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Ulcerated tumor mass involving the right base of the tongue
CLINICOPATHOLOGIC CONFERENCE
Editor: Steven D. Vincent
Ulcerated tumor mass involving the right base of the tongue Nadarajah Vigneswaran, BDS, DrMedDent, a Ken R. Tilashalski, DMD, b Glenn E. Peters, MD, c Vishnu V.B. Reddy, MD, d and Brad K. Rodu, DDS, e Birmingham, Ala. UNIVERSITY OF ALABAMA AT BIRMINGHAM
CLINICAL PRESENTATION In January 1995, a 78-year-old white woman was referred to the Otolaryngology and Head and Neck Surgery Clinic, University of Alabama at Birmingham for evaluation and management of an ulcerated tumor on the right base of the tongue. The patient also complained of a sore throat, mild dysphagia, and bilateral otalgia of 2 months duration. During this time, the patient lost approximately 25 pounds and was hospitalized for acute labyrinthitis and mild dehydration. Review of the hospital records indicated that the patient had fevers that spiked each evening around 6:00 PM to 101°F. The patient also gave a history of nocturnal sweating. The patient's medical history was significant for hypertension, peripheral vascular insufficiency, chronic vertigo, degenerative joint disease, hiatal hernia, and mitral valve prolapse. The patient also had chronic bronchitis and coughed brownish sputum on a daily basis. Her medications included Procardia XL; Propulsid; Antivert; Trental; K-Dur; Relafen; Darvocet; and Augmentin. The patient was allergic to sulfa-containing drugs. The patient's mother and her daughter reportedly had a history of cancer (type unknown). The patient denied the use of tobacco and alcohol at any point in her life. On examination the patient presented with stable vital signs and was in no acute distress. Extraoral examination revealed a fight level II cervical lymph node that was firm and enlarged. On intraoral examination a 3 x 4 cm reddish-gray, ulcerated, firm exophytic mass was noted in the fight posteriolateral base of the tongue (Fig. 1). The inferior margin of this lesion extended along the superior aspect of the pharyngoepiglottic fold. The patient underwent contrast enhanced computed tomogaInstructor, Department of Diagnostic Sciences, School of Dentistry. bAssistant Professor, Department of Diagnostic Sciences, School of Dentistry. Cprofessor, Division of Otolaryngology/Head and Neck Surgery, School of Medicine. dAssociate Professor, Department of Pathology, School of Medicine. ~Professor, Department of Diagnostic Sciences, School of Dentistry. Accepted for publication Sept. 10. 1996. Copyright © 1997 by Mosby-Year Book, Inc. 1079-2104/97/$5.00 + 0 7/14/78007
Fig. 1. Clinical photograph shows ulcerated exophytic tumor involving right base of tongue.
raphy (CT) scan of the neck, thorax, and abdomen. The head and neck scan revealed a 3 x 1 cm mass involving the base of the tongue with extension into the right oropharynx (Fig. 2). Multiple enlarged lymph nodes, 1 to 2 cm in diameter, were detected in the neck bilaterally and in the anterior mediastinal region. No evidence of disease was noted below the diaphragm. An incisional biopsy and fine needle aspiration of the lesion was performed and submitted for histopathologic examination.
DIFFERENTIAL DIAGNOSIS The clinical presentation of this tumor with cervical lymph node involvement strongly suggests a malignant process. On the basis of the clinical presentation and the age of the patient, squamous cell carcinoma heads the list of differential diagnoses. Almost 90% of intraoral malignant tumors found in this age group are primary squamous cell carcinomas. 1 However, it should be noted that this patient did not have any risk factors for oral cancer such as smoking and alcohol consumption. 2 Because of the close proximity of this tumor to the lingual tonsil and the involvement of cervical lymph nodes, the possibility of a lymphoma is also a consideration. The presence of this tumor in combination with cervical lymphadenopathy and symptoms of recent weight loss and multiple episodes of fever and night 46/
462
Vigneswaran et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY November 1997
Fig. 3. Incisional biopsy of tumor demonstrates mixed cellularity Hodgkin's disease with a number of mononuclear and multilobated variants of Reed-Sternberg cells. (Hematoxylineosin stain; original magnification x200.)
