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Calcified pulmonary metastases from medullary carcinoma of the thyroid
Computerized Medical Imaging and Graphics, Vol. 19, No. 4, pp. 325-328, 1995 Copyright 0 1995 Eleevier ScienceLtd Printed in the USA. All rights reserved 0895-6111/95 $9.50 + .oa
Pergamon
0895-6111(95)ooo13-5
CALCIFIED
PULMONARY METASTASES FROM CARCINOMA OF THE THYROID
MEDULLARY
James M. Jimenez,*T Sean 0. Casey,* Marc Citron,1 and Arfa Khan* Departments of *Radiology and SOncology, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, 270-05 76th Ave, New Hyde Park, NY 11042, USA (Received
1 November
1994)
Abstract-A caseof calcified pulmonarymetastases from medullary carcinomaof the thyroid is reported. This uncommoncauseof multiplecalcifiedpulmonarynodulesis demonstrated on a computerizedtomography(CT) scan andproven by pathology. Key
Words:
Thyroid medullary carcinoma, Calcified pulmonary nodules, Computed tomography (CT)
syndrome. Destruction of the body of the left clavicle, diