Case Reports
Thyroid involvement in multiple myeloma R. Patel* Registrar in Medical Oncology, Department of Medical Oncology, Royal Perth Hospital, WA.
E. Bayliss Medical Oncologist, Department of Medical Oncology, Royal Perth Hospital, WA.
J. Trotter Medical Oncologist, Department of Medical Oncology, Royal Perth Hospital, WA.
Abstract: Involvement of the thyroid gland by plasma cell neoplasms is a rare occurrence. Two modes of presentation are described; firstly as part of disseminated myeloma and secondly, as an isolated plasma cell neoplasm of the thyroid as the only evidence of disease. We wish to describe two cases of thyroid involvement as part of disseminated disease. (Aust NZ J Med 1992; 22: 139-141.) Key words: Multiple myeloma, thyroid, plasma cell neoplasm.
CASE REPORTS Case One A 70-year-old retired farmer presented in June, 1989 with a six month history of progressive hoarseness. Three months previously a fall at work resulted in mid to low thoracic back pain. The pain became worse. He also complained of 2 kg weight loss, cold intolerance and general fatigue. He had a past history of urinary tract infection with septicaemia. He was taking no medication. He admitted to two episodes of streaky haemoptysis in June and January of 1989. Examination revealed a hard, bilaterally enlarged thyroid gland with no associated lymphadenopathy. He was tender to percussion over his left ribs. The remainder of the physical examination was normal. A skeletal survey showed lytic lesions above the left mastoid, in the 5th, 6th and 7th ribs, in multiple thoracic vertebrae, in neck and shafi of the left femur and a large deposit in the left acetabulum. A thoracic C T scan demonstrated multiple expansile deposits in the ribs and vertebrae and a soft tissue mass at the left of T 4 with spinal canal encroachment. Biochemical testing showed normal urea and electrolytes and liver calcium function tests. Uric acid 0.3 mmol/L (0.18-0.49 mmol), 2.43 mmol/L (2.25-2.65 mmollL). His thyroid function tests were T 4 83 nmol/L (70-140 nmolL), TSH 1.1 m U L (0.5-6.0 mU/L). A quantitative electrophoresis showed his alpha-1 globulin to be 3 g/L, alpha-2 globulin 8 g/L, beta globulin 10 glL, gamma globulin 2 g/L (a paraprotein band was detected at 29 g/L. IEP proved this to be IgG kappa.) Immunoglobulin concentrations were IgG 0.4 g/’L (6-14.3 gL), IgA 0.9 g/L (0.65-3.4). Bence Jones protein was detected but not quantitated. Full blood count showed the haemoglobin to be 155 g/L, the white cell count 6.4 x 10p/L, platelets 340 x 109/Land ESR 35 mm per hour.
Fine needle aspirates from both lobes of the thyroid and one from the ribs demonstrated large numbers of malignant plasma cells. The nuclei were centrally placed with coarsely granular chromatin and nucleoli. The cytoplasm was amphophilic and at times granular. The changes were felt to be consistent with multiple myeloma. Under dexamethasone cover, the patient received radiotherapy to his thoracic spine resulting in resolution of the back pain. Subsequently he was started on three weekly courses of cyclophosphamide 150 mg daily for five days in association with prednisolone 100 mg daily. His thyroid rapidly shrank and was no longer palpable. He has remained well without recurrence of bone pain or thyroid enlargement. The paraprotein hand fell to a low of 12 g/L after several cycles of therapy, but in July 1991 was again measured at 29 g/L. He has not had any recent Bence Jones protein estimations. Case Two A 65-year-old man was referred in July, 1985 to the Combined Head and Neck Clinic with a blocked nose. He was found to have an ethmoid mass. Intra-nasal antrostomy and partial ethmoid clearance were performed with histological examination revealing a plasmacytoma. He received radiotherapy to the atfected ethmoid sinus because of C T evidence of residual disease in the antrum and ethmoid. There was no intracranial disease. Bence Jones protein, quantitative electrophoresis, specific X-rays of his ribs and bone marrow examination showed no evidence of disease elsewhere. In February, 1987 he presented with a mass which was fured to his left mandible just anterior to the ramus. Fine needle cytology and operative biopsy confirmed a plasmacytoma. Further investigations showed no evidence of diffise disease apart from possible deposits in the left 9th and 10th ribs.