Fig. 2. CT scan illustrates soft tissue mass arising from right base of tongue. sweats suggests the possibility of Hodgkin's disease. Although only 1% of all malignant conditions found in the oral cavity are metastases, the multifocal presentation is consistent with metastatic carcinoma from a distant site. Gingiva, tongue, and palate are the favored intraoral sites for metastatic carcinoma) Kidney, lung, breast, and skin represent the most common sites of primary malignancies that produce intraoral metastases. 3 The differential diagnosis also includes a malignant salivary gland tumor and nasopharyngeal carcinoma. However, a rapid growth rate with cervical node involvement is not a feature associated with intraoral malignant salivary gland tumors. Instead these lesions most often demonstrate slow locally invasive growth and late metastatic spread. Mucoepidermoid carcinomas and adenoid cystic carcinomas are the most common intraoral malignant salivary gland tumors. 4 They occur most commonly in the palate; the base of the tongue is an unusual site. 4 Nasopharyngeal carcinoma, which tends to show early metastatic spread to cervical lymph nodes, occurs commonly in the lateral and posteriorsuperior wall of the nasopharynx. 5 Again, involvement of the base of the tongue is rarely reported: 5 Considering the rapid growth of the tumor and t h e patient's age, a melanoma (primary or metastatic) or an aggressive soft tissue sarcoma should be included in the differential diagnosis. The patient's symptoms, such as multiple bouts of recurrent fever, weight loss, and night sweats may be seen with infectious diseases
such as tuberculosis or deep fungal infections. However, the size, rapid growth rate, and widespread nodal involvement make an infectious cause of this lesion highly unlikely.
DIAGNOSIS Histologic sections of the incisional biopsy revealed aggregates of lymphoid tissue covered by nonkeratinizing stratified squamous epithelium compatible with tonsillar tissue. In most areas tonsillar architecture was replaced by a mixed cellular population consisting of lymphocytes, plasma cells, histiocytes, eosinophils, and a few neutrophils (Fig. 3). Among this mixed cellular population were numerous large atypical mononuclear cells with indistinct cell borders. These cells had a markedly indented vesicular nucleus with hyperchromatic macronucleoli (Fig. 4). A few typical bilobed Reed-Steinberg cells and their varients with multilobated nuclei were also noted (Fig. 4). Cytologic examination from needle aspiration revealed a similar cell population. Large atypical mononuclear cells and Reed-Sternberg cells were positive for Ki-1 (Ber-H2; CD30) antigen and were negative for Leu M1 (CD15) antigen. Immunoreactivity for either keratin or leukocyte common antigen (CD45) was not detected in these large atypical neoplastic cells. Immunoreactivity for T-cells (UCHL1; CD45RO) and B-cells (L26; CD20) was noted among the small reactive lymphocytes, but the large atypical cells were not reactive with either T- or Bcell specific antibodies. FINAL DIAGNOSIS AND STAGING Hodgkin's lymphoma; mixed cellular type; stage IIB.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
Vigneswaran et al. 463
Volume 84, Number 5
MANAGEMENT Considering the presence of the "constitutional" or "B" symptoms and the involvement of multiple lymph nodes above the diaphragm, multiagent chemotherapy consisting of ABVD (doxombicin, bleomycin, vinblastine, and decarbazine) was planned. However before initiation of chemotherapy the patient died from complications of the disease 2 weeks after the initial diagnosis. DISCUSSION Waldeyer's ring represents the second most common site for extranodal lymphomas after the gastrointestinal tract. 6 The majority of Waldeyer's ring lymphomas are high-grade B-cell lymphomas of centroblastic type. 7 Hodgkin's disease involving the Waldeyer's ring is rare, representing 1% to 3.7% of lymphomas in this site. a, 9 According to previously reported cases, Hodgkin's lymphomas Occur in the nasopharynx or tonsil with equal frequency and rarely involve the base of the tongue, s, 9 Thus the present case represents an unusual presentation of primary Hodgkin's lymphoma involving tonsillar tissue at the base of the tongue. Hodgkin's disease primarily affects patients between the ages of 15 and 40, with far fewer patients over the age of 50, as in the current case. 1° The most common presenting symptom of Hodgkin's disease is an enlarged cervical lymph node (>2 cm) that is firm, mobile, and "rubbery," not rock-hard and fixed as described with metastatic carcinomas. Hodgkin's disease frequently involves mediastinal and hilar lymph nodes, whereas only about 15% of patients have subdiaphragmatic disease. 1° Hodgkin's disease may also involve visceral sites such as spleen, liver, and bone marrow, l° As in the present case Hodgkin's disease is not infrequently associated with symptoms such as unexplained fever, night sweats, and loss of more than 10% of body weight, l° These symptoms, known as "constitutional" or "B" symptoms may indicate poor prognosis, which is taken into consideration during staging and treatment planning. 1° Although the cause of Hodgkin's disease is still unknown, recent reports have implicated the EpsteinBarr virus (EBV) as a possible cause in sinonasal and Waldeyer's ring Hodgkin's lymphoma. 9 Association of EBV with Hodgkin's lymphomas was supported by detecting EBV latent membrane protein (LMP) and EBV encoded RNA (EBER1) in the neoplastic ReedSteruberg cells. 9 There is also a genetic susceptibility on the basis of a close relationship between certain types of human leukocyte antigens (HLA) and Hodgkin's disease.11 Diagnostic confirmation of Hodgkin's disease can be only made after histopathologic examination of tissue, preferably from a lymph node. The diagnostic
Fig. 4. High-power view of tissue section depicts classic Reed-Sternberg cells with mirror-image bilobated nucleus containing prominent nucleoli. (Original magnification x600.) malignant cells, known as Reed-Sternberg cells, are large and consist of multilobated nuclei with prominent pink nucleoli. This cell population most often constitutes less than 1% of the cellular infiltrate whereas the remaining cells, composed of lymphocytes, plasma cells, eosinophils and neutrophils are reactive in nature. Reed-Sternberg cells and variants exhibit a complex array of immunophenotypes.9, 10 However the expression of lymphoid activation (CD30:Ki-1; Ber-H2) and granulocyte (CD15:LeuM1) markers and the lack of common leukocyte antigen (CD45) are diagnostic for the Reed-Sternberg cell and its variants. 9, t0 The four major histopathologic types of Hodgkin's disease are lymphocyte predominant, lymphocyte depletion, mixed cellularity, and nodular sclerosis, with the latter two types accounting for 90% of all cases. I° Although in the past histologic subtypes carried very different prognoses, with modern treatment these differences have become insignificant. 1° The treatment of choice for Hodgkin's disease is dictated by the extent of disease involvement (staging) and the presence of any associated adverse prognostic factors (i.e., B symptoms), t° Localized Hodgkin's disease without any adverse prognostic factors can be treated with radiotherapy, leading to a cure rate of 60% to 90%. l° Chemotherapy is the mainstay of treatment for advanced and recurrent Hodgkin's disease and has a cure rate of 50% to 70%. l° The most commonly used chemotherapy regimens for Hodgkin's disease are MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and decarbazine) or a combination of both MOPP and ABVD. 1° REFERENCES
1. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and
464 Vigneswaran et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
November 1997
2. 3. 4.
