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The otolaryngologic manifestations of malignant lymphoma with a high content of epithelioid histiocytes (Lennert's lymphoma)
12. Crysdale, W. S., and Stone, H. E.: Secondary neuroblastoma of the sphenoid sinus. J. Laryngol. Otol., 90:703705, 1976. 13. Cole, T. B., and McCoy, G.: Congenital cholesteatoma of temporal bone and sphenoid sinus. Arch. Otolaryngal., 87:576-579, 1968. 14. Mikaelian, D., et al.: Primary osteoma of the sphenoid sinus. Laryngoscope, 86:728-733, 1976. 15. Edison, B.: Primary inverting papilloma of the sphenoid
sinus. Trans. Am. Acad. Ophthalmol. Otolaryngol., 80:434-437, 1975. 16. Wyllie, J. W., III, Kern, E. B., and Djalilian, M.: Isolated sphenoid sinus lesions. Laryngoscope, 83:1252-1265, 1973.
Volume 1 Number 3 May 1980
Department of Otolaryngology, 727A University of California School of Medicine San Francisco, California 04143 (Dr. Ross)
The Otolaryngologic Manifestations of Malignant Lymphoma with a High Content of Epithelioid Histiocytes (Lennert's Lymphoma) LAUREN D. HOLINGER, M.D.,*
STEVEN F. SOLTES, M.D.,t PELLETTIERE, II, M.D.,~
EDMUND V,
DINO S. DELICATA, M.D.,§ AND ANANTHA I(. MURTHY, M.D.]I
Malignant lymphoma with a high content of epithelioid histiocytes is a rare nonHodgkin lymphoma first described by Lennert and Mestdagh (Lennert's lymphoma) in 1968. Distinguishing characteristics include frequent involvement of the nasopharynx, Waldeyer's ring, and cervical lymph nodes. Of the four patients included in this report, three had Waldeyer's ring involvement and four had cervical lymphadenopathy. Our experience and that of others demonstrate the unpredictable and variable course of the disease, as well as the inconsistent response to various therapeutic modalities; especially interesting is the remission obtained in one patient treated with corticosteroids alone, in contrast to the others who followed a rapid downhill course to death in spite of (or as a complication of) chemotherapy and radiation. The role of the otolaryngologist in the diagnosis and management of the disease is emphasized.
Accepted for publication December 12, 1979. *Assistant Professor, Department of Otolaryngology and Bronchoesophagology, Rush Medical College. Assistant Attending Physician, Rush-Presbyterian-St. Luke's Medical Center. Active Attending Physician, Children's Memorial Hospital. Clinical Staff, University of Illinois Eye and Ear Infirmary, Chicago, Illinois. tClinical Instructor, Department of Otolaryngology and Bronchoesophagology, University of Illinois Eye and Ear Infirmary, Chicago, Illinois. ¢Assistant Professor, Department of Pathology, Rush Medical College. Associate Attending Physician, Rush-PresbyterianSt. Luke's Medical Center, Chicago, Illinois. §Instructor, Department of Otolaryngology and Bronchoesophagalogy, Rush Medical College. Clinical Staff, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois. 1~4ssistant Professor, Department of Therapeutic Radiology, Rush Medical College. Clinical Staff, Rush-Presbyterian-St. Luke's Medical Center and Swedish Covenant Hospital, Chicago, Illinois. American Journal of Otalaryngology --Volume 1, Number 3, May 1980
229
American Journal of
Otolaryngology
Malignant lymphoma with a high content of epithelioid histiocytes (MLEH) is a non-Hodgkin lymphoma' first described by Lennert and Mestdagh (Lennert's lymphoma) in 1968. 2 Although this relatively recently described and rare disease has been documented in the literature of several disciplines, 3-~to date there have been no reports in the otolaryngologic and head and neck literature, despite the fact that distinguishing features include a high frequency of involvement of the nasopharynx, Waldeyer's ring, and cervical lymph nodes. MLEH is most commonly seen in the middle aged or elderly, and the symptoms of lymphadenopathy, hepatomegaly, and splenomegaly are relatively frequent. 