Multiple Myeloma Orbital Involvement in Sheldon R.
a
Youth
Levin, MD; Abbot G. Spaulding. MD; John
involvement by multiple myand affects older individuals usually. The youngest reported patient in a recent series that cites a median age of 56 years is 30 years of age. The present case involves a 19-year-old pregnant black female subject who complained initially of diplopia and whose presenting sign was proptosis. An extensive medical work-up and electron microscopic study were necessary to establish the diagnosis. \s=b\Orbital
eloma is
rare
(Arch Ophthalmol 95:642-644, 1977)
multiple myeloma three Thisinterestingorbital involvement, case
of
for
is
reasons.
the
These are the young age of the
patient, and the problems encountered in diagnosis.'
Orbital myelomatosis is rare. A series of 465 consecutive orbital tumors contained two cases,- as did another series of 676 orbital tumors.'' A review of the world literature collected a total of 30 cases with an age range from 30 to 89 years,' and only three cases have been added since that report.'" When multiple myeloma is found in unusual locations and in unusually young patients, careful evaluation of clinical and laboratory data is essential, as is the selection of specific procedures. When the cells in biopsy material appear less than typical, it can be confused histologically with reticulum cell sarcoma, amelanotic melanoma, Hodgkin disease, or
Accepted
From the Levin and
for
publication Sept 29, 1976.
Departments of Ophthalmology (Drs Spaulding)
and
Pathology (Dr
Wirman), University of Cincinnati College of Medicine, Cincinnati. Reprint requests to Department of Ophthalmology, College of Medicine, University of Cincinnati, 231 Bethesda Ave, Cincinnati, OH 45267 (Dr Spaulding).
A.
Wirman, MD
iindill'erentiated carcinoma, and in such instances electron microscopy may be necessary to establish a diagnosis.7 REPORT OF A CASE An 18-year-old woman came to the Eye Clinic in December 1975 with a two-week history of bulging of the left upper lid and a one-week history of double vision. She was 12 weeks pregnant at this initial
visit.
The ophthalmoscopic examination revealed a corrected visual acuity of 20/25 OD and 20/25 OS. There was fuliness laterally in the left upper lid and brow area. Here a palpable mass, nontender and rubbery, extended below the superior orbital rim. There was 3 mm of proptosis of the left globe. Extraocular muscle movements demonstrated a marked limitation of upward gaze and there was 6 prism diopters of left hypotropia in the primary position (Fig 1). Intraocular pressures were equal and normal. The optic nerve head and macular area of the left eye were normal but slight indentation of the globe was noted equatorially from 12 o'clock to 3 o'clock. Central and peripheral fields were full. Further outpatient evaluation included a K-scan ultrasound examination that demonstrated a translucent orbital lesion (Fig 2). Roentgenograms of the skull and tomograms of the orbit revealed a destructive lesion extending into the roof of the orbit and involving the frontal bone (Fig 3). A chest roentgenogram showed a destructive lesion in the outer third of the right clavicle and a suspicious area in the left distal clavicle (Fig 4). These clavicular lesions had not been present 18 months earlier on a routine chest film. Following hospital admission to the Eye Service, a computerized axial tomogram (EMI scan) was performed and showed a smoothly outlined lesion emanating from the cranial vault in a sharply circumscribed fashion (Fig 5). Results of the general physical examination, with the exception of the ophthalmological part, were unremarkable. Pertinent laboratory findings
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
as follows: WBCs, 5,500/cu mm; hematocrit, 30%; erythrocyte sedimentation rate, 54 mm/hr; calcium 9.3 mg/100 ml; alkaline phosphatase, 36 units; total protein, 8.3 gm/100 ml; albumin/globulin ratio, 3.4/4.9. A biopsy was performed on the third hospital day and included both soft and were
bony tissue. Light microscopic examina-
tion of formalin fixed tissue showed that the lesion consisted of sheets of small uniform round to polygonal cells with central nuclei. Nuclear pleomorphism was moderate, and the chromatin pattern was generally diffuse, Small central nucleoli were present (Fig (i). Material submitted for electron microscopic study was unsuitable because of extensive fixation artifact. The lesion was considered to be a small cell undill'erentiated sarcoma. The differential diagnosis included embryonal rhabdomyosarcoma, Ewing sarcoma, and lymphoma. Consultation from the Armed Forces Institute of Pathology, however, noted that a striking plasmaeytic differentiation with bone involvement was present and, in addition, believed that an inflammatory process could not be completely ruled out. Bone and gallium scans did not reveal any additional bone lesions. A bone marrow biopsy revealed no abnormalities. An open biopsy of the right clavicle was performed and the histopathologic picture was identical to the orbital tumor. Treatment consisting of dactinomycin (actinomycin D), 500 mg daily for six days, and irradiation to the orbit (2,700 rails) was started. Following irradiation, there was full return of the function of the extraocular muscles and a gradual subsidence of
Fig 1.—Patient on admission showing complete absence of elevation of left eye in eyes up position of gaze.
