IgA ASSOCIATED LYMPHOPLASMACYTIC TUMOR INVOLVING T H E CONJUNCTIVA, EYELID, AND ORBIT LEE M. JAMPOL, M.D.,
J O H N C. MARSH, M.D., New Haven,
AND DANIEL M. ALBERT,
M.D.
Connecticut
AND LORENZ
E.
ZIMMERMAN,
Washington,
Lymphoid tumors of the orbit represent a challenging diagnostic problem for the ophthalmologist and pathologist. These tu mors include a wide spectrum of diseases from benign lesions (pseudotumors) to ob viously malignant lesions.1·2 According to Henderson,3 malignant lymphoreticular tu mors comprise about 11% of all orbital tumors. Malignant lymphomas (including those associated with Waldenström's macroglobulinemia4-6), multiple myeloma,7 and leukemias all may involve, and even present in, the orbit. We now report on a patient with an unusual conjunctival, eyelid, and orbital tumor associated with subcutaneous masses and lymph node involvement. Inter esting features in this case included (1) ex tensive amyloid deposition within the tumor, (2) a monoclonal IgA serum spike, with negative urinary Bence Jones proteins, (3) tumor cells that cytologically appeared to be intermediate between the lymphocyte and plasma cell, with prominent Dutcher bodies, and (4) an indolent clinical course. From the Department of Ophthalmology and Visual Science ( D r s . Jampol and.Albert), and the Departments of Medicine and Pharmacology (Dr. Marsh), Yale University School of Medicine, New Haven, Connecticut, and the Armed Forces Institute of Pathology, Ophthalmic Pathology Branch (Dr. Zimmerman), Washington, D.C. This work was supported in part by the Ida and Louis Katz Memorial Fund through a grant from Fight for Sight, Inc., New York, and by the Seeing Eye, Inc., Morristown, New Jersey. Dr. Marsh is a Faculty Research Associate, American Cancer Society. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. Reprint requests to Lee M. Jampol, M.D., Illi nois Eye and E a r Infirmary, 1855 W. Taylor St., Chicago, IL 60612.
M.D.
D.C. CASE REPORT
The patient, a 65-year-old white man, was in good health until February 1964, when he de veloped a 10-mm violaceous subconjunctival mass in the region of the right lateral rectus muscle. A biopsy specimen showed a lymphoid tumor. H e was treated with orbital irradiation, receiving 2,500 rads in 12 days with complete clinical re gression of the mass. He then remained well un til November 1967, when he noted the onset of masses in the left epigastric area, right inguinal area, and the right buttocks. A biopsy specimen from the abdominal wall showed lymphosarcoma with extensive amyloid and para-amyloid deposits. H e was treated with 3,500 rads in 18 days to the abdominal wall and buttocks and 3,000 rads in 17 days to the right inguinal lymph nodes. There was dramatic regression of the masses. In June 1969, he noted additional masses on his left back, left breast, and in the left axilla. A biopsy speci men was interpreted as malignant lymphoreticular neoplasm with amyloid deposition. H e was given 3,500 rads to the axilla over 21 days. At this time his hemogram was normal and his albumin/ globulin ratio was 4.6/4.1 g/100 ml, but protein electrophoresis was not done. X-ray films of the bones and chest were normal. In December 1969, he developed herpes zoster of the left axilla and left anterior chest. He was given 1,500 rads to the thoracic spine over the next 36 days for the pain, but since then he continues to have severe pain and hyperesthesia in the left axilla and anterior chest. In 1971, an inguinal hernia was repaired. At this time a calcified mass was observed on an x-ray film of the abdomen in the region of the right kidney. An intravenous pyelogram showed nonvisualization of the right kidney. Bone films showed degenerative arthritis of the spine and generalized osteoporosis, but no lytic lesions. A liver scan was normal. The patient was referred to this hospital in October 1972, with a one-year history of growth in the left upper eyelid. A 30 X 12-mm rubbery firm mass was observed in the left upper eyelid. The best corrected visual acuity was R.E. : 20/25, and L.E. : 20/30. The remainder of the ophthalmic examination including slit-lamp ex amination, ocular tensions, perimetry studies, and ophthalmoscopy was normal. Pertinent findings on general physical examination included two subcu taneous nodules of the chest and an enlarged right