2,s" 7 The entity produces a distinctive histologic pattern characterized by a high number of epithelioid cells and an absence of Dorothy Reed-Sternberg cells. 2 Lennert's original 30 cases illustrated the frequent tonsillar involvement (five of 30).2 Burke and Butler' presented 15 cases in which they described a predilection for Waldeyer's ring involvement (three of 15). Since Waldeyer's ring lesions and cervical adenopathy are common features, a knowledge of the symptoms and characteristics of MLEH is of considerable importance to the otolaryngologist. This report contributes four cases of MLEH to the 64 previously reported in the world literature. Of the four patients, three had Waldeyer's ring involvement and all had cervical lymphadenopathy. Table 1 summarizes the clinical data for these four patients; the details of one case are presented. TABLE 1. CASE No. 1. Age 2. Sex 3. Lymphadenopathy Cervical General 4. Waldeyer's ring 5. Splenomegaly 6. Hepatomegaly 7. Bone marrow 8. Skin involvement 9. B symptoms* 10. Treatment
11. Survival data 12. Cause of death
CASE REPORT In August 1977 a 70 year old Caucasian female was hospitalized following three and one-half years of painful upper extremity paresthesias, fatigue, and frequent cough; she had no history of weight loss or allergy. Other than treatment for anemia, the past history was noncontributory. The only significant physical findings were a small lymph node in the left posterior cervical triangle and a small, freely mobile, nontender node in the left axilla. There were no skin lesions or muscle wasting; the spleen and liver were not palpable. The patient had a mild normocytic normochromic anemia (hemoglobin 10.6, hematocrit 32.1 per cent) with normal indicies and red blood cell mass. The leucocyte count was 3200 with a normal differential count. The SMA-18 was normal with the exception of a mildly elevated LDH level (230 U.). The etiology of her symptoms remained unexplained after neurologic and hematologic work-ups; investigation for occult carcinoma and multiple myeloma was pursued. Bronchoscopy and bone marrow biopsy examinations were negative. A comprehensive immunologic survey revealed a slightly elevated serum protein electrophoresis pattern in the alpha one and two zones, latex fixation of 1:320, positive sheep cell agglutination (1:160), markedly depressed C4 (10 mcg. per ml.), a positive Raji cell test, and a cryoglobulin level of 1 per cent. Radiologic and nuclear medicine investigations were within normal limits. The patient returned to the hospital six weeks
Clinical and Treatment Data
1
2
3
4
78 F
79 F
52 F
42 M
+
+
+
+
--
+
+
+
+
--
+
+
--
+
+
+
--
+
--
+
--
+
--
+
Radiation: 4000 rads Steroids
Chemotherapy (single agent) Steroids
Steroids alone
10 mo. Myocardial infarction
5 mo. Sepsis (on chemotherapy)
Alive at 5 years Alive
Radiation: 4000 rads Chemotherapy (COPP) 14 mo. Sepsis (on chemotherapy)
*Unexplained fever, night sweats, weight loss.
230
MALIGNANT LYMPHOMA
Volume 1 Number 3 May 1980
later appearing pale and weak. She had a sore throat, dysphagia, hoarseness, and a two week weight loss of 11 pounds. Two lymph nodes were palpable in the left anterior cervical triangle, each 2 cm. in diameter; each posterior cervical triangle contained a node 1 cm. in diameter. All were freely mobile except for a node 2.5 cm. in diameter in the right anterior cervical triangle. Intraoral and endoscopic examination revealed an extensive ulcerative indurated lesion involving the left soft palate, uvula, tonsil, base of the tongue, vallecula, and epiglottis (Fig. 1). Ulcerations and edema were apparent in the larynx (Fig. 2); both pyriform sinuses were free of disease, as were the posterior pharyngeal wall
Figure 2. The larynx at direct laryngoscopy, demonstrating an ulcerative lesion involving the posterior right true vocal cord. The right arytenoid and posterior commissure are also affected by the disease.
Figure 1. Ulcerative lesions of malignant lymphoma with a high content of epithelioid histiocytes involving the left uvula, soft palate, and tonsil (arrows}.
LAUREN D. HOLINGER ET AL.
and nasopharynx. Biopsy specimens of the oropharynx, larynx, and right cervical lymph noa~e were interpreted as showing evidence of Lennews lymphoma (Figs. 3, 4). The results with subsequent staging procedures, including bone marrow biopsy, computerized axial tomographic scan, radionuclide scan, and x-ray examination were negative. Repeat laboratory study results were unchanged. Treatment was instituted: cobalt ~°, 4000 rads in five weeks, was administered to the larynx, oropharynx, and neck. After one week of radiation the lymph nodes had begun to regress; after two and one-half weeks they were no longer palpable. The patient's course was complicated by Pseudomonas pharyngitis and Klebsiella pneumonia. Complications of respiratory distress secondary to laryngeal edema and aspiration were managed with short term intubation, dexamethasone, and gastrostomy. At the completion of treatment there was no palpable cervical lymphadenopathy nor were there any remaining lesions in the pharynx or larynx. The patient was discharged on dexamethasone therapy, ambulatory 25 days after admission. The feeding gastrostomy was maintained. She failed to return for follow-up and during the next three months her health deteriorated. The patient expired in February 1978 from an apparent myocardial infarction; postmortem studies were not permitted.
231
American Journal of
Otolaryngology
Figure 3. Representative histologic section from the oropharyngeal biopsy specimen. The epithelial surface (upper right) has been replaced by a necrotic zone; beneath this is a diffuse polymorphous infiltrate composed of small and large lymphocytes, epithelioid histiocytes, and atypical "histiocyfic" cells with a polyploid nuclear configuration (hyperchromatic cells in lower center and right). Note the somewhat prominent vascular spaces. (Hemotoxylin and eosin stain, x 150.)
DISCUSSION The disease originally described by Lennert and Mestdagh 2 is now thought to represent a heterogenous disorder with similar but apparently distinct histologic and clinical features. 6 The disorder (Lennert's lymphoma) appears to be composed of (1) a variant of Hodgkin's disease without Dorothy ReedSternberg cells, 2 (2) immunoblastic lymphadenopathy 7 (angioimmunoblastic lymphadenopathy, s lymphogranulomatosis-X9), and (3) MLEH'. 6 (lymphoepithelioid cellular lymphoma, 1° non-Hodgkin's l y m p h o m a - m i x e d lymphocytic-"histiocytic""). MLEH is a clinicopathologic entity occurring in adults in the fifth and sixth decades. It is characterized by lymphadenopathy (especially cervical) and variable involvement of Waldeyer's ring, bone marrow, liver, and spleen. An allergic history and polyclonal hyperglobulinemia are common." 6 The histopathologic fea-
232
tures of MLEH include a diffuse polymorphous infiltrate with numerous epithelioid histiocytes and varying numbers of immnnoblasts. The anatomic distribution in the spleen, histologic similarities to a non-Hodgkin lymphoma described by Waldron et al., '2 and cell marker studies suggest that this is a disorder of the T cell arm of the immune system; 3, ,3 the polyclonal hyperglobulinemia noted occasionally may represent a B cell "host" response. The clinical course and response to therapy are unpredictable; death has frequently resulted from sepsis or diffuse lymphomatous involvement. Because of the varied clinical course and the polymorphous histologic features there remains uncertainty as to the exact nature, malignant potential, and relationship to other nonHodgkin lymphomas; the current consensus is that MLEH represents a malignant lymphoma.1, 6, 11
