The Journal of Laryngology and Otology April 1979. Vol. 93. pp. 417-422
Primary lymphoma of the parotid gland By L. PODOSHIN, Y. TALMON, A. GRISHKAN and M. FRADIS (Haifa, Israel) Introduction SALIVARY gland tumours are unique among head and neck neoplasms in the diverse pathology they manifest, variety of clinical behaviour and furthermore the rarity of some types. Primary malignant lymphoma of the salivary glands is very rare. It is difficult to arrive at any conclusions from examining the literature as the number of cases is too small (aboutfifty)and documentation is not always satisfactory. Surgeons normally do not expect to find primary lymphoma in the salivary glands and pathologists find it difficult to report a conclusive diagnosis based on frozen section only. This uncertainty could result in the performance of an unnecessarily radical operation. Two patients with primary non-Hodgkin's malignant lymphoma of the parotid gland are reported. The classification used follows Rappaport's (1966) system. Case 1.
A 74-year-old woman presented in the out-patient clinic with a firm painless mass in the right parotid gland of two-weeks' duration. There was no history of upper respiratory or dental infection. A 10-day course of antibiotics was given without effect. Cytologic examination of material taken byfineneedle aspiration revealed malignant cells, but further analysis was impossible. The patient was admitted to the hospital. On physical examination the patient had a firm, non-tender mass in the right parotid gland, 3 x 3 cm in size. A partial parotidectomy was performed. The tumour was found to lie deep to the facial nerve. On macroscopic examination, the tumour was a grey, soft mass within the parotid gland; on microscopic examination, there was diffuse infiltration of the parenchyma by immature lymphocytes. Tumour cells were mainly around the acini and between ducts. Final diagnosis: Malignant lymphoma, diffuse, poorly differentiated lymphocytic type (Figs. 1, 2, 3 and 4). The post-operative course was uneventful. Further investigations, including I.V.P., radio-isotope scanning of liver and spleen and biopsies of nasopharynx, bone marrow and bone revealed no signs of the disease. The patient was treated with 6,000 R of cobalt irradiation and for one year no recurrence has been noted. Case 2.
An 80-year-old woman presented with one-year history of painless right parotid swelling. Physical examination revealed a soft mass, 2 x 3 cm, in the right parotid gland. E.N.T. examination was otherwise normal. Cytologic examination of repeatedfineneedle aspirations revealed normal lymphocytes and a few highly atypical cells. The patient refused further investigation. Three months later she 417
418
L. PODOSHIN, Y. TALMON, A. GRISHKAN AND M. FRADIS
FIG. 1 Diffuse infiltration of poorly differentiated lymphocytes in the parenchyma of the parotid gland, between the acini and the ducts (H. & E. x 32).
...
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V.-:
V 4 FIG. 2 Same as Fig. 1 in greater magnification (H. & E. x 320).
CLINICAL RECORDS
419
FIG. 3 Invasion of atypical lymphocytes around a duct (H. & E. x 32).
FIG. 4 Poorly differentiated lymphocytes of various shapes and sizes, invading the parotid gland (H. & E. x 800). ^^
420
L. PODOSHIN, Y. TALMON, A. GRISHKAN AND M. FRADIS
returned, this time complaining of further swelling and pain in the right cheek. On examination, a red tender mass was found in the right parotid gland, measuring 4 x 4 cm, with infiltration of the skin. This time the patient was admitted to the hospital. Physical examination, with the exception of the previously described parotid mass, and laboratory data were within normal limits. At operation a parotid tumour was found overlying the facial nerve and infiltrating the skin. Superficial parotidectomy was performed and the involved skin was excised. Split-thickness skin graft was used to close the skin defect. On macroscopic examination the tumour was seen as a white infiltration of the gland. On microscopic examination there was a diffuse infiltration of the parenchyma with immature lymphocytes and histiocytes. The tumour cells were seen between acini and ducts, some of which were obliterated (Figs. 5 and 6). The malignant cells invaded the fat tissue around the parotid gland and the skin. The post-operative course was uneventful. Further investigation revealed no signs of the disease elsewhere. The patient was treated with 6,000 R of cobalt irradiation and in follow-up of a few months' duration there was no recurrence. Discussion Primary malignant lymphoma of the salivary glands is extremely rare. Several large series of salivary gland tumours Molander and Pack, 1963; Freedman, 1971; Foote and Fragell, 1954; Woods et ah, 1975; Rosenberg et ah, 1961; Batsakis and Regezi, 1977) contain occasional reports of the disease. Mine et ah (1976), recently reviewing the literature, found only 43 possible cases of primary lymphoma of the salivary glands, of which 29 are incompletely documented.