5. 6. 7. 8.
maxillofacial pathology. Philadelphia: WB Saunders; 1995. p. 259-321. Blot WJ, McLaughlin JK, Winn DM, Austin DF, Greenberg RS, Preston-Martin S, et al. Smoking and drinking in relation to oral pharyngeal cancer. Cancer Res 1988;48:3282-7. Hirshberg A, Leibovich R Buchner A. Metastases to the oral mucosa: analysis of 157 cases. J Oral Pathol Med 1993;22:385-90. Auclair PL, Ellis GL, Gnepp DR, Wenig BM, Janney CG. Salivary gland neoplasms: general consideration. In: Ellis GL, Auclair PL, Gnepp DR, editors. Surgical pathology of salivary glands. Philadelphia: WB Saunders; 1991. p. 135-64. Dickson RI. Nasopharyngeal carcinoma: an evaluation of 209 patients. Laryngoscope 1981;91:333-54. Wright DH. Lymphomas of Waldeyer's ring. Histopathology 1994;24:97-9. Menargez J, Mollejo M, Carrion R, et al. Waldeyer ring lymphomas: a clinicopathologic study of 79 cases. Histopathology 1994;24:13-22. Todd GB, Michaels L. Hodgkin's disease involving Waldeyer's lymphoid ring. Cancer 1974;34:1769-78.
9. Kapadia SB, Roman LN, Kingma DW, Jaffe ES, Frizzera G. Hodgkin's disease of Waldeyer's ring: clinical and histoimmunophenotypic findings and association with Epstein-Barr virus in 16 cases. Am J Surg Pathol 1995;19:1431-9. 10. Miller TP, Grogan TM. Hodgkin's disease and non-Hodgkin's lymphoma. In: Stein JH, editor. Internal medicine. 4th ed. St. Louis: Mosby; 1994. p. 899-911. 11. Oza AM, Tonks S, Lim J, Fleetwood MA, Lister TA, Bodmer JG. A clinical and epidemiological study of human leukocyte antigen-DPB alleles in Hodgkin's disease. Cancer Res 1994;54: 5101-5.
Reprint requests: Nadarajah Vigneswaran, BDS, DrMedDent Department of Diagnostic Sciences, School of Dentistry University of Alabama at Birmingham Birmingham, Alabama 35294
Editor: Steven D. Vincent
Ulcerated tumor mass involving the right base of the tongue Nadarajah Vigneswaran, BDS, DrMedDent, a Ken R. Tilashalski, DMD, b Glenn E. Peters, MD, c Vishnu V.B. Reddy, MD, d and Brad K. Rodu, DDS, e Birmingham, Ala. UNIVERSITY OF ALABAMA AT BIRMINGHAM
CLINICAL PRESENTATION In January 1995, a 78-year-old white woman was referred to the Otolaryngology and Head and Neck Surgery Clinic, University of Alabama at Birmingham for evaluation and management of an ulcerated tumor on the right base of the tongue. The patient also complained of a sore throat, mild dysphagia, and bilateral otalgia of 2 months duration. During this time, the patient lost approximately 25 pounds and was hospitalized for acute labyrinthitis and mild dehydration. Review of the hospital records indicated that the patient had fevers that spiked each evening around 6:00 PM to 101°F. The patient also gave a history of nocturnal sweating. The patient's medical history was significant for hypertension, peripheral vascular insufficiency, chronic vertigo, degenerative joint disease, hiatal hernia, and mitral valve prolapse. The patient also had chronic bronchitis and coughed brownish sputum on a daily basis. Her medications included Procardia XL; Propulsid; Antivert; Trental; K-Dur; Relafen; Darvocet; and Augmentin. The patient was allergic to sulfa-containing drugs. The patient's mother and her daughter reportedly had a history of cancer (type unknown). The patient denied the use of tobacco and alcohol at any point in her life. On examination the patient presented with stable vital signs and was in no acute distress. Extraoral examination revealed a fight level II cervical lymph node that was firm and enlarged. On intraoral examination a 3 x 4 cm reddish-gray, ulcerated, firm exophytic mass was noted in the fight posteriolateral base of the tongue (Fig. 1). The inferior margin of this lesion extended along the superior aspect of the pharyngoepiglottic fold. The patient underwent contrast enhanced computed tomogaInstructor, Department of Diagnostic Sciences, School of Dentistry. bAssistant Professor, Department of Diagnostic Sciences, School of Dentistry. Cprofessor, Division of Otolaryngology/Head and Neck Surgery, School of Medicine. dAssociate Professor, Department of Pathology, School of Medicine. ~Professor, Department of Diagnostic Sciences, School of Dentistry. Accepted for publication Sept. 10. 1996. Copyright © 1997 by Mosby-Year Book, Inc. 1079-2104/97/$5.00 + 0 7/14/78007
Fig. 1. Clinical photograph shows ulcerated exophytic tumor involving right base of tongue.