F'9 2.—Ultrasound cent
area
(2)
scan
outside
orbital tissue (3).
shows
globe (1)
a translubut within
Fig 3.—Skull roentgenogram shows an of bone destruction (arrow) extending into roof of orbit and involving frontal
area
bone.
Fig 4.—Distal area
end of right clavicle shows of bone destruction (arrow).
reticulum. Those cells sectioned in the proper plane had prominent perinuclear golgi zones, whose cisternae were filled with electron dense material (Fig 8). The ultrastructure of these cells was characteristic of the malignant plasma cells of multiple myeloma.""
endoplasmic
F'9 5.—Computerized
axial tomogram Dec 20, 1975: Left, Uniform density emanating 'r°m lateral superior orbital wall, occupying lateral superior orbit. Center, At intensity Used to demonstrate bone, notching of frontal bone laterally indicated loss or destruction of bone. Right, The right globe and orbit are demonstrated well. Image of left globe is blurred by a density lateral and superior to it.
A subsequent serum protein electrophoresis had a monoclonal IgG spike, and trace amounts of Bence Jones protein were demonstrated in the urine by immunofluorescence. A sternal mass was noted, making a total of four foci of probable
plasmacytomas. Treatment was changed to
regimen for multiple myeloma. Chemotherapy consisted of melphalan, 16 mg daily for four days, and prednisone, 80 mg daily for four days. After the initial course a
of treatment, improvement was noted in several areas. The sternal mass receded, the anemia improved, and the protein spike on serum electrophoresis decreased. Four months after the patient started therapy for multiple myeloma, her response was thought to be excellent, and the disease appeared to be in remission. The serum protein electrophoresis was within normal limits and the anemia was improving. There was no evidence of any additional bony involvement. On May 27, a premature infant boy was delivered. The birth weight was 2,522 gm, and the Apgar score was nine. Both mother and child have done well.
COMMENT
classic
case
ple myeloma,
the
In
F¡9 6.—Photomicrograph showing nuclei. Occasional nucleoli and
e°sin, X160).
tne proptosis (Fig 7).
Material
small to moderate sized cells with oval to round chromatin clumping are present (hematoxylin-
some
from the clavicular biopsy, 'ixcd in 4% buffered glutaraldehyde, was sUidied by electron microscopy. All cells were strikingly similar. They were ovoid to Polygonal with irregularly rounded nuclei,
usually eccentrically located. Moderate irregularity of the nuclear outline was seen. The cytoplasm of all cells was filled with plates of granular endoplasmic reticulum, usually in parallel lamellae. Elongated mitochondria
were
abundant within the
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
a
systemic multipatient would be
of
between 40 and 70 years old and would have generalized fatigue, weight loss, and pathologic fractures.'" Laboratory data would reveal anemia, increased plasma proteins due to a monoclonal gammopathy, and Bence Jones proteinuria. The bone marrow biopsy would reveal an increase in plasma cells. Multiple myelomatosis can ef-
Fig 7.—Patient after irradiation therapy showing almost complete return of eleva-
tion of left eye.