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FIG. 5 Diffuse infiltration of poorly differentiated lymphocytes and histiocytes into the parenchyma of the parotid gland (H. & E. x 320).
CLINICAL RECORDS
421
FIG. 6 Same as Fig. 5, in greater magnification (H. & E. x800).
Almost all primary lymphomas of the salivary glands occur in the parotid gland (Batsakis and Regezi, 1977; Mine et al, 1976; Hyman and Wolff, 1976; Hatziotis and Asprides, 1964). A possible explanation is the presence of lymph nodes and lymphoid aggregates within the parotid gland which are absent in the other major salivary glands (Mine et al, 1976; Thompson and Bryant, 1950). In these instances the lymphoma originates from lymphatic tissue and therefore cannot be considered as extranodal. Hyman and Wolff in 1976, examining 30 cases of non-Hodgkin's salivary gland lymphomas, found the histiocytic type and nodular pattern to be more common than the others. These authors suggested that primary lymphoma of the salivary gland must fulfill the three following criteria: (1) no other extra-salivary lymphoma; (2) histologic proof that the lymphoma originated in the salivary parenchyma and did not invade it from adjacent lymph nodes; (3) architectural and cytologic confirmation of the malignant nature of the lympho-reticular infiltrate. The cases represented by us fulfil these criteria. The prognosis of primary lymphoma of the salivary glands seems to be relatively good (Batsakis and Regezi, 1977; Mine et al, 1976; Saltzstein, 1969); but available data do not permit adequate analysis. Salivary lymphoma associated with Sjogren's syndrome has a less promising prognosis (Batsakis and Regezi, 1977; Anderson and Talal, 1971); such a combination is not unusual as the association of lympho-proliferative disorders with Sjogren's syndrome is well known (Batsakis and Regezi, 1977; Anderson and Talal, 1971; Deegan, 1977; Miller, 1976). When operating upon the salivary gland, the surgeon often must await the report on permanent sections to know the histologic nature of the tumour excised. The diagnostic pre-operative methods of sialography, scanning, fine needle
422
L. PODOSHIN, Y. TALMON, A. GRISHKAN AND M. FRADIS
aspiration and frozen sections are sometimes not reliable in a specific case. If there is a possibility of salivary gland lymphoma the surgeon should perform a biopsy and await the result of definitive histology before deciding on further treatment. Thus, if the histology reveals a lymphoma an unnecessary radical procedure will have been avoided. This is a very rare tumour and clearly additional reports and follow-up data are needed if its behaviour is to be more fully appreciated. Summary
Primary lymphomas of the salivary glands are very rare. Approximately fifty possible cases have been reported. Whether primary malignant lymphoma of the parotid gland is extranodular or not, is not yet clear. We describe two cases of primary lymphoma of the parotid gland and review the literature of this condition. REFERENCES ANDERSON, L. G., and TALAL, N. (1971) Clinical Experimental Immunology, 9, 199. BATSAKIS, J. G., and REGEZI, J. A. (1977) The Otolaryngology Clinics of North America, 10, 309. DEEGAN, M. J. (1977) Otolaryngologic Clinics of North America, 10, 351. FOOTE, F. W., and FRAGELL, E. L. (1954) Tumours of the major salivary glands, in Atlas of Tumour Pathology, section IV, fasc. 2. Washington DC, Armed Forces Institute of Pathology. FREEDMAN, S. J. (1971) Archives of Otolaryngology, 93, 123. HATZIOTIS, J., and ASPRIDES, C. (1964) Oral Surgery, 17, 503. HYMAN, G. A., and WOLFF, M. (1976) American Journal of Clinical Pathology, 65, 421. MILLER, D. G. (1976) Annals of Internal Medicine, 66, 507. MINE, F. A., COOPER, H. S., and EGGLESTON, J. C. (1976) Cancer, 37, 906.
MOLANDER, D. W., and PACK, G. T. (1963) Review of Surgery, 20, 3. RAPPAPORT, H. (1966) Tumours of the Haematopoietic System, in Atlas of Human Pathology, section III, fasc. 8. Washington DC. Armed Forces Institute of Pathology. ROSENBERG, S. A., DIAMOND, H. D., JASLOWITZ, B., and CRAER, F. F. (1961) Medicine, 41, 31.
SALTZSTEIN, S. L. (1969) Annals of Pathology, 159. THOMPSON, A. S., and BRYANT, H. C. (1950) American Journal of Pathology, 26, 807. WOODS, J. E., CHONG, Q. C , and BEAHRS, O. H. (1975) American Journal of Surgery, 130,460. Departments of Otolaryngology and Pathology, Rothschild University Hospital, Aba Khoushi School of Medicine, Haifa, Israel.