Reprinz requests lo: Dr R. Patel, Department of Nuclear Medicine, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia. *Current address: Department of Nuclear Medicine, Royal Prince Alfred Hospital, Sydney, NSW. THYROID DISEASE IN MYELOMA
Aust NZ J Med 1992; 22
139
TABLE 1 Reported cases of Thyroid Involvement by Plasma Cell Neoplasm Period Period between followed myeloma DX after thyroid to thyroid & involvement outcome
Tre:Az?j for
Case No Authors
Age' Sex
1 Voegt 2 Shaw & Smith 3 Hazard & Schildecker
? 50 F
0 0
?
54 M
0
16v DOC
(recurrence 10 yrs later) Lt TX, FIT 3750 r
4 Hazard & Shildecker 5 Barton & Farmer 6 Castlemar 7 Willis 8 Guerrier et a/, 9 More et a/, 10 More et a/.
71 M 77 F 62 M 64 F 54 F 51 F 44 F
0
5YA 3 y 4
i t TX, RT 1700 r
11 More et a/ 12 Oberkircher et a/ 13 Sasse et a/. 14 Shirnaoka et a/. * 15 Shimoaka et a/. * 16 Shirnaoka et a/.' 17 Shimoaka et a/. *
50 M 82 F 70 M 58 F 69 M 62 M 66 M
0
3Y 2rn 0
0 0
0
0 0 2y 3y 7y 0
7
DOD 10 m A I Y A 3YA
4yDOD 4 y DOC 10 d DOC 3 m A 5 m DOD 7 y DOD 8YA
Bone Bone Bence Parapro- Antithyroid Remarks lesion marrow Jones teinernia Antibodies
-
-
TX, RT
TX TX
TX TX, T4 TX (recurrence 1 yr later) RT on T4 RTonDT radioiodine TX,R 2300 r RT2600 r Lt TX, RT
-
+ +
-
-
-
-
+
+
-
+ + + -
+ + + + -
+ -
-
-
+ -
-
-
+ + + + + -
-
Ca breast
-
-
Cacecum
m-months,y-years;A-alive at the time of the report; DOD-diedof disease; DOC-diedof other cause, TX-thyroidectomv;RT-radiationtherapy; T4-thvroxine, DT-dexiccatedthyroid *Modified from Shimoaka et a / , Cancer Vol 41 March 1978, 1140 6
Radiotherapy was administered to the mandibular lesion, but later that year the patient developed a further deposit in the right maxilla. He received chemotherapy with cyclophosphamide and prednisolone which produced an incomplete response. In October, 1987 his disease had progressed with involvement of the right antrum as well as multiple skeletal lesions. He required irradiation to the right antrum and a number of painful bony sites. Quantitative immunoglobulin estimation revealed normal IgG and IgM. The IgA was measured at 7.8 glL (0.65-3.4). Immunoelectrophoresis revealed two low concentration abnormal bands in the gamma region containing monoclonal IgA lambda. A large right femoral deposit required prophylactic internal fixation. In February, 1988 a mass at the right side of the neck became apparent over 24 hours with examination revealing a hard 4.3 cm nontender mass in the right lobe of the thyroid. Fine needle aspiration revealed plasmacytoid cells resembling those seen in previous biopsies and consistent with multiple myeloma in the thyroid. A technetium - 99m scan of the thyroid showed poor delineation of the thyroid presumably due to a blocking agent with 0.3% of the administered dose being taken up at 26 minutes post injection. A non-functioning area corresponded to the palpable thyroid nodule. No thyroid function tests were done, although the patient was clinically euthyroid. He was treated with Melphalan and prednisolone. His myeloma in general and the thyroid nodule in particular failed to respond and he required external beam radiotherapy to the thyroid mass, receiving 16 Gray in eight fractions over 15 days, and resulting in shrinkage of the thyroid mass. He continued to deteriorate however and died in June, 1988.