The optimal therapy for MLEH has not been well defined, although the disease has been
MALIGNANT LYMPHOMA
treated in many ways. 1, 4, 14 The 15 patients presented by Burke and Butler 1 treated at M.D. Anderson Hospital were managed as if they had stage I and II Hodgkin's disease, with radiation as the primary mode of therapy. More advanced disease was treated with chemotherapy either alone or in combination with radiotherapy; combination chemotherapy usually consisted of nitrogen mustard, oncovin, procarbazine, and prednisone. The authors observed that the patients tended to fall into two groups: one group showed only a partial response to any therapy and had a rapidly fatal course; the other group of patients had a more complete response and a longer survival. Kim et al. 6 discussed 19 patients managed according to a similar philosophy for early stages of MLEH with varied chemotherapeutic agents for advanced stages. They reported a poor response to all modalities: only 25 per cent had a complete response and those were of short median duration. Several patients treated with corticosteroid therapy without any cytotoxic agents
attained partial responses. Similarly, Staples and Getaz 14 described a case of MLEH involving the spleen and liver without lymphadenopathy in which the patient responded well to splenectomy. Among the four cases described in this report, therapy varied considerably. Patient 1 (case report), who presented with pharyngeal disease and cervical lymphadenopathy, was treated by irradiation and had a complete initial response. The second and third patients were initially treated with prednisone; the second patient had no response to corticosteroids or subsequent single chemotherapeutic agents and had a rapidly fatal course. The third patient, however, responded and is alive and well taking only corticosteroids. The fourth patient was treated with irradiation, nitrogen mustard, oncovin, procarbazine, and prednisone and other combinations of chemotherapy and had only a partial response. Our own experience and that of others demonstrate the unpredictable and variable course of
Volume 1 Number 3 May 1980
Figure 4. Section from the cervical lymph node, demonstrating the region of the paracortical zone. The node was diffusely replaced by a polymorphous infiltrate with numerous epithelioid histiocytes, lymphocytes, and infrequent immunoblasts (right of center) with prominent nucleoli. (Hematoxylin and eosin stain, x400.)
LAUREN D. HOLINGER ET AL.
233
American Journal of Otolaryngology
MLEH as well as the inconsistent nature of the response to various therapeutic modalities. Especially interesting are the dramatic response and continued remission of one patient (patient 3) taking corticosteroids alone, in contrast to others who follow a rapid downhill course to death in spite of (or as a complication of) chemotherapy.
3.
4. 5. 6.
CONCLUSION The otolaryngologist must consider MLEH in the differential diagnosis in older patients with cervical adenopathy and ulcerative lesions of Waldeyer's ring. Adequate tissue should be obtained for biopsy and the pathologist should be alerted to the possibility of MLEH; a clinical description of the areas involved should be included in the report sent with the biopsy specimens to the pathologist. Considerably more information regarding the clinical course of MLEH as well as information regarding the immunologic features, etiology, and response to therapy is necessary to define precisely the nature of the disorder.
7. 8. 9. 10. 11. 12.
13.
References 1. Burke, J. S., and Butler, J. J.: Malignant lymphoma with a high content of epithelioid histiocytes (Lennert's lymphoma). Am. J. Clin. Path., 66:1-9, 1976. 2. Lennert, K., and Mestdagh, J.: Lymphogranulomatosen
234
14.
mit konstant hohem Epitheliodzellgehalt. Vir. Arch. Abt. A Path. Anat., 344:1-20, 1968. Klein, M. A., Jaffe, M. B., and Neiman, R. S.: "Lennert's lymphoma" with transformation to malignant lymphoma, histiocytic type (immunoblastic sarcoma). Am. J. Clin. Path., 68:601-605, 1977. Robb-Smith, A. H. T.: Lennert lymphoma (letter). Lancet, 2:970, 1976. Staples, W. G., and Getaz, E. P.: Lympho-epithelioid cellular lymphoma (Lennert's lymphoma), a case report. S. Aft. Med. J., 52:555-556, 1977. Kim, H., Jacobs, C., Warnke, R. A., and Dorfman, R. F.: Malignant lymphoma with a high content of epithelioid lymphocytes, a distinct clinicopathologic entity and a form of so-called "Lennert's lymphoma." Cancer, 41:620-635, 1978. Lukes, R. J., and Tindle, B. H.: Immunoblastic lymphadenopathy, a hyperimmune entity resembling Hodgkin's disease. New Eng. J. Med., 292:1-8, 1975. Frizzera, G., Moran, E. M., and Rappaport, H.: Angioimmunoblastic lymphadenopathy with dysproteinemia. Lancet, 1:1070-1073, 1974. Radaszkiewicz, T., and Lennert, K.: Lymphogranulomatosis X. Dtsch. Med. Wochenschr., 100:1157-1163, 1975. Lennert, K., Mohri, N., Stein, H., and Kaiserling, E.: The histiopathology of malignant lymphomas. Br. J. Haematol., 31(Suppl.):193-203, 1975. Mann, R. B., Jaffe, E. S., and Berard, C. W.: Malignant l y m p h o m a s - - a conceptual understanding of morphologic diversity. Am. J. Pathol., 94:105-192, 1979. Waldron, J. A., et al.: Malignant lymphoma of peripheral T-lymphocyte origin. Immunologic, pathologic and clinical features in six patients. Cancer, 40:1604-1617, 1977. Palutke, M., et al.: Lennert's lymphoma, a T-cell neoplasm (letter), Am. J. Clin. Path., 69:643-646, 1978. Staples, W. G., and Getaz, E. P.: Prolonged survival in lymphoma with epithelioid hisUocytes (letter). S. Afr. Med. J., 52:833, 1977. 700 N. Michigan Avenue Chicago, Illinois 60011 (Dr. Holinger)
MALIGNANT LYMPHOMA
sinus. Trans. Am. Acad. Ophthalmol. Otolaryngol., 80:434-437, 1975. 16. Wyllie, J. W., III, Kern, E. B., and Djalilian, M.: Isolated sphenoid sinus lesions. Laryngoscope, 83:1252-1265, 1973.
Volume 1 Number 3 May 1980
Department of Otolaryngology, 727A University of California School of Medicine San Francisco, California 04143 (Dr. Ross)
The Otolaryngologic Manifestations of Malignant Lymphoma with a High Content of Epithelioid Histiocytes (Lennert's Lymphoma) LAUREN D. HOLINGER, M.D.,*
STEVEN F. SOLTES, M.D.,t PELLETTIERE, II, M.D.,~
EDMUND V,
DINO S. DELICATA, M.D.,§ AND ANANTHA I(. MURTHY, M.D.]I
Malignant lymphoma with a high content of epithelioid histiocytes is a rare nonHodgkin lymphoma first described by Lennert and Mestdagh (Lennert's lymphoma) in 1968. Distinguishing characteristics include frequent involvement of the nasopharynx, Waldeyer's ring, and cervical lymph nodes. Of the four patients included in this report, three had Waldeyer's ring involvement and four had cervical lymphadenopathy. Our experience and that of others demonstrate the unpredictable and variable course of the disease, as well as the inconsistent response to various therapeutic modalities; especially interesting is the remission obtained in one patient treated with corticosteroids alone, in contrast to the others who followed a rapid downhill course to death in spite of (or as a complication of) chemotherapy and radiation. The role of the otolaryngologist in the diagnosis and management of the disease is emphasized.