279
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supraclavicular lymph node. There was no bony tenderness or organomegaly. The results of a hemogram, blood urea nitrogen, serum creatinine, liver function tests, serum calcium, and serum phosphorus were all normal. Serum uric acid was 7.9 mg/100 ml. Serum protein electrophoresis showed a spike between the beta- and gammaglobulin portions. Values for individual serum proteins were: albumin, 3.3 g/100 ml; alpha-1 globulin, 0.36 g/100 ml; alpha-2 globulin, 0.S8 g/100 ml; beta globulin, 1.31 g/100 ml; gamma globulin, 0.77 g/100 ml. Serum immunoelectrophoresis re vealed a monoclonal IgA component with kappa light chains. A diffuse elevation of IgM was also present and IgG was normal. Subsequent quanti tative immunoglobulin values were IgG, 1,320 mg/ 100 ml (normal 600-2,000) ; IgA, 1,300 mg/100 ml (normal 60-400) ; IgM, 775 mg/100 ml (normal 20-250). Heat and acetic acid tests of the urine for Bence Jones protein were negative on two occasions. Immunoelectrophoresis of concentrated urine revealed free kappa light chain proteins. The amount was low, however, being less than 100 mg/liter. This value is probably within the normal range.8 The serum viscosity was normal. Serum cold agglutinins and cryoglobulins were negative. The bone marrow was of normal cellularity with a myeloid to an erythroid ratio of 2.3:1 (a normal value). There were 9% lymphocytes and 1% plasma cells, both of normal appearance. Chest and bone x-ray films were unremarkable. A renal arteriogram to evaluate the nonfunctioning right kidney showed an avascular mass consistent with an old perirenal abscess. Under local anesthesia, an excisional biopsy of the left eyelid lesion was attempted but the lesion extended through the orbital septum into the orbit and thus was only partially resected. Subsequently, this area was treated with 2,000 rads over seven days. The patient was last seen March 21, 1974, with no recurrence of the previously treated tumor masses. A biopsy of the enlarged right supraclavicular node showed orly necrotic tissue and planned tissue culture and. immunofluorescent studies of this specimen were not possible. The findings on repeated serum protein electrophoresis have remained unchanged.
FEBRUARY, 1975
ation between the cells in different areas of the tumor but the predominant cell type ap peared to be a plasmacytoid lymphocyte. T h e tumor contained a fibrovascular matrix and scattered reticulum cells. A prominent fea ture of the tumor was the presence of homogeneous eosinophilic material deposited around and within the walls of blood vessels. Stains of these areas with cresyl violet and Congo red for amyloid were positive (Fig. 3 ) . This tumor was initially diagnosed as a variant of a plasmacytoma. T h e biopsy speci mens, seen in consultation, have been vari ously interpreted as plasmacytic sarcoma or lymphoplasmacytic (intermediate) cell sar coma. Examination of the previous biopsy speci mens of 1967 and 1969 showed similar cells, although in some of the previous specimens the cells more closely resembled mature lymphocytes. Amyloid depositon was again a prominent feature. DISCUSSION
This patient has had an 11-year history of an indolent neoplasm involving the con junctiva, eyelid, and orbit as well as the skin and lymph nodes. Histologically and
PATHOLOGY
T h e tumor removed from the left upper eyelid was composed of sheets of small round cells (Fig·. 1). T h e nuclei were large with clumped chromatin ; the cytoplasm was scanty, and stained faintly eosinophilic on hematoxylin and eosin sections. T h e nuclei contained PAS-positive intranuclear inclu sions that were diastase resistant (Fig. 2 ) . Their appearance was consistent with Dutcher bodies. 9 There was considerable vari
Fig. 1 (Jampol, Marsh, Albert, and Zimmer man). Low-power view of tumor demonstrating cell type intermediate between lymphocyte ard plasma cell (hematoxylin and eosin, χ380; AFIP Neg. 74-7234).
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clinically there are similarities to both plasma cell and lymphocytic neoplasms. Interesting features in this case include the presence of monoclonal serum IgA, extensive amyloid deposition in the tumors, and the presence of prominent Dutcher bodies. Although most malignant lymphoid tumors have been subcategorized as lymphosarcoma, Hodgkin's disease, reticulum cell sarcoma, multiple myeloma, lymphatic leukemia, and the like, intermediate forms are seen. For ex-
281
ample, tumors have been described that histologically and clinically appear intermediate between plasma cell tumors and reticulum cell sarcoma10 and also between myeloma and Waldenstrom's macroglobulinemia.11 The disease most commonly associated with monoclonal protein serum spikes of the type seen in our patient is multiple myeloma. The lack of evidence of involvement of the bone marrow and the absence of depression of other serum immunoglobulins after this
Fig. 2 (Jampol, Marsh, Albert, and Zimmerman). High-power view showing presence of intranuclear inclusions or Dutcher bodies (arrows) (hematoxylin and eosin, X600).
282
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Γ
FEBRUARY, 1975
3&S
. J w-
(
JP3
Fig. 3 (Jampol, Marsh, Albert, and Zimmerman). Amyloid stain demonstrating extensive perivascular amyloid deposition within the tumor (Congo red, X600; AFIP Neg. 74-7228). long course are not consistent with this diagnosis. A monoclonal IgA peak is distinctly un usual in malignant lymphoma. None of the 23 patients with lymphoma and monoclonal proteins (M protein) described by Osserman and Takatsuki 12 had IgA proteins. One of the 23 patients with chronic lymphatic leu kemia and M proteins in Hallen's series13 had an IgA type. Two of 57 patients with lymphoma reported by Bachmann14 had an IgA pattern and one had both IgA and IgG. In this same series, only two of the 109 pa tients with an IgA monoclonal protein had lymphoma. In a large series of 678 patients with malignant lymphoma studied by serum electrophoresis, none had IgA peaks15 al though 19 had IgG or IgM peaks. Of 15 patients with lymphoproliferative disorders and a histologie appearance suggestive of immunoglobulin synthesis, one patient showed a monoclonal IgA pattern.16 This patient, like
our patient, had plasmacytoid lymphocytes and Dutcher bodies. Amyloid deposition was a prominent fea ture of the tumor in this case. Evidence ac cumulated in many cases links amyloid to the light chains of immunoglobulins (i.e., Bence Jones proteins). 17 Amyloid may repre sent insoluble complexes of these light chains. Despite prominent amyloid in the tumor, the urinary levels of light chains were low. Isobe and Osserman's 18 recent classifica tion of amyloidosis is based on distribution of this material: Pattern 1 involves the tongue, heart, gastrointestinal tract, muscle, nerves, and skin and is the pattern most commonly found in plasma cell dyscrasias. Pattern 2 refers to involvement of the liver, spleen, kidneys, and adrenals, the distribu tion reported in so-called secondary amy loidosis associated with chronic infection, rheumatoid arthritis, and Hodgkin's disease. Mixtures of the two patterns are also de-
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LYMPHOPLASMACYTOMA
scribed as well as localized deposition of amyloid. Our patient probably best corre sponds to the local pattern with deposition of amyloid seen only in association with the tumor cells. Only three of 100 patients described by Isobe and Osserman18 had this localized pattern. None of these cases were associated with IgA. Only 7% of the 100 patients with amyloidosis had only IgA as an M component as compared to 15% of 300 patients with typical myeloma without amyloidosis from the same institution. Dutcher and Fahey 9 first noted PAS-positive intranuclear inclusion bodies in associa tion with Waldenström's macroglobulinemia. These inclusions also have been reported in multiple myeloma,19 lymphomas, chronic lymphocytic leukemia, and lymphoid hyperplasia.16 In most cases, Dutcher bodies ap pear to represent immunoglobulin20 and are frequently seen in association with abnormal serum or urinary proteins. This was the case with our patient. Dutcher bodies have also been described in certain chronic inflamma tory diseases without protein abnormalities.21 The tumor described here seems to have first appeared in the subconjunctival tissues of the right eye.22 It has subsequently ap peared in the left eyelid and qrbit as well as the skin and lymph nodes. Since IgA is a prominent component of tears,23 this tumor may have originated as a clone of cells from an IgA-producing lymphoid cell in this area. Histologically and clinically, the tumor does not fit into the category of multiple myeloma but instead appears to represent a malignant sarcoma with plasmacytoid lym phocytes. SUMMARY