Primary lymphoma of the parotid gland By L. PODOSHIN, Y. TALMON, A. GRISHKAN and M. FRADIS (Haifa, Israel) Introduction SALIVARY gland tumours are unique among head and neck neoplasms in the diverse pathology they manifest, variety of clinical behaviour and furthermore the rarity of some types. Primary malignant lymphoma of the salivary glands is very rare. It is difficult to arrive at any conclusions from examining the literature as the number of cases is too small (aboutfifty)and documentation is not always satisfactory. Surgeons normally do not expect to find primary lymphoma in the salivary glands and pathologists find it difficult to report a conclusive diagnosis based on frozen section only. This uncertainty could result in the performance of an unnecessarily radical operation. Two patients with primary non-Hodgkin's malignant lymphoma of the parotid gland are reported. The classification used follows Rappaport's (1966) system. Case 1.
A 74-year-old woman presented in the out-patient clinic with a firm painless mass in the right parotid gland of two-weeks' duration. There was no history of upper respiratory or dental infection. A 10-day course of antibiotics was given without effect. Cytologic examination of material taken byfineneedle aspiration revealed malignant cells, but further analysis was impossible. The patient was admitted to the hospital. On physical examination the patient had a firm, non-tender mass in the right parotid gland, 3 x 3 cm in size. A partial parotidectomy was performed. The tumour was found to lie deep to the facial nerve. On macroscopic examination, the tumour was a grey, soft mass within the parotid gland; on microscopic examination, there was diffuse infiltration of the parenchyma by immature lymphocytes. Tumour cells were mainly around the acini and between ducts. Final diagnosis: Malignant lymphoma, diffuse, poorly differentiated lymphocytic type (Figs. 1, 2, 3 and 4). The post-operative course was uneventful. Further investigations, including I.V.P., radio-isotope scanning of liver and spleen and biopsies of nasopharynx, bone marrow and bone revealed no signs of the disease. The patient was treated with 6,000 R of cobalt irradiation and for one year no recurrence has been noted. Case 2.
An 80-year-old woman presented with one-year history of painless right parotid swelling. Physical examination revealed a soft mass, 2 x 3 cm, in the right parotid gland. E.N.T. examination was otherwise normal. Cytologic examination of repeatedfineneedle aspirations revealed normal lymphocytes and a few highly atypical cells. The patient refused further investigation. Three months later she 417
418
L. PODOSHIN, Y. TALMON, A. GRISHKAN AND M. FRADIS
FIG. 1 Diffuse infiltration of poorly differentiated lymphocytes in the parenchyma of the parotid gland, between the acini and the ducts (H. & E. x 32).
...
>y.
.Ci.
V.-:
V 4 FIG. 2 Same as Fig. 1 in greater magnification (H. & E. x 320).
CLINICAL RECORDS
419
FIG. 3 Invasion of atypical lymphocytes around a duct (H. & E. x 32).
FIG. 4 Poorly differentiated lymphocytes of various shapes and sizes, invading the parotid gland (H. & E. x 800). ^^
420
L. PODOSHIN, Y. TALMON, A. GRISHKAN AND M. FRADIS
returned, this time complaining of further swelling and pain in the right cheek. On examination, a red tender mass was found in the right parotid gland, measuring 4 x 4 cm, with infiltration of the skin. This time the patient was admitted to the hospital. Physical examination, with the exception of the previously described parotid mass, and laboratory data were within normal limits. At operation a parotid tumour was found overlying the facial nerve and infiltrating the skin. Superficial parotidectomy was performed and the involved skin was excised. Split-thickness skin graft was used to close the skin defect. On macroscopic examination the tumour was seen as a white infiltration of the gland. On microscopic examination there was a diffuse infiltration of the parenchyma with immature lymphocytes and histiocytes. The tumour cells were seen between acini and ducts, some of which were obliterated (Figs. 5 and 6). The malignant cells invaded the fat tissue around the parotid gland and the skin. The post-operative course was uneventful. Further investigation revealed no signs of the disease elsewhere. The patient was treated with 6,000 R of cobalt irradiation and in follow-up of a few months' duration there was no recurrence. Discussion Primary malignant lymphoma of the salivary glands is extremely rare. Several large series of salivary gland tumours Molander and Pack, 1963; Freedman, 1971; Foote and Fragell, 1954; Woods et ah, 1975; Rosenberg et ah, 1961; Batsakis and Regezi, 1977) contain occasional reports of the disease. Mine et ah (1976), recently reviewing the literature, found only 43 possible cases of primary lymphoma of the salivary glands, of which 29 are incompletely documented.