feet the eye in many ways. Involvement of the conjunctiva,' ciliary body," cornea,'- sciera, choroid, and iris" have all been described. The retina may show punctate or flameshaped hemorrhages. Central retinal artery or vein thrombosis have been reported." There may be papilledema as well as ocular nerve palsies due to intracranial extension. The sixth cranial nerve is the most commonly involved. There may also be involvement of the optic pathways due to invasion of the base of the skull or chiasmal compression. Recently, a case was reported with metastatic bacterial endophthalmitis.'"' When there is the rare occurrence of multiple myeloma in the orbit, the most common clinical manifestation is proptosis. Visual impairment is the next most
common
feature, varying
from total blindness to only slight decrease in vision. Unlike other malignant orbital neoplasms, pain is rarely
experienced.1"
The median survival rate when not than two localized plasmacytomas are present is eight years, whereas the median survival rate for the treated generalized disease is only about two years." Irradiation therapy (4,000 rads) is usually effective for localized disease, while chemotherapy is indicated in generalized disease. Several factors in this case either more
Fig 8.—Electron microscopic study showing eccentric nuclei (stars) with small nucleoliNote abundant plates of granular endoplasmic reticulum (arrows) in parallel lamellae, filling the cytoplasm. Elongated mitochondria lie within endoplastic reticulum (x 4,100).
delayed
or made the diagnosis difficult. The reversal of the albumin/ globulin ratio was initially overlooked. Findings from routine Bence Jones proteinuria studies were continually normal, and only later in the evaluation were trace amounts detected by the immunofluorescent technique. The bone marrow studies were noncontributory. Histologieally, the orbital and clavicular plasmacytomas were poorly differentiated, and a diagnosis could not be made with certainty on light microscopy. Eventually, ultrastructural studies showed the lesion was composed of malignant plasma cells, suggesting the diagnosis of multiple myeloma, which in turn was supported by laboratory confirmation of an IgG gammopathy and Bence Jones proteinuria. The patient's ther-
was changed accordingly with good response. Multiple myeloma must now be
apy
included in the differential diagnosis of orbital lesions .in young patients. The careful evaluation of these patients should proceed in the same manner as for any orbital lesion. The local studies, however, should not exclude a similar careful systemic evaluation. The importance of all of this cannot be overemphasized. This investigation was supported in part Ohio Lions Eye Research Foundation.
by the
Nonproprietary Names and Trademarks of Drugs
Dactinomycin—Cosmegen. Mv\]>ha\a.n-Alkcran.
References 1. Rodman HI, Font RL: Orbital involvement in multiple myeloma: A review of the literature and report of three cases. Arch Ophthalmol 87:30\x=req-\ 35, 1972. 2. Henderson JW: Orbital Tumors. Philadelphia, WB Saunders Co, 1973, pp 400-404. 3. Offret G: Les Tumeurs Primitives de l'Orbite Leur Traitement. Paris, Masson & Cie, 1951. 4. Benjamin F, Taylor H, Spindler J: Orbital and conjunctival involvement in multiple myeloma. Am J Clin Pathol 63:811-817, 1975. 5. Darbani BS, et al: Bilateral orbit plasmacytoma. Indiana J Ophthalmol 20:28-30, 1972. 6. McFadzean RM: Orbital plasma cell myeloma. Br J Ophthalmol 59:164-165, 1975.
7. Pasco HR, Dorfman RF: Extramedullary plasma cytome of the submaxillary gland. Am J
Clin Pathol 51:501-507, 1969. 8. Zucker-Franklin D: Cellular structure and function in normal and neoplastic lymphoid cells. Arch Intern Med 135:55-60, 1975. 9. Curtis SK, Propp R, Cowden RR, et al: Ultrastructure of a human malignant IgA-pro-
Arch Ophthalmol 61:541-546, 1959. 13. Brownstein M: Ocular involvement in
multiple myeloma.
multiple myeloma. Arch Ophthalmol 55:188-192, 1956. 14. Clarke E:
Ophthalmological complications
of multiple myelomatosis. Br J 39:233-236, 1955.
Ophthalmol.
ducing plasmacytoma. Exp Mol Pathol 22:386-399,
TR, Spencer VVH: Ocular findings multiple myeloma. Arch Ophthalmol 91:110\x=req-\ 113, 1974. 16. Clarke E: Plasma cell myeloma of the orbit. Br J Ophthalmol 37:543-554, 1953.
1965.
26:38-49, 1976.