Accepted for publication December 12, 1979. *Assistant Professor, Department of Otolaryngology and Bronchoesophagology, Rush Medical College. Assistant Attending Physician, Rush-Presbyterian-St. Luke's Medical Center. Active Attending Physician, Children's Memorial Hospital. Clinical Staff, University of Illinois Eye and Ear Infirmary, Chicago, Illinois. tClinical Instructor, Department of Otolaryngology and Bronchoesophagology, University of Illinois Eye and Ear Infirmary, Chicago, Illinois. ¢Assistant Professor, Department of Pathology, Rush Medical College. Associate Attending Physician, Rush-PresbyterianSt. Luke's Medical Center, Chicago, Illinois. §Instructor, Department of Otolaryngology and Bronchoesophagalogy, Rush Medical College. Clinical Staff, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois. 1~4ssistant Professor, Department of Therapeutic Radiology, Rush Medical College. Clinical Staff, Rush-Presbyterian-St. Luke's Medical Center and Swedish Covenant Hospital, Chicago, Illinois. American Journal of Otalaryngology --Volume 1, Number 3, May 1980
229
American Journal of
Otolaryngology
Malignant lymphoma with a high content of epithelioid histiocytes (MLEH) is a non-Hodgkin lymphoma' first described by Lennert and Mestdagh (Lennert's lymphoma) in 1968. 2 Although this relatively recently described and rare disease has been documented in the literature of several disciplines, 3-~to date there have been no reports in the otolaryngologic and head and neck literature, despite the fact that distinguishing features include a high frequency of involvement of the nasopharynx, Waldeyer's ring, and cervical lymph nodes. MLEH is most commonly seen in the middle aged or elderly, and the symptoms of lymphadenopathy, hepatomegaly, and splenomegaly are relatively frequent. 2,s" 7 The entity produces a distinctive histologic pattern characterized by a high number of epithelioid cells and an absence of Dorothy Reed-Sternberg cells. 2 Lennert's original 30 cases illustrated the frequent tonsillar involvement (five of 30).2 Burke and Butler' presented 15 cases in which they described a predilection for Waldeyer's ring involvement (three of 15). Since Waldeyer's ring lesions and cervical adenopathy are common features, a knowledge of the symptoms and characteristics of MLEH is of considerable importance to the otolaryngologist. This report contributes four cases of MLEH to the 64 previously reported in the world literature. Of the four patients, three had Waldeyer's ring involvement and all had cervical lymphadenopathy. Table 1 summarizes the clinical data for these four patients; the details of one case are presented. TABLE 1. CASE No. 1. Age 2. Sex 3. Lymphadenopathy Cervical General 4. Waldeyer's ring 5. Splenomegaly 6. Hepatomegaly 7. Bone marrow 8. Skin involvement 9. B symptoms* 10. Treatment
11. Survival data 12. Cause of death
CASE REPORT In August 1977 a 70 year old Caucasian female was hospitalized following three and one-half years of painful upper extremity paresthesias, fatigue, and frequent cough; she had no history of weight loss or allergy. Other than treatment for anemia, the past history was noncontributory. The only significant physical findings were a small lymph node in the left posterior cervical triangle and a small, freely mobile, nontender node in the left axilla. There were no skin lesions or muscle wasting; the spleen and liver were not palpable. The patient had a mild normocytic normochromic anemia (hemoglobin 10.6, hematocrit 32.1 per cent) with normal indicies and red blood cell mass. The leucocyte count was 3200 with a normal differential count. The SMA-18 was normal with the exception of a mildly elevated LDH level (230 U.). The etiology of her symptoms remained unexplained after neurologic and hematologic work-ups; investigation for occult carcinoma and multiple myeloma was pursued. Bronchoscopy and bone marrow biopsy examinations were negative. A comprehensive immunologic survey revealed a slightly elevated serum protein electrophoresis pattern in the alpha one and two zones, latex fixation of 1:320, positive sheep cell agglutination (1:160), markedly depressed C4 (10 mcg. per ml.), a positive Raji cell test, and a cryoglobulin level of 1 per cent. Radiologic and nuclear medicine investigations were within normal limits. The patient returned to the hospital six weeks
Clinical and Treatment Data
1
2
3
4
78 F
79 F
52 F
42 M
+
+
+
+
--
+
+
+
+
--
+
+
--
+
+
+
--
+
--
+
--
+
--
+
Radiation: 4000 rads Steroids
Chemotherapy (single agent) Steroids
Steroids alone
10 mo. Myocardial infarction
5 mo. Sepsis (on chemotherapy)
Alive at 5 years Alive
Radiation: 4000 rads Chemotherapy (COPP) 14 mo. Sepsis (on chemotherapy)
*Unexplained fever, night sweats, weight loss.