raphy (CT) scan of the neck, thorax, and abdomen. The head and neck scan revealed a 3 x 1 cm mass involving the base of the tongue with extension into the right oropharynx (Fig. 2). Multiple enlarged lymph nodes, 1 to 2 cm in diameter, were detected in the neck bilaterally and in the anterior mediastinal region. No evidence of disease was noted below the diaphragm. An incisional biopsy and fine needle aspiration of the lesion was performed and submitted for histopathologic examination.
DIFFERENTIAL DIAGNOSIS The clinical presentation of this tumor with cervical lymph node involvement strongly suggests a malignant process. On the basis of the clinical presentation and the age of the patient, squamous cell carcinoma heads the list of differential diagnoses. Almost 90% of intraoral malignant tumors found in this age group are primary squamous cell carcinomas. 1 However, it should be noted that this patient did not have any risk factors for oral cancer such as smoking and alcohol consumption. 2 Because of the close proximity of this tumor to the lingual tonsil and the involvement of cervical lymph nodes, the possibility of a lymphoma is also a consideration. The presence of this tumor in combination with cervical lymphadenopathy and symptoms of recent weight loss and multiple episodes of fever and night 46/
462
Vigneswaran et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY November 1997
Fig. 3. Incisional biopsy of tumor demonstrates mixed cellularity Hodgkin's disease with a number of mononuclear and multilobated variants of Reed-Sternberg cells. (Hematoxylineosin stain; original magnification x200.)
Fig. 2. CT scan illustrates soft tissue mass arising from right base of tongue. sweats suggests the possibility of Hodgkin's disease. Although only 1% of all malignant conditions found in the oral cavity are metastases, the multifocal presentation is consistent with metastatic carcinoma from a distant site. Gingiva, tongue, and palate are the favored intraoral sites for metastatic carcinoma) Kidney, lung, breast, and skin represent the most common sites of primary malignancies that produce intraoral metastases. 3 The differential diagnosis also includes a malignant salivary gland tumor and nasopharyngeal carcinoma. However, a rapid growth rate with cervical node involvement is not a feature associated with intraoral malignant salivary gland tumors. Instead these lesions most often demonstrate slow locally invasive growth and late metastatic spread. Mucoepidermoid carcinomas and adenoid cystic carcinomas are the most common intraoral malignant salivary gland tumors. 4 They occur most commonly in the palate; the base of the tongue is an unusual site. 4 Nasopharyngeal carcinoma, which tends to show early metastatic spread to cervical lymph nodes, occurs commonly in the lateral and posteriorsuperior wall of the nasopharynx. 5 Again, involvement of the base of the tongue is rarely reported: 5 Considering the rapid growth of the tumor and t h e patient's age, a melanoma (primary or metastatic) or an aggressive soft tissue sarcoma should be included in the differential diagnosis. The patient's symptoms, such as multiple bouts of recurrent fever, weight loss, and night sweats may be seen with infectious diseases
such as tuberculosis or deep fungal infections. However, the size, rapid growth rate, and widespread nodal involvement make an infectious cause of this lesion highly unlikely.