1975. 10. Wintrobe MM: Clinical Hematology. Philadelphia, Lea & Febiger, 1974, pp 1605-1610. 11. Ashton N: Ocular changes in multiple myelomatosis. Arch Ophthalmol 73:487-494, 12. Aronson SB, Shaw R: Corneal
crystals
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
in
15. Baker
in
17. Alexanian R: Plasma cell
neoplasma. CA
a
Youth
Levin, MD; Abbot G. Spaulding. MD; John
involvement by multiple myand affects older individuals usually. The youngest reported patient in a recent series that cites a median age of 56 years is 30 years of age. The present case involves a 19-year-old pregnant black female subject who complained initially of diplopia and whose presenting sign was proptosis. An extensive medical work-up and electron microscopic study were necessary to establish the diagnosis. \s=b\Orbital
eloma is
rare
(Arch Ophthalmol 95:642-644, 1977)
multiple myeloma three Thisinterestingorbital involvement, case
of
for
is
reasons.
the
These are the young age of the
patient, and the problems encountered in diagnosis.'
Orbital myelomatosis is rare. A series of 465 consecutive orbital tumors contained two cases,- as did another series of 676 orbital tumors.'' A review of the world literature collected a total of 30 cases with an age range from 30 to 89 years,' and only three cases have been added since that report.'" When multiple myeloma is found in unusual locations and in unusually young patients, careful evaluation of clinical and laboratory data is essential, as is the selection of specific procedures. When the cells in biopsy material appear less than typical, it can be confused histologically with reticulum cell sarcoma, amelanotic melanoma, Hodgkin disease, or
Accepted
From the Levin and
for
publication Sept 29, 1976.
Departments of Ophthalmology (Drs Spaulding)
and
Pathology (Dr
Wirman), University of Cincinnati College of Medicine, Cincinnati. Reprint requests to Department of Ophthalmology, College of Medicine, University of Cincinnati, 231 Bethesda Ave, Cincinnati, OH 45267 (Dr Spaulding).
A.
Wirman, MD
iindill'erentiated carcinoma, and in such instances electron microscopy may be necessary to establish a diagnosis.7 REPORT OF A CASE An 18-year-old woman came to the Eye Clinic in December 1975 with a two-week history of bulging of the left upper lid and a one-week history of double vision. She was 12 weeks pregnant at this initial
visit.
The ophthalmoscopic examination revealed a corrected visual acuity of 20/25 OD and 20/25 OS. There was fuliness laterally in the left upper lid and brow area. Here a palpable mass, nontender and rubbery, extended below the superior orbital rim. There was 3 mm of proptosis of the left globe. Extraocular muscle movements demonstrated a marked limitation of upward gaze and there was 6 prism diopters of left hypotropia in the primary position (Fig 1). Intraocular pressures were equal and normal. The optic nerve head and macular area of the left eye were normal but slight indentation of the globe was noted equatorially from 12 o'clock to 3 o'clock. Central and peripheral fields were full. Further outpatient evaluation included a K-scan ultrasound examination that demonstrated a translucent orbital lesion (Fig 2). Roentgenograms of the skull and tomograms of the orbit revealed a destructive lesion extending into the roof of the orbit and involving the frontal bone (Fig 3). A chest roentgenogram showed a destructive lesion in the outer third of the right clavicle and a suspicious area in the left distal clavicle (Fig 4). These clavicular lesions had not been present 18 months earlier on a routine chest film. Following hospital admission to the Eye Service, a computerized axial tomogram (EMI scan) was performed and showed a smoothly outlined lesion emanating from the cranial vault in a sharply circumscribed fashion (Fig 5). Results of the general physical examination, with the exception of the ophthalmological part, were unremarkable. Pertinent laboratory findings
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
as follows: WBCs, 5,500/cu mm; hematocrit, 30%; erythrocyte sedimentation rate, 54 mm/hr; calcium 9.3 mg/100 ml; alkaline phosphatase, 36 units; total protein, 8.3 gm/100 ml; albumin/globulin ratio, 3.4/4.9. A biopsy was performed on the third hospital day and included both soft and were
bony tissue. Light microscopic examina-
tion of formalin fixed tissue showed that the lesion consisted of sheets of small uniform round to polygonal cells with central nuclei. Nuclear pleomorphism was moderate, and the chromatin pattern was generally diffuse, Small central nucleoli were present (Fig (i). Material submitted for electron microscopic study was unsuitable because of extensive fixation artifact. The lesion was considered to be a small cell undill'erentiated sarcoma. The differential diagnosis included embryonal rhabdomyosarcoma, Ewing sarcoma, and lymphoma. Consultation from the Armed Forces Institute of Pathology, however, noted that a striking plasmaeytic differentiation with bone involvement was present and, in addition, believed that an inflammatory process could not be completely ruled out. Bone and gallium scans did not reveal any additional bone lesions. A bone marrow biopsy revealed no abnormalities. An open biopsy of the right clavicle was performed and the histopathologic picture was identical to the orbital tumor. Treatment consisting of dactinomycin (actinomycin D), 500 mg daily for six days, and irradiation to the orbit (2,700 rails) was started. Following irradiation, there was full return of the function of the extraocular muscles and a gradual subsidence of
Fig 1.—Patient on admission showing complete absence of elevation of left eye in eyes up position of gaze.