A 65-year-old white man had an unusual disseminated lymphoid tumor that first ap peared in the subconjunctival tissues of the right eye. The tumor later appeared in the skin, lymph nodes, and left upper eyelid and orbit. A monoclonal serum IgA spike was present although the urine did not contain Bence Jones proteins. The cells of the tumor
283
appeared to be plasmacytoid lymphocytes. Prominent intranuclear inclusions, or Dutcher bodies, were present. Throughout the 11-year history, the patient has been treated only with local excision and radiation. ACKNOWLEDGMENTS
W e thank Vincent Manjoney, M.D., for re ferring this patient and Marvin L. ßears, M.D., for permission to report this case. REFERENCES 1. Zimmerman, L. E. : Lymphoid tumors. In Boniuk, M. (ed.) : Ocular and Adnexal Tumors. St. Louis, C. V. Mosby, 1964, pp. 429-446. 2. Reese, A. B . : Tumors of the Eye, 2nd ed. New York, Harper and Row, 1963, pp. 465-484. 3. Henderson, J. W. : Orbital Tumors. Phila delphia, W. B. Saunders, 1973, pp. 345-408. 4. Little, J. M. : Waldenström's macroglobu linemia in the lacrimai gland. Trans. Am. Acad. Ophthalmol. Otolaryngol. 71:875, 1967. 5. Bouchât, M. J. : Tumeur orbitaire et dysglobulinémie. Bull. Soc. Ophtalmol. Fr. 69:338, 1969. 6. Paufique, L., Girard, P., Schott, B., Creyssel, R., Trillet, M., and Chazot, G. : Pseudolymphome de l'orbite macroglobulino-secrétant associé a une méningolymphomatose avec macroglobulinorachie. Ann. Oculistique 202:1033, 1969. 7. Rodman, H . I., and Font, R. L. : Orbital in volvement in multiple myeloma. Arch. Ophthalmol. 87:30, 1972. 8. Lindström, F . D., Williams, R. C , and Theologides, A. : Urinary light chain excretion in leukaemia and lymphoma. Clin. Exp. Immunol. 5 : 83, 1969. 9. Dutcher, T. F., and Fahey, J. L. : The histopathology of the macroglobulinemia of Waldenström. J. Nati. Cancer Inst. 22:887, 1959. JO. Okano, H., Azar, H. A., and Osserman, E. : Plasmacytic reticulum sarcoma. Am. J. Clin. Pathol. 46:546, 1966. 11. Weintraub, L. R., and Galdabini, J. J. : Monoclonal gammopathy and hyperviscosity. N. Engl. J. Med. 287:243, 1972. 12. Osserman, E. F., and Takatsuki, K. : Plasma cell myeloma. Gamma globulin synthesis and structure. Medicine 42:357, 1963. 13. Hallen, J. : Discrete gammaglobulin com ponents in serum. Clinical study of 150 subjects without myelomatosis. Acta Med. Scand. 462 (Suppl) :1-127, 1966. 14. Bachmann, R. : The diagnostic significance of the serum concentration of pathological pro teins. Acta Med. Scand. 178:801, 1965. 15. Moore, D. M., Migliore, P. J., Schullenberger, C. C , and Alexanian, R. : Monoclonal macro globulinemia in malignant lymphoma. Ann. In tern. Med. 72:43, 1970. 16. Kim, H., Heller, P., and Rappaport, H . :
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Monoclonal gammopathies associated with lymphoproliferative disorders. Am. J. Clin. Pathol. 59: 282, 1973. 17. Franklin, E. C. : The complexity of amyloid. N. Engl. J. Med. 290:512, 1974. 18. Isobe, T., and Osserman, E. F. : Patterns of amyloidosis and their association with plasmacell dyscrasia, monoclonal immunoglobulins and Bence-Jones proteins. N. Engl. T. Med. 290:473, 1974. 19. Brittin, G. M., Tanaka, Y., and Brecher, G. : Intranuclear inclusions in multiple myeloma and macroglobulinemia. Blood 21 :335, 1963.
FEBRUARY, 1975
20. Dutcher, T. F., and Fahey, J. L. : Immunocytochemical demonstration of intranuclear local ization of 18S gamma macroglobulin in macro globulinemia of Waldenström. Proc. Soc. Exp. Biol. Med. 103:452, 1960. 21. Ryan, S. J., Zimmerman, L. E., and King, F. M. : Reactive lymphoid hyperplasia. Trans. Am. Acad. Ophthalmol. Otolaryngol. 76:652, 1972. 22. Morgan, G. : Lymphocytic tumours of the conjunctiva. J. Clin. Pathol. 24:585, 1971. 23. Little, J". M., Centifanto, Y. M., and Kauf man, H. E. : Immunoglobulins in human tears. Am. J. Ophthalmol. 68:898, 1969.