DIAGNOSIS Histologic sections of the incisional biopsy revealed aggregates of lymphoid tissue covered by nonkeratinizing stratified squamous epithelium compatible with tonsillar tissue. In most areas tonsillar architecture was replaced by a mixed cellular population consisting of lymphocytes, plasma cells, histiocytes, eosinophils, and a few neutrophils (Fig. 3). Among this mixed cellular population were numerous large atypical mononuclear cells with indistinct cell borders. These cells had a markedly indented vesicular nucleus with hyperchromatic macronucleoli (Fig. 4). A few typical bilobed Reed-Steinberg cells and their varients with multilobated nuclei were also noted (Fig. 4). Cytologic examination from needle aspiration revealed a similar cell population. Large atypical mononuclear cells and Reed-Sternberg cells were positive for Ki-1 (Ber-H2; CD30) antigen and were negative for Leu M1 (CD15) antigen. Immunoreactivity for either keratin or leukocyte common antigen (CD45) was not detected in these large atypical neoplastic cells. Immunoreactivity for T-cells (UCHL1; CD45RO) and B-cells (L26; CD20) was noted among the small reactive lymphocytes, but the large atypical cells were not reactive with either T- or Bcell specific antibodies. FINAL DIAGNOSIS AND STAGING Hodgkin's lymphoma; mixed cellular type; stage IIB.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
Vigneswaran et al. 463
Volume 84, Number 5
MANAGEMENT Considering the presence of the "constitutional" or "B" symptoms and the involvement of multiple lymph nodes above the diaphragm, multiagent chemotherapy consisting of ABVD (doxombicin, bleomycin, vinblastine, and decarbazine) was planned. However before initiation of chemotherapy the patient died from complications of the disease 2 weeks after the initial diagnosis. DISCUSSION Waldeyer's ring represents the second most common site for extranodal lymphomas after the gastrointestinal tract. 6 The majority of Waldeyer's ring lymphomas are high-grade B-cell lymphomas of centroblastic type. 7 Hodgkin's disease involving the Waldeyer's ring is rare, representing 1% to 3.7% of lymphomas in this site. a, 9 According to previously reported cases, Hodgkin's lymphomas Occur in the nasopharynx or tonsil with equal frequency and rarely involve the base of the tongue, s, 9 Thus the present case represents an unusual presentation of primary Hodgkin's lymphoma involving tonsillar tissue at the base of the tongue. Hodgkin's disease primarily affects patients between the ages of 15 and 40, with far fewer patients over the age of 50, as in the current case. 1° The most common presenting symptom of Hodgkin's disease is an enlarged cervical lymph node (>2 cm) that is firm, mobile, and "rubbery," not rock-hard and fixed as described with metastatic carcinomas. Hodgkin's disease frequently involves mediastinal and hilar lymph nodes, whereas only about 15% of patients have subdiaphragmatic disease. 1° Hodgkin's disease may also involve visceral sites such as spleen, liver, and bone marrow, l° As in the present case Hodgkin's disease is not infrequently associated with symptoms such as unexplained fever, night sweats, and loss of more than 10% of body weight, l° These symptoms, known as "constitutional" or "B" symptoms may indicate poor prognosis, which is taken into consideration during staging and treatment planning. 1° Although the cause of Hodgkin's disease is still unknown, recent reports have implicated the EpsteinBarr virus (EBV) as a possible cause in sinonasal and Waldeyer's ring Hodgkin's lymphoma. 9 Association of EBV with Hodgkin's lymphomas was supported by detecting EBV latent membrane protein (LMP) and EBV encoded RNA (EBER1) in the neoplastic ReedSteruberg cells. 9 There is also a genetic susceptibility on the basis of a close relationship between certain types of human leukocyte antigens (HLA) and Hodgkin's disease.11 Diagnostic confirmation of Hodgkin's disease can be only made after histopathologic examination of tissue, preferably from a lymph node. The diagnostic
Fig. 4. High-power view of tissue section depicts classic Reed-Sternberg cells with mirror-image bilobated nucleus containing prominent nucleoli. (Original magnification x600.) malignant cells, known as Reed-Sternberg cells, are large and consist of multilobated nuclei with prominent pink nucleoli. This cell population most often constitutes less than 1% of the cellular infiltrate whereas the remaining cells, composed of lymphocytes, plasma cells, eosinophils and neutrophils are reactive in nature. Reed-Sternberg cells and variants exhibit a complex array of immunophenotypes.9, 10 However the expression of lymphoid activation (CD30:Ki-1; Ber-H2) and granulocyte (CD15:LeuM1) markers and the lack of common leukocyte antigen (CD45) are diagnostic for the Reed-Sternberg cell and its variants. 9, t0 The four major histopathologic types of Hodgkin's disease are lymphocyte predominant, lymphocyte depletion, mixed cellularity, and nodular sclerosis, with the latter two types accounting for 90% of all cases. I° Although in the past histologic subtypes carried very different prognoses, with modern treatment these differences have become insignificant. 1° The treatment of choice for Hodgkin's disease is dictated by the extent of disease involvement (staging) and the presence of any associated adverse prognostic factors (i.e., B symptoms), t° Localized Hodgkin's disease without any adverse prognostic factors can be treated with radiotherapy, leading to a cure rate of 60% to 90%. l° Chemotherapy is the mainstay of treatment for advanced and recurrent Hodgkin's disease and has a cure rate of 50% to 70%. l° The most commonly used chemotherapy regimens for Hodgkin's disease are MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and decarbazine) or a combination of both MOPP and ABVD. 1° REFERENCES
1. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and
464 Vigneswaran et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
November 1997
2. 3. 4.
5. 6. 7. 8.
maxillofacial pathology. Philadelphia: WB Saunders; 1995. p. 259-321. Blot WJ, McLaughlin JK, Winn DM, Austin DF, Greenberg RS, Preston-Martin S, et al. Smoking and drinking in relation to oral pharyngeal cancer. Cancer Res 1988;48:3282-7. Hirshberg A, Leibovich R Buchner A. Metastases to the oral mucosa: analysis of 157 cases. J Oral Pathol Med 1993;22:385-90. Auclair PL, Ellis GL, Gnepp DR, Wenig BM, Janney CG. Salivary gland neoplasms: general consideration. In: Ellis GL, Auclair PL, Gnepp DR, editors. Surgical pathology of salivary glands. Philadelphia: WB Saunders; 1991. p. 135-64. Dickson RI. Nasopharyngeal carcinoma: an evaluation of 209 patients. Laryngoscope 1981;91:333-54. Wright DH. Lymphomas of Waldeyer's ring. Histopathology 1994;24:97-9. Menargez J, Mollejo M, Carrion R, et al. Waldeyer ring lymphomas: a clinicopathologic study of 79 cases. Histopathology 1994;24:13-22. Todd GB, Michaels L. Hodgkin's disease involving Waldeyer's lymphoid ring. Cancer 1974;34:1769-78.
9. Kapadia SB, Roman LN, Kingma DW, Jaffe ES, Frizzera G. Hodgkin's disease of Waldeyer's ring: clinical and histoimmunophenotypic findings and association with Epstein-Barr virus in 16 cases. Am J Surg Pathol 1995;19:1431-9. 10. Miller TP, Grogan TM. Hodgkin's disease and non-Hodgkin's lymphoma. In: Stein JH, editor. Internal medicine. 4th ed. St. Louis: Mosby; 1994. p. 899-911. 11. Oza AM, Tonks S, Lim J, Fleetwood MA, Lister TA, Bodmer JG. A clinical and epidemiological study of human leukocyte antigen-DPB alleles in Hodgkin's disease. Cancer Res 1994;54: 5101-5.
Reprint requests: Nadarajah Vigneswaran, BDS, DrMedDent Department of Diagnostic Sciences, School of Dentistry University of Alabama at Birmingham Birmingham, Alabama 35294