F'9 2.—Ultrasound cent
area
(2)
scan
outside
orbital tissue (3).
shows
globe (1)
a translubut within
Fig 3.—Skull roentgenogram shows an of bone destruction (arrow) extending into roof of orbit and involving frontal
area
bone.
Fig 4.—Distal area
end of right clavicle shows of bone destruction (arrow).
reticulum. Those cells sectioned in the proper plane had prominent perinuclear golgi zones, whose cisternae were filled with electron dense material (Fig 8). The ultrastructure of these cells was characteristic of the malignant plasma cells of multiple myeloma.""
endoplasmic
F'9 5.—Computerized
axial tomogram Dec 20, 1975: Left, Uniform density emanating 'r°m lateral superior orbital wall, occupying lateral superior orbit. Center, At intensity Used to demonstrate bone, notching of frontal bone laterally indicated loss or destruction of bone. Right, The right globe and orbit are demonstrated well. Image of left globe is blurred by a density lateral and superior to it.
A subsequent serum protein electrophoresis had a monoclonal IgG spike, and trace amounts of Bence Jones protein were demonstrated in the urine by immunofluorescence. A sternal mass was noted, making a total of four foci of probable
plasmacytomas. Treatment was changed to
regimen for multiple myeloma. Chemotherapy consisted of melphalan, 16 mg daily for four days, and prednisone, 80 mg daily for four days. After the initial course a
of treatment, improvement was noted in several areas. The sternal mass receded, the anemia improved, and the protein spike on serum electrophoresis decreased. Four months after the patient started therapy for multiple myeloma, her response was thought to be excellent, and the disease appeared to be in remission. The serum protein electrophoresis was within normal limits and the anemia was improving. There was no evidence of any additional bony involvement. On May 27, a premature infant boy was delivered. The birth weight was 2,522 gm, and the Apgar score was nine. Both mother and child have done well.
COMMENT
classic
case
ple myeloma,
the
In
F¡9 6.—Photomicrograph showing nuclei. Occasional nucleoli and
e°sin, X160).
tne proptosis (Fig 7).
Material
small to moderate sized cells with oval to round chromatin clumping are present (hematoxylin-
some
from the clavicular biopsy, 'ixcd in 4% buffered glutaraldehyde, was sUidied by electron microscopy. All cells were strikingly similar. They were ovoid to Polygonal with irregularly rounded nuclei,
usually eccentrically located. Moderate irregularity of the nuclear outline was seen. The cytoplasm of all cells was filled with plates of granular endoplasmic reticulum, usually in parallel lamellae. Elongated mitochondria
were
abundant within the
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
a
systemic multipatient would be
of
between 40 and 70 years old and would have generalized fatigue, weight loss, and pathologic fractures.'" Laboratory data would reveal anemia, increased plasma proteins due to a monoclonal gammopathy, and Bence Jones proteinuria. The bone marrow biopsy would reveal an increase in plasma cells. Multiple myelomatosis can ef-
Fig 7.—Patient after irradiation therapy showing almost complete return of eleva-
tion of left eye.