J O H N C. MARSH, M.D., New Haven,
AND DANIEL M. ALBERT,
M.D.
Connecticut
AND LORENZ
E.
ZIMMERMAN,
Washington,
Lymphoid tumors of the orbit represent a challenging diagnostic problem for the ophthalmologist and pathologist. These tu mors include a wide spectrum of diseases from benign lesions (pseudotumors) to ob viously malignant lesions.1·2 According to Henderson,3 malignant lymphoreticular tu mors comprise about 11% of all orbital tumors. Malignant lymphomas (including those associated with Waldenström's macroglobulinemia4-6), multiple myeloma,7 and leukemias all may involve, and even present in, the orbit. We now report on a patient with an unusual conjunctival, eyelid, and orbital tumor associated with subcutaneous masses and lymph node involvement. Inter esting features in this case included (1) ex tensive amyloid deposition within the tumor, (2) a monoclonal IgA serum spike, with negative urinary Bence Jones proteins, (3) tumor cells that cytologically appeared to be intermediate between the lymphocyte and plasma cell, with prominent Dutcher bodies, and (4) an indolent clinical course. From the Department of Ophthalmology and Visual Science ( D r s . Jampol and.Albert), and the Departments of Medicine and Pharmacology (Dr. Marsh), Yale University School of Medicine, New Haven, Connecticut, and the Armed Forces Institute of Pathology, Ophthalmic Pathology Branch (Dr. Zimmerman), Washington, D.C. This work was supported in part by the Ida and Louis Katz Memorial Fund through a grant from Fight for Sight, Inc., New York, and by the Seeing Eye, Inc., Morristown, New Jersey. Dr. Marsh is a Faculty Research Associate, American Cancer Society. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. Reprint requests to Lee M. Jampol, M.D., Illi nois Eye and E a r Infirmary, 1855 W. Taylor St., Chicago, IL 60612.
M.D.
D.C. CASE REPORT
The patient, a 65-year-old white man, was in good health until February 1964, when he de veloped a 10-mm violaceous subconjunctival mass in the region of the right lateral rectus muscle. A biopsy specimen showed a lymphoid tumor. H e was treated with orbital irradiation, receiving 2,500 rads in 12 days with complete clinical re gression of the mass. He then remained well un til November 1967, when he noted the onset of masses in the left epigastric area, right inguinal area, and the right buttocks. A biopsy specimen from the abdominal wall showed lymphosarcoma with extensive amyloid and para-amyloid deposits. H e was treated with 3,500 rads in 18 days to the abdominal wall and buttocks and 3,000 rads in 17 days to the right inguinal lymph nodes. There was dramatic regression of the masses. In June 1969, he noted additional masses on his left back, left breast, and in the left axilla. A biopsy speci men was interpreted as malignant lymphoreticular neoplasm with amyloid deposition. H e was given 3,500 rads to the axilla over 21 days. At this time his hemogram was normal and his albumin/ globulin ratio was 4.6/4.1 g/100 ml, but protein electrophoresis was not done. X-ray films of the bones and chest were normal. In December 1969, he developed herpes zoster of the left axilla and left anterior chest. He was given 1,500 rads to the thoracic spine over the next 36 days for the pain, but since then he continues to have severe pain and hyperesthesia in the left axilla and anterior chest. In 1971, an inguinal hernia was repaired. At this time a calcified mass was observed on an x-ray film of the abdomen in the region of the right kidney. An intravenous pyelogram showed nonvisualization of the right kidney. Bone films showed degenerative arthritis of the spine and generalized osteoporosis, but no lytic lesions. A liver scan was normal. The patient was referred to this hospital in October 1972, with a one-year history of growth in the left upper eyelid. A 30 X 12-mm rubbery firm mass was observed in the left upper eyelid. The best corrected visual acuity was R.E. : 20/25, and L.E. : 20/30. The remainder of the ophthalmic examination including slit-lamp ex amination, ocular tensions, perimetry studies, and ophthalmoscopy was normal. Pertinent findings on general physical examination included two subcu taneous nodules of the chest and an enlarged right