230
MALIGNANT LYMPHOMA
Volume 1 Number 3 May 1980
later appearing pale and weak. She had a sore throat, dysphagia, hoarseness, and a two week weight loss of 11 pounds. Two lymph nodes were palpable in the left anterior cervical triangle, each 2 cm. in diameter; each posterior cervical triangle contained a node 1 cm. in diameter. All were freely mobile except for a node 2.5 cm. in diameter in the right anterior cervical triangle. Intraoral and endoscopic examination revealed an extensive ulcerative indurated lesion involving the left soft palate, uvula, tonsil, base of the tongue, vallecula, and epiglottis (Fig. 1). Ulcerations and edema were apparent in the larynx (Fig. 2); both pyriform sinuses were free of disease, as were the posterior pharyngeal wall
Figure 2. The larynx at direct laryngoscopy, demonstrating an ulcerative lesion involving the posterior right true vocal cord. The right arytenoid and posterior commissure are also affected by the disease.
Figure 1. Ulcerative lesions of malignant lymphoma with a high content of epithelioid histiocytes involving the left uvula, soft palate, and tonsil (arrows}.
LAUREN D. HOLINGER ET AL.
and nasopharynx. Biopsy specimens of the oropharynx, larynx, and right cervical lymph noa~e were interpreted as showing evidence of Lennews lymphoma (Figs. 3, 4). The results with subsequent staging procedures, including bone marrow biopsy, computerized axial tomographic scan, radionuclide scan, and x-ray examination were negative. Repeat laboratory study results were unchanged. Treatment was instituted: cobalt ~°, 4000 rads in five weeks, was administered to the larynx, oropharynx, and neck. After one week of radiation the lymph nodes had begun to regress; after two and one-half weeks they were no longer palpable. The patient's course was complicated by Pseudomonas pharyngitis and Klebsiella pneumonia. Complications of respiratory distress secondary to laryngeal edema and aspiration were managed with short term intubation, dexamethasone, and gastrostomy. At the completion of treatment there was no palpable cervical lymphadenopathy nor were there any remaining lesions in the pharynx or larynx. The patient was discharged on dexamethasone therapy, ambulatory 25 days after admission. The feeding gastrostomy was maintained. She failed to return for follow-up and during the next three months her health deteriorated. The patient expired in February 1978 from an apparent myocardial infarction; postmortem studies were not permitted.
231
American Journal of
Otolaryngology
Figure 3. Representative histologic section from the oropharyngeal biopsy specimen. The epithelial surface (upper right) has been replaced by a necrotic zone; beneath this is a diffuse polymorphous infiltrate composed of small and large lymphocytes, epithelioid histiocytes, and atypical "histiocyfic" cells with a polyploid nuclear configuration (hyperchromatic cells in lower center and right). Note the somewhat prominent vascular spaces. (Hemotoxylin and eosin stain, x 150.)