feet the eye in many ways. Involvement of the conjunctiva,' ciliary body," cornea,'- sciera, choroid, and iris" have all been described. The retina may show punctate or flameshaped hemorrhages. Central retinal artery or vein thrombosis have been reported." There may be papilledema as well as ocular nerve palsies due to intracranial extension. The sixth cranial nerve is the most commonly involved. There may also be involvement of the optic pathways due to invasion of the base of the skull or chiasmal compression. Recently, a case was reported with metastatic bacterial endophthalmitis.'"' When there is the rare occurrence of multiple myeloma in the orbit, the most common clinical manifestation is proptosis. Visual impairment is the next most
common
feature, varying
from total blindness to only slight decrease in vision. Unlike other malignant orbital neoplasms, pain is rarely
experienced.1"
The median survival rate when not than two localized plasmacytomas are present is eight years, whereas the median survival rate for the treated generalized disease is only about two years." Irradiation therapy (4,000 rads) is usually effective for localized disease, while chemotherapy is indicated in generalized disease. Several factors in this case either more
Fig 8.—Electron microscopic study showing eccentric nuclei (stars) with small nucleoliNote abundant plates of granular endoplasmic reticulum (arrows) in parallel lamellae, filling the cytoplasm. Elongated mitochondria lie within endoplastic reticulum (x 4,100).
delayed
or made the diagnosis difficult. The reversal of the albumin/ globulin ratio was initially overlooked. Findings from routine Bence Jones proteinuria studies were continually normal, and only later in the evaluation were trace amounts detected by the immunofluorescent technique. The bone marrow studies were noncontributory. Histologieally, the orbital and clavicular plasmacytomas were poorly differentiated, and a diagnosis could not be made with certainty on light microscopy. Eventually, ultrastructural studies showed the lesion was composed of malignant plasma cells, suggesting the diagnosis of multiple myeloma, which in turn was supported by laboratory confirmation of an IgG gammopathy and Bence Jones proteinuria. The patient's ther-
was changed accordingly with good response. Multiple myeloma must now be
apy
included in the differential diagnosis of orbital lesions .in young patients. The careful evaluation of these patients should proceed in the same manner as for any orbital lesion. The local studies, however, should not exclude a similar careful systemic evaluation. The importance of all of this cannot be overemphasized. This investigation was supported in part Ohio Lions Eye Research Foundation.
by the
Nonproprietary Names and Trademarks of Drugs
Dactinomycin—Cosmegen. Mv\]>ha\a.n-Alkcran.
References 1. Rodman HI, Font RL: Orbital involvement in multiple myeloma: A review of the literature and report of three cases. Arch Ophthalmol 87:30\x=req-\ 35, 1972. 2. Henderson JW: Orbital Tumors. Philadelphia, WB Saunders Co, 1973, pp 400-404. 3. Offret G: Les Tumeurs Primitives de l'Orbite Leur Traitement. Paris, Masson & Cie, 1951. 4. Benjamin F, Taylor H, Spindler J: Orbital and conjunctival involvement in multiple myeloma. Am J Clin Pathol 63:811-817, 1975. 5. Darbani BS, et al: Bilateral orbit plasmacytoma. Indiana J Ophthalmol 20:28-30, 1972. 6. McFadzean RM: Orbital plasma cell myeloma. Br J Ophthalmol 59:164-165, 1975.
7. Pasco HR, Dorfman RF: Extramedullary plasma cytome of the submaxillary gland. Am J
Clin Pathol 51:501-507, 1969. 8. Zucker-Franklin D: Cellular structure and function in normal and neoplastic lymphoid cells. Arch Intern Med 135:55-60, 1975. 9. Curtis SK, Propp R, Cowden RR, et al: Ultrastructure of a human malignant IgA-pro-
Arch Ophthalmol 61:541-546, 1959. 13. Brownstein M: Ocular involvement in
multiple myeloma.
multiple myeloma. Arch Ophthalmol 55:188-192, 1956. 14. Clarke E:
Ophthalmological complications
of multiple myelomatosis. Br J 39:233-236, 1955.
Ophthalmol.
ducing plasmacytoma. Exp Mol Pathol 22:386-399,
TR, Spencer VVH: Ocular findings multiple myeloma. Arch Ophthalmol 91:110\x=req-\ 113, 1974. 16. Clarke E: Plasma cell myeloma of the orbit. Br J Ophthalmol 37:543-554, 1953.
1965.
26:38-49, 1976.
1975. 10. Wintrobe MM: Clinical Hematology. Philadelphia, Lea & Febiger, 1974, pp 1605-1610. 11. Ashton N: Ocular changes in multiple myelomatosis. Arch Ophthalmol 73:487-494, 12. Aronson SB, Shaw R: Corneal
crystals
Downloaded From: http://archopht.jamanetwork.com/ by a Western University User on 06/08/2015
in
15. Baker
in
17. Alexanian R: Plasma cell
neoplasma. CA