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FIG. 5 Diffuse infiltration of poorly differentiated lymphocytes and histiocytes into the parenchyma of the parotid gland (H. & E. x 320).
CLINICAL RECORDS
421
FIG. 6 Same as Fig. 5, in greater magnification (H. & E. x800).
Almost all primary lymphomas of the salivary glands occur in the parotid gland (Batsakis and Regezi, 1977; Mine et al, 1976; Hyman and Wolff, 1976; Hatziotis and Asprides, 1964). A possible explanation is the presence of lymph nodes and lymphoid aggregates within the parotid gland which are absent in the other major salivary glands (Mine et al, 1976; Thompson and Bryant, 1950). In these instances the lymphoma originates from lymphatic tissue and therefore cannot be considered as extranodal. Hyman and Wolff in 1976, examining 30 cases of non-Hodgkin's salivary gland lymphomas, found the histiocytic type and nodular pattern to be more common than the others. These authors suggested that primary lymphoma of the salivary gland must fulfill the three following criteria: (1) no other extra-salivary lymphoma; (2) histologic proof that the lymphoma originated in the salivary parenchyma and did not invade it from adjacent lymph nodes; (3) architectural and cytologic confirmation of the malignant nature of the lympho-reticular infiltrate. The cases represented by us fulfil these criteria. The prognosis of primary lymphoma of the salivary glands seems to be relatively good (Batsakis and Regezi, 1977; Mine et al, 1976; Saltzstein, 1969); but available data do not permit adequate analysis. Salivary lymphoma associated with Sjogren's syndrome has a less promising prognosis (Batsakis and Regezi, 1977; Anderson and Talal, 1971); such a combination is not unusual as the association of lympho-proliferative disorders with Sjogren's syndrome is well known (Batsakis and Regezi, 1977; Anderson and Talal, 1971; Deegan, 1977; Miller, 1976). When operating upon the salivary gland, the surgeon often must await the report on permanent sections to know the histologic nature of the tumour excised. The diagnostic pre-operative methods of sialography, scanning, fine needle
422
L. PODOSHIN, Y. TALMON, A. GRISHKAN AND M. FRADIS
aspiration and frozen sections are sometimes not reliable in a specific case. If there is a possibility of salivary gland lymphoma the surgeon should perform a biopsy and await the result of definitive histology before deciding on further treatment. Thus, if the histology reveals a lymphoma an unnecessary radical procedure will have been avoided. This is a very rare tumour and clearly additional reports and follow-up data are needed if its behaviour is to be more fully appreciated. Summary
Primary lymphomas of the salivary glands are very rare. Approximately fifty possible cases have been reported. Whether primary malignant lymphoma of the parotid gland is extranodular or not, is not yet clear. We describe two cases of primary lymphoma of the parotid gland and review the literature of this condition. REFERENCES ANDERSON, L. G., and TALAL, N. (1971) Clinical Experimental Immunology, 9, 199. BATSAKIS, J. G., and REGEZI, J. A. (1977) The Otolaryngology Clinics of North America, 10, 309. DEEGAN, M. J. (1977) Otolaryngologic Clinics of North America, 10, 351. FOOTE, F. W., and FRAGELL, E. L. (1954) Tumours of the major salivary glands, in Atlas of Tumour Pathology, section IV, fasc. 2. Washington DC, Armed Forces Institute of Pathology. FREEDMAN, S. J. (1971) Archives of Otolaryngology, 93, 123. HATZIOTIS, J., and ASPRIDES, C. (1964) Oral Surgery, 17, 503. HYMAN, G. A., and WOLFF, M. (1976) American Journal of Clinical Pathology, 65, 421. MILLER, D. G. (1976) Annals of Internal Medicine, 66, 507. MINE, F. A., COOPER, H. S., and EGGLESTON, J. C. (1976) Cancer, 37, 906.
MOLANDER, D. W., and PACK, G. T. (1963) Review of Surgery, 20, 3. RAPPAPORT, H. (1966) Tumours of the Haematopoietic System, in Atlas of Human Pathology, section III, fasc. 8. Washington DC. Armed Forces Institute of Pathology. ROSENBERG, S. A., DIAMOND, H. D., JASLOWITZ, B., and CRAER, F. F. (1961) Medicine, 41, 31.
SALTZSTEIN, S. L. (1969) Annals of Pathology, 159. THOMPSON, A. S., and BRYANT, H. C. (1950) American Journal of Pathology, 26, 807. WOODS, J. E., CHONG, Q. C , and BEAHRS, O. H. (1975) American Journal of Surgery, 130,460. Departments of Otolaryngology and Pathology, Rothschild University Hospital, Aba Khoushi School of Medicine, Haifa, Israel.