279
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supraclavicular lymph node. There was no bony tenderness or organomegaly. The results of a hemogram, blood urea nitrogen, serum creatinine, liver function tests, serum calcium, and serum phosphorus were all normal. Serum uric acid was 7.9 mg/100 ml. Serum protein electrophoresis showed a spike between the beta- and gammaglobulin portions. Values for individual serum proteins were: albumin, 3.3 g/100 ml; alpha-1 globulin, 0.36 g/100 ml; alpha-2 globulin, 0.S8 g/100 ml; beta globulin, 1.31 g/100 ml; gamma globulin, 0.77 g/100 ml. Serum immunoelectrophoresis re vealed a monoclonal IgA component with kappa light chains. A diffuse elevation of IgM was also present and IgG was normal. Subsequent quanti tative immunoglobulin values were IgG, 1,320 mg/ 100 ml (normal 600-2,000) ; IgA, 1,300 mg/100 ml (normal 60-400) ; IgM, 775 mg/100 ml (normal 20-250). Heat and acetic acid tests of the urine for Bence Jones protein were negative on two occasions. Immunoelectrophoresis of concentrated urine revealed free kappa light chain proteins. The amount was low, however, being less than 100 mg/liter. This value is probably within the normal range.8 The serum viscosity was normal. Serum cold agglutinins and cryoglobulins were negative. The bone marrow was of normal cellularity with a myeloid to an erythroid ratio of 2.3:1 (a normal value). There were 9% lymphocytes and 1% plasma cells, both of normal appearance. Chest and bone x-ray films were unremarkable. A renal arteriogram to evaluate the nonfunctioning right kidney showed an avascular mass consistent with an old perirenal abscess. Under local anesthesia, an excisional biopsy of the left eyelid lesion was attempted but the lesion extended through the orbital septum into the orbit and thus was only partially resected. Subsequently, this area was treated with 2,000 rads over seven days. The patient was last seen March 21, 1974, with no recurrence of the previously treated tumor masses. A biopsy of the enlarged right supraclavicular node showed orly necrotic tissue and planned tissue culture and. immunofluorescent studies of this specimen were not possible. The findings on repeated serum protein electrophoresis have remained unchanged.
FEBRUARY, 1975
ation between the cells in different areas of the tumor but the predominant cell type ap peared to be a plasmacytoid lymphocyte. T h e tumor contained a fibrovascular matrix and scattered reticulum cells. A prominent fea ture of the tumor was the presence of homogeneous eosinophilic material deposited around and within the walls of blood vessels. Stains of these areas with cresyl violet and Congo red for amyloid were positive (Fig. 3 ) . This tumor was initially diagnosed as a variant of a plasmacytoma. T h e biopsy speci mens, seen in consultation, have been vari ously interpreted as plasmacytic sarcoma or lymphoplasmacytic (intermediate) cell sar coma. Examination of the previous biopsy speci mens of 1967 and 1969 showed similar cells, although in some of the previous specimens the cells more closely resembled mature lymphocytes. Amyloid depositon was again a prominent feature. DISCUSSION
This patient has had an 11-year history of an indolent neoplasm involving the con junctiva, eyelid, and orbit as well as the skin and lymph nodes. Histologically and
PATHOLOGY
T h e tumor removed from the left upper eyelid was composed of sheets of small round cells (Fig·. 1). T h e nuclei were large with clumped chromatin ; the cytoplasm was scanty, and stained faintly eosinophilic on hematoxylin and eosin sections. T h e nuclei contained PAS-positive intranuclear inclu sions that were diastase resistant (Fig. 2 ) . Their appearance was consistent with Dutcher bodies. 9 There was considerable vari
Fig. 1 (Jampol, Marsh, Albert, and Zimmer man). Low-power view of tumor demonstrating cell type intermediate between lymphocyte ard plasma cell (hematoxylin and eosin, χ380; AFIP Neg. 74-7234).