DISCUSSION Involvement of the thyroid gland by plasma cell neoplasms
140
is rare. A search of the available literature could find only 17 cases of thyroid gland involvement and the nature of this involvement varied considerably from case to case. In some cases the development of thyroid disease was a new manifestation in the setting of well established widespread myeloma. In other cases the thyroid gland appeared clinically normal during life, but autopsy examination revealed areas of disease. In yet other cases, the thyroid was the site for a primary extra medullary plasma cell neoplasm with or without adjacent lymph node metastases, but without evidence of systemic disease. Both of the cases discussed in the current report demonstrated myelomatous involvement of the thyroid preceded by widely disseminated disease elsewhere. Four cases of plasma cell involvement of the thyroid were reported by Shimaoka et al. They covered all the different modes of presentation mentioned above. They described the plasma cell tumours in their patients to be radiosensitive and that only modest doses of radiation were required for good control. In our report, one of our patients did not require radiation as he developed a local complete response to chemotherapy, although the other was refractory to cytotoxics and required irradiation which resulted in tumour response. The overall number of cases in the literature is too small to indicate whether the presence of thyroid involvement has any prognostic significance. The differential diagnosis in such cases would include lymphoma with plasmacytoid differentiation. However, this is a rare finding with few case reports in the literature.
Aust NZ J Med 1,992; 22
PATEL ET AL.
The usual therapeutic approach in patients presenting with apparently solitary plasmacytoma is to treat the lesion locally with irradiation and. then to wait and watch until the disease occurs elsewhere. If the radiotherapy is not successful in obliterating the lesion chemotherapy is used. Our case reports would seem to indicate, however, that it is reasonable to assess the local effect of systemic therapy before resorting to local radiotherapy.
I
Date of submission: 17 October 1990
References 1. Shimaoka K, Gailani S, Tsukada Y, Barcos M. Plasma cell neoplasm involving the thyroid. Cancer 1976; 41: 1140-6. 2. Hayes DW, Bennett WA, Heck FJ. Extramedullary lesions in multiple myeloma. Arch Pathol 1952; 53: 262-78. 3. Craie: I. Plasmacytoma of the thyroid. J Clin Pathol 1968; 21: 661-7.
Corrigendum munuciunai large granurar iympnucyre pruilrerariun in
DLC
wim
HTLV-I seroreactivity Y. Marlton, K. I aylor, J. McLormacK Mater Misericordiae Hospitals, Brisbane, Qld.
3.
Elliott
Queensland University of Technology, Brisbane, Qld.
Abstract: A 60-year-oldpart Aboriginal woman was observed to develop severe neutropenia and a large granular lymphocyte (LGL) proliferation five years after the diagnosis of s stemic lupus erythematosus (SLE). Monoclonality of the CD3 + ,CD4 - ,CD8 LGL population was conirmed using the novel approach of X-linked restriction fragment length polymorphism (RFLP) analysis. Indeterminate HTLV-I serology was present. The patient responded to steroid therapy. LGL proliferation in the setting of SLE and the use of X-linked RFLP analysis to define LGL clonality have not previously been reported. (Aust NZ J Med 1992; 22: 54-55.)
+
Key words: Large granular lymphocyte, SLE, HTLV-I, X-linked clonal analysis.
Figure 1 pertaining to the above article and published in Aust NZ J Med 1992; 22: 54-5 was published with the omission of the half tone plate. It is now reproduced below.
Figure 1: X-linked analysis with the HPRT gene probe showing heterozygosity for BamHl (lane 1+ 3). With HpaII digestion, the LGL are shown to be monoclonal (lane 2) and control tissue polyclonal (lane 4).