DISCUSSION The disease originally described by Lennert and Mestdagh 2 is now thought to represent a heterogenous disorder with similar but apparently distinct histologic and clinical features. 6 The disorder (Lennert's lymphoma) appears to be composed of (1) a variant of Hodgkin's disease without Dorothy ReedSternberg cells, 2 (2) immunoblastic lymphadenopathy 7 (angioimmunoblastic lymphadenopathy, s lymphogranulomatosis-X9), and (3) MLEH'. 6 (lymphoepithelioid cellular lymphoma, 1° non-Hodgkin's l y m p h o m a - m i x e d lymphocytic-"histiocytic""). MLEH is a clinicopathologic entity occurring in adults in the fifth and sixth decades. It is characterized by lymphadenopathy (especially cervical) and variable involvement of Waldeyer's ring, bone marrow, liver, and spleen. An allergic history and polyclonal hyperglobulinemia are common." 6 The histopathologic fea-
232
tures of MLEH include a diffuse polymorphous infiltrate with numerous epithelioid histiocytes and varying numbers of immnnoblasts. The anatomic distribution in the spleen, histologic similarities to a non-Hodgkin lymphoma described by Waldron et al., '2 and cell marker studies suggest that this is a disorder of the T cell arm of the immune system; 3, ,3 the polyclonal hyperglobulinemia noted occasionally may represent a B cell "host" response. The clinical course and response to therapy are unpredictable; death has frequently resulted from sepsis or diffuse lymphomatous involvement. Because of the varied clinical course and the polymorphous histologic features there remains uncertainty as to the exact nature, malignant potential, and relationship to other nonHodgkin lymphomas; the current consensus is that MLEH represents a malignant lymphoma.1, 6, 11
The optimal therapy for MLEH has not been well defined, although the disease has been
MALIGNANT LYMPHOMA
treated in many ways. 1, 4, 14 The 15 patients presented by Burke and Butler 1 treated at M.D. Anderson Hospital were managed as if they had stage I and II Hodgkin's disease, with radiation as the primary mode of therapy. More advanced disease was treated with chemotherapy either alone or in combination with radiotherapy; combination chemotherapy usually consisted of nitrogen mustard, oncovin, procarbazine, and prednisone. The authors observed that the patients tended to fall into two groups: one group showed only a partial response to any therapy and had a rapidly fatal course; the other group of patients had a more complete response and a longer survival. Kim et al. 6 discussed 19 patients managed according to a similar philosophy for early stages of MLEH with varied chemotherapeutic agents for advanced stages. They reported a poor response to all modalities: only 25 per cent had a complete response and those were of short median duration. Several patients treated with corticosteroid therapy without any cytotoxic agents
attained partial responses. Similarly, Staples and Getaz 14 described a case of MLEH involving the spleen and liver without lymphadenopathy in which the patient responded well to splenectomy. Among the four cases described in this report, therapy varied considerably. Patient 1 (case report), who presented with pharyngeal disease and cervical lymphadenopathy, was treated by irradiation and had a complete initial response. The second and third patients were initially treated with prednisone; the second patient had no response to corticosteroids or subsequent single chemotherapeutic agents and had a rapidly fatal course. The third patient, however, responded and is alive and well taking only corticosteroids. The fourth patient was treated with irradiation, nitrogen mustard, oncovin, procarbazine, and prednisone and other combinations of chemotherapy and had only a partial response. Our own experience and that of others demonstrate the unpredictable and variable course of
Volume 1 Number 3 May 1980
Figure 4. Section from the cervical lymph node, demonstrating the region of the paracortical zone. The node was diffusely replaced by a polymorphous infiltrate with numerous epithelioid histiocytes, lymphocytes, and infrequent immunoblasts (right of center) with prominent nucleoli. (Hematoxylin and eosin stain, x400.)
LAUREN D. HOLINGER ET AL.
233
American Journal of Otolaryngology
MLEH as well as the inconsistent nature of the response to various therapeutic modalities. Especially interesting are the dramatic response and continued remission of one patient (patient 3) taking corticosteroids alone, in contrast to others who follow a rapid downhill course to death in spite of (or as a complication of) chemotherapy.
3.
4. 5. 6.
CONCLUSION The otolaryngologist must consider MLEH in the differential diagnosis in older patients with cervical adenopathy and ulcerative lesions of Waldeyer's ring. Adequate tissue should be obtained for biopsy and the pathologist should be alerted to the possibility of MLEH; a clinical description of the areas involved should be included in the report sent with the biopsy specimens to the pathologist. Considerably more information regarding the clinical course of MLEH as well as information regarding the immunologic features, etiology, and response to therapy is necessary to define precisely the nature of the disorder.
7. 8. 9. 10. 11. 12.
13.
References 1. Burke, J. S., and Butler, J. J.: Malignant lymphoma with a high content of epithelioid histiocytes (Lennert's lymphoma). Am. J. Clin. Path., 66:1-9, 1976. 2. Lennert, K., and Mestdagh, J.: Lymphogranulomatosen
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14.
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