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IgA ASSOCIATED LYMPHOPLASMACYTOMA
clinically there are similarities to both plasma cell and lymphocytic neoplasms. Interesting features in this case include the presence of monoclonal serum IgA, extensive amyloid deposition in the tumors, and the presence of prominent Dutcher bodies. Although most malignant lymphoid tumors have been subcategorized as lymphosarcoma, Hodgkin's disease, reticulum cell sarcoma, multiple myeloma, lymphatic leukemia, and the like, intermediate forms are seen. For ex-
281
ample, tumors have been described that histologically and clinically appear intermediate between plasma cell tumors and reticulum cell sarcoma10 and also between myeloma and Waldenstrom's macroglobulinemia.11 The disease most commonly associated with monoclonal protein serum spikes of the type seen in our patient is multiple myeloma. The lack of evidence of involvement of the bone marrow and the absence of depression of other serum immunoglobulins after this
Fig. 2 (Jampol, Marsh, Albert, and Zimmerman). High-power view showing presence of intranuclear inclusions or Dutcher bodies (arrows) (hematoxylin and eosin, X600).
282
AMERICAN JOURNAL OF OPHTHALMOLOGY
Γ
FEBRUARY, 1975
3&S
. J w-
(
JP3
Fig. 3 (Jampol, Marsh, Albert, and Zimmerman). Amyloid stain demonstrating extensive perivascular amyloid deposition within the tumor (Congo red, X600; AFIP Neg. 74-7228). long course are not consistent with this diagnosis. A monoclonal IgA peak is distinctly un usual in malignant lymphoma. None of the 23 patients with lymphoma and monoclonal proteins (M protein) described by Osserman and Takatsuki 12 had IgA proteins. One of the 23 patients with chronic lymphatic leu kemia and M proteins in Hallen's series13 had an IgA type. Two of 57 patients with lymphoma reported by Bachmann14 had an IgA pattern and one had both IgA and IgG. In this same series, only two of the 109 pa tients with an IgA monoclonal protein had lymphoma. In a large series of 678 patients with malignant lymphoma studied by serum electrophoresis, none had IgA peaks15 al though 19 had IgG or IgM peaks. Of 15 patients with lymphoproliferative disorders and a histologie appearance suggestive of immunoglobulin synthesis, one patient showed a monoclonal IgA pattern.16 This patient, like
our patient, had plasmacytoid lymphocytes and Dutcher bodies. Amyloid deposition was a prominent fea ture of the tumor in this case. Evidence ac cumulated in many cases links amyloid to the light chains of immunoglobulins (i.e., Bence Jones proteins). 17 Amyloid may repre sent insoluble complexes of these light chains. Despite prominent amyloid in the tumor, the urinary levels of light chains were low. Isobe and Osserman's 18 recent classifica tion of amyloidosis is based on distribution of this material: Pattern 1 involves the tongue, heart, gastrointestinal tract, muscle, nerves, and skin and is the pattern most commonly found in plasma cell dyscrasias. Pattern 2 refers to involvement of the liver, spleen, kidneys, and adrenals, the distribu tion reported in so-called secondary amy loidosis associated with chronic infection, rheumatoid arthritis, and Hodgkin's disease. Mixtures of the two patterns are also de-
VOL. 79, N O . 2
IgA A S S O C I A T E D
LYMPHOPLASMACYTOMA
scribed as well as localized deposition of amyloid. Our patient probably best corre sponds to the local pattern with deposition of amyloid seen only in association with the tumor cells. Only three of 100 patients described by Isobe and Osserman18 had this localized pattern. None of these cases were associated with IgA. Only 7% of the 100 patients with amyloidosis had only IgA as an M component as compared to 15% of 300 patients with typical myeloma without amyloidosis from the same institution. Dutcher and Fahey 9 first noted PAS-positive intranuclear inclusion bodies in associa tion with Waldenström's macroglobulinemia. These inclusions also have been reported in multiple myeloma,19 lymphomas, chronic lymphocytic leukemia, and lymphoid hyperplasia.16 In most cases, Dutcher bodies ap pear to represent