Aust NZ J Med 1992; 22
141
Thyroid involvement in multiple myeloma R. Patel* Registrar in Medical Oncology, Department of Medical Oncology, Royal Perth Hospital, WA.
E. Bayliss Medical Oncologist, Department of Medical Oncology, Royal Perth Hospital, WA.
J. Trotter Medical Oncologist, Department of Medical Oncology, Royal Perth Hospital, WA.
Abstract: Involvement of the thyroid gland by plasma cell neoplasms is a rare occurrence. Two modes of presentation are described; firstly as part of disseminated myeloma and secondly, as an isolated plasma cell neoplasm of the thyroid as the only evidence of disease. We wish to describe two cases of thyroid involvement as part of disseminated disease. (Aust NZ J Med 1992; 22: 139-141.) Key words: Multiple myeloma, thyroid, plasma cell neoplasm.
CASE REPORTS Case One A 70-year-old retired farmer presented in June, 1989 with a six month history of progressive hoarseness. Three months previously a fall at work resulted in mid to low thoracic back pain. The pain became worse. He also complained of 2 kg weight loss, cold intolerance and general fatigue. He had a past history of urinary tract infection with septicaemia. He was taking no medication. He admitted to two episodes of streaky haemoptysis in June and January of 1989. Examination revealed a hard, bilaterally enlarged thyroid gland with no associated lymphadenopathy. He was tender to percussion over his left ribs. The remainder of the physical examination was normal. A skeletal survey showed lytic lesions above the left mastoid, in the 5th, 6th and 7th ribs, in multiple thoracic vertebrae, in neck and shafi of the left femur and a large deposit in the left acetabulum. A thoracic C T scan demonstrated multiple expansile deposits in the ribs and vertebrae and a soft tissue mass at the left of T 4 with spinal canal encroachment. Biochemical testing showed normal urea and electrolytes and liver calcium function tests. Uric acid 0.3 mmol/L (0.18-0.49 mmol), 2.43 mmol/L (2.25-2.65 mmollL). His thyroid function tests were T 4 83 nmol/L (70-140 nmolL), TSH 1.1 m U L (0.5-6.0 mU/L). A quantitative electrophoresis showed his alpha-1 globulin to be 3 g/L, alpha-2 globulin 8 g/L, beta globulin 10 glL, gamma globulin 2 g/L (a paraprotein band was detected at 29 g/L. IEP proved this to be IgG kappa.) Immunoglobulin concentrations were IgG 0.4 g/’L (6-14.3 gL), IgA 0.9 g/L (0.65-3.4). Bence Jones protein was detected but not quantitated. Full blood count showed the haemoglobin to be 155 g/L, the white cell count 6.4 x 10p/L, platelets 340 x 109/Land ESR 35 mm per hour.
Fine needle aspirates from both lobes of the thyroid and one from the ribs demonstrated large numbers of malignant plasma cells. The nuclei were centrally placed with coarsely granular chromatin and nucleoli. The cytoplasm was amphophilic and at times granular. The changes were felt to be consistent with multiple myeloma. Under dexamethasone cover, the patient received radiotherapy to his thoracic spine resulting in resolution of the back pain. Subsequently he was started on three weekly courses of cyclophosphamide 150 mg daily for five days in association with prednisolone 100 mg daily. His thyroid rapidly shrank and was no longer palpable. He has remained well without recurrence of bone pain or thyroid enlargement. The paraprotein hand fell to a low of 12 g/L after several cycles of therapy, but in July 1991 was again measured at 29 g/L. He has not had any recent Bence Jones protein estimations. Case Two A 65-year-old man was referred in July, 1985 to the Combined Head and Neck Clinic with a blocked nose. He was found to have an ethmoid mass. Intra-nasal antrostomy and partial ethmoid clearance were performed with histological examination revealing a plasmacytoma. He received radiotherapy to the atfected ethmoid sinus because of C T evidence of residual disease in the antrum and ethmoid. There was no intracranial disease. Bence Jones protein, quantitative electrophoresis, specific X-rays of his ribs and bone marrow examination showed no evidence of disease elsewhere. In February, 1987 he presented with a mass which was fured to his left mandible just anterior to the ramus. Fine needle cytology and operative biopsy confirmed a plasmacytoma. Further investigations showed no evidence of diffise disease apart from possible deposits in the left 9th and 10th ribs.
