyp. Symptoms of hoarseness and foreign body sensation predominate. Treatment- antibiotics for secondary infection, voice rest, observation (unless pedunculated, then excision). 2. Reparative Granuloma- Etiology unknown, but felt to be secondary to local trauma. May be seen following tooth removal. Types- 1. peripheral: sessile or pedunculated mucosa-covered reddish or bluish mass arising from the gingiva or alveolar mucosa, most common on the anterior mandible. 2. central: endosteal lesion, usually anterior to the first molar in the mandible, radiographically will appear as a lytic, expansile, unilocular cavity with well-demarcated, non-sclerotic margins; the bony cortex will be thinned but intact. Treatment- curettage. 3. "Pyogenic Granuloma"- Nonspecific term for granulation tissue secondary to minor trauma with secondary infection. Most frequent on the gingiva. Lesion- elevated, pedunculated or sessile, smooth or verrucal, painless, soft. Treatment- excision. (Remember that lobular capillary hemangima is also referred to as pyogenic granuloma.) ------------------------------------------------------------------------------- Bibliography Boscia, R., and Knox, R.D. Resident's Page, Archives of Otolaryngology-Head and Neck Surgery, 116, 2/90, pg. 225-227. Benjamin, D.R. Granulomatous Lymphadenitis in Children. Archives of Pathology and Laboratory Medicine, 111, 8/87, pg. 750-753. Deital, M., et al. Modern Management of Cervical Scrofula. Head and Neck, 1-2/89, pg. 60-66. Gates, G.A., editor. Current Therapy in Otolaryngology-Head and Neck Surgery- 3, B.C. Decker, 1987, pg. 289-290. Kornblut, A.D., editor. Granulomatous Disorders of the Head and Neck, Otolaryngology Clinics of North America, 15:3, August 1982, pg. 471-703. Thawley, S.E., et al, editors. Comprehensive Management of Head and Neck Tumors, W.B. Saunders Co., 1987. Cummings, C.W., et al, editors. Otolaryngology-Head and Neck Surgery, C.V. Mosby Co., 1986. Ophir, D., et al. 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