immunoglobulin20 and are frequently seen in association with abnormal serum or urinary proteins. This was the case with our patient. Dutcher bodies have also been described in certain chronic inflamma tory diseases without protein abnormalities.21 The tumor described here seems to have first appeared in the subconjunctival tissues of the right eye.22 It has subsequently ap peared in the left eyelid and qrbit as well as the skin and lymph nodes. Since IgA is a prominent component of tears,23 this tumor may have originated as a clone of cells from an IgA-producing lymphoid cell in this area. Histologically and clinically, the tumor does not fit into the category of multiple myeloma but instead appears to represent a malignant sarcoma with plasmacytoid lym phocytes. SUMMARY
A 65-year-old white man had an unusual disseminated lymphoid tumor that first ap peared in the subconjunctival tissues of the right eye. The tumor later appeared in the skin, lymph nodes, and left upper eyelid and orbit. A monoclonal serum IgA spike was present although the urine did not contain Bence Jones proteins. The cells of the tumor
283
appeared to be plasmacytoid lymphocytes. Prominent intranuclear inclusions, or Dutcher bodies, were present. Throughout the 11-year history, the patient has been treated only with local excision and radiation. ACKNOWLEDGMENTS
W e thank Vincent Manjoney, M.D., for re ferring this patient and Marvin L. ßears, M.D., for permission to report this case. REFERENCES 1. Zimmerman, L. E. : Lymphoid tumors. In Boniuk, M. (ed.) : Ocular and Adnexal Tumors. St. Louis, C. V. Mosby, 1964, pp. 429-446. 2. Reese, A. B . : Tumors of the Eye, 2nd ed. New York, Harper and Row, 1963, pp. 465-484. 3. Henderson, J. W. : Orbital Tumors. Phila delphia, W. B. Saunders, 1973, pp. 345-408. 4. Little, J. M. : Waldenström's macroglobu linemia in the lacrimai gland. Trans. Am. Acad. Ophthalmol. Otolaryngol. 71:875, 1967. 5. Bouchât, M. J. : Tumeur orbitaire et dysglobulinémie. Bull. Soc. Ophtalmol. Fr. 69:338, 1969. 6. Paufique, L., Girard, P., Schott, B., Creyssel, R., Trillet, M., and Chazot, G. : Pseudolymphome de l'orbite macroglobulino-secrétant associé a une méningolymphomatose avec macroglobulinorachie. Ann. Oculistique 202:1033, 1969. 7. Rodman, H . I., and Font, R. L. : Orbital in volvement in multiple myeloma. Arch. Ophthalmol. 87:30, 1972. 8. Lindström, F . D., Williams, R. C , and Theologides, A. : Urinary light chain excretion in leukaemia and lymphoma. Clin. Exp. Immunol. 5 : 83, 1969. 9. Dutcher, T. F., and Fahey, J. L. : The histopathology of the macroglobulinemia of Waldenström. J. Nati. Cancer Inst. 22:887, 1959. JO. Okano, H., Azar, H. A., and Osserman, E. : Plasmacytic reticulum sarcoma. Am. J. Clin. Pathol. 46:546, 1966. 11. Weintraub, L. R., and Galdabini, J. J. : Monoclonal gammopathy and hyperviscosity. N. Engl. J. Med. 287:243, 1972. 12. Osserman, E. F., and Takatsuki, K. : Plasma cell myeloma. Gamma globulin synthesis and structure. Medicine 42:357, 1963. 13. Hallen, J. : Discrete gammaglobulin com ponents in serum. Clinical study of 150 subjects without myelomatosis. Acta Med. Scand. 462 (Suppl) :1-127, 1966. 14. Bachmann, R. : The diagnostic significance of the serum concentration of pathological pro teins. Acta Med. Scand. 178:801, 1965. 15. Moore, D. M., Migliore, P. J., Schullenberger, C. C , and Alexanian, R. : Monoclonal macro globulinemia in malignant lymphoma. Ann. In tern. Med. 72:43, 1970. 16. Kim, H., Heller, P., and Rappaport, H . :
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20. Dutcher, T. F., and Fahey, J. L. : Immunocytochemical demonstration of intranuclear local ization of 18S gamma macroglobulin in macro globulinemia of Waldenström. Proc. Soc. Exp. Biol. Med. 103:452, 1960. 21. Ryan, S. J., Zimmerman, L. E., and King, F. M. : Reactive lymphoid hyperplasia. Trans. Am. Acad. Ophthalmol. Otolaryngol. 76:652, 1972. 22. Morgan, G. : Lymphocytic tumours of the conjunctiva. J. Clin. Pathol. 24:585, 1971. 23. Little, J". M., Centifanto, Y. M., and Kauf man, H. E. : Immunoglobulins in human tears. Am. J. Ophthalmol. 68:898, 1969.