Reprinz requests lo: Dr R. Patel, Department of Nuclear Medicine, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia. *Current address: Department of Nuclear Medicine, Royal Prince Alfred Hospital, Sydney, NSW. THYROID DISEASE IN MYELOMA
Aust NZ J Med 1992; 22
139
TABLE 1 Reported cases of Thyroid Involvement by Plasma Cell Neoplasm Period Period between followed myeloma DX after thyroid to thyroid & involvement outcome
Tre:Az?j for
Case No Authors
Age' Sex
1 Voegt 2 Shaw & Smith 3 Hazard & Schildecker
? 50 F
0 0
?
54 M
0
16v DOC
(recurrence 10 yrs later) Lt TX, FIT 3750 r
4 Hazard & Shildecker 5 Barton & Farmer 6 Castlemar 7 Willis 8 Guerrier et a/, 9 More et a/, 10 More et a/.
71 M 77 F 62 M 64 F 54 F 51 F 44 F
0
5YA 3 y 4
i t TX, RT 1700 r
11 More et a/ 12 Oberkircher et a/ 13 Sasse et a/. 14 Shirnaoka et a/. * 15 Shimoaka et a/. * 16 Shirnaoka et a/.' 17 Shimoaka et a/. *
50 M 82 F 70 M 58 F 69 M 62 M 66 M
0
3Y 2rn 0
0 0
0
0 0 2y 3y 7y 0
7
DOD 10 m A I Y A 3YA
4yDOD 4 y DOC 10 d DOC 3 m A 5 m DOD 7 y DOD 8YA
Bone Bone Bence Parapro- Antithyroid Remarks lesion marrow Jones teinernia Antibodies
-
-
TX, RT
TX TX
TX TX, T4 TX (recurrence 1 yr later) RT on T4 RTonDT radioiodine TX,R 2300 r RT2600 r Lt TX, RT
-
+ +
-
-
-
-
+
+
-
+ + + -
+ + + + -
+ -
-
-
+ -
-
-
+ + + + + -
-
Ca breast
-
-
Cacecum
m-months,y-years;A-alive at the time of the report; DOD-diedof disease; DOC-diedof other cause, TX-thyroidectomv;RT-radiationtherapy; T4-thvroxine, DT-dexiccatedthyroid *Modified from Shimoaka et a / , Cancer Vol 41 March 1978, 1140 6
Radiotherapy was administered to the mandibular lesion, but later that year the patient developed a further deposit in the right maxilla. He received chemotherapy with cyclophosphamide and prednisolone which produced an incomplete response. In October, 1987 his disease had progressed with involvement of the right antrum as well as multiple skeletal lesions. He required irradiation to the right antrum and a number of painful bony sites. Quantitative immunoglobulin estimation revealed normal IgG and IgM. The IgA was measured at 7.8 glL (0.65-3.4). Immunoelectrophoresis revealed two low concentration abnormal bands in the gamma region containing monoclonal IgA lambda. A large right femoral deposit required prophylactic internal fixation. In February, 1988 a mass at the right side of the neck became apparent over 24 hours with examination revealing a hard 4.3 cm nontender mass in the right lobe of the thyroid. Fine needle aspiration revealed plasmacytoid cells resembling those seen in previous biopsies and consistent with multiple myeloma in the thyroid. A technetium - 99m scan of the thyroid showed poor delineation of the thyroid presumably due to a blocking agent with 0.3% of the administered dose being taken up at 26 minutes post injection. A non-functioning area corresponded to the palpable thyroid nodule. No thyroid function tests were done, although the patient was clinically euthyroid. He was treated with Melphalan and prednisolone. His myeloma in general and the thyroid nodule in particular failed to respond and he required external beam radiotherapy to the thyroid mass, receiving 16 Gray in eight fractions over 15 days, and resulting in shrinkage of the thyroid mass. He continued to deteriorate however and died in June, 1988.
DISCUSSION Involvement of the thyroid gland by plasma cell neoplasms
140
is rare. A search of the available literature could find only 17 cases of thyroid gland involvement and the nature of this involvement varied considerably from case to case. In some cases the development of thyroid disease was a new manifestation in the setting of well established widespread myeloma. In other cases the thyroid gland appeared clinically normal during life, but autopsy examination revealed areas of disease. In yet other cases, the thyroid was the site for a primary extra medullary plasma cell neoplasm with or without adjacent lymph node metastases, but without evidence of systemic disease. Both of the cases discussed in the current report demonstrated myelomatous involvement of the thyroid preceded by widely disseminated disease elsewhere. Four cases of plasma cell involvement of the thyroid were reported by Shimaoka et al. They covered all the different modes of presentation mentioned above. They described the plasma cell tumours in their patients to be radiosensitive and that only modest doses of radiation were required for good control. In our report, one of our patients did not require radiation as he developed a local complete response to chemotherapy, although the other was refractory to cytotoxics and required irradiation which resulted in tumour response. The overall number of cases in the literature is too small to indicate whether the presence of thyroid involvement has any prognostic significance. The differential diagnosis in such cases would include lymphoma with plasmacytoid differentiation. However, this is a rare finding with few case reports in the literature.
Aust NZ J Med 1,992; 22
PATEL ET AL.
The usual therapeutic approach in patients presenting with apparently solitary plasmacytoma is to treat the lesion locally with irradiation and. then to wait and watch until the disease occurs elsewhere. If the radiotherapy is not successful in obliterating the lesion chemotherapy is used. Our case reports would seem to indicate, however, that it is reasonable to assess the local effect of systemic therapy before resorting to local radiotherapy.
I
Date of submission: 17 October 1990
References 1. Shimaoka K, Gailani S, Tsukada Y, Barcos M. Plasma cell neoplasm involving the thyroid. Cancer 1976; 41: 1140-6. 2. Hayes DW, Bennett WA, Heck FJ. Extramedullary lesions in multiple myeloma. Arch Pathol 1952; 53: 262-78. 3. Craie: I. Plasmacytoma of the thyroid. J Clin Pathol 1968; 21: 661-7.
Corrigendum munuciunai large granurar iympnucyre pruilrerariun in
DLC
wim
HTLV-I seroreactivity Y. Marlton, K. I aylor, J. McLormacK Mater Misericordiae Hospitals, Brisbane, Qld.
3.
Elliott
Queensland University of Technology, Brisbane, Qld.
Abstract: A 60-year-oldpart Aboriginal woman was observed to develop severe neutropenia and a large granular lymphocyte (LGL) proliferation five years after the diagnosis of s stemic lupus erythematosus (SLE). Monoclonality of the CD3 + ,CD4 - ,CD8 LGL population was conirmed using the novel approach of X-linked restriction fragment length polymorphism (RFLP) analysis. Indeterminate HTLV-I serology was present. The patient responded to steroid therapy. LGL proliferation in the setting of SLE and the use of X-linked RFLP analysis to define LGL clonality have not previously been reported. (Aust NZ J Med 1992; 22: 54-55.)
+
Key words: Large granular lymphocyte, SLE, HTLV-I, X-linked clonal analysis.
Figure 1 pertaining to the above article and published in Aust NZ J Med 1992; 22: 54-5 was published with the omission of the half tone plate. It is now reproduced below.
Figure 1: X-linked analysis with the HPRT gene probe showing heterozygosity for BamHl (lane 1+ 3). With HpaII digestion, the LGL are shown to be monoclonal (lane 2) and control tissue polyclonal (lane 4).
Aust NZ J Med 1992; 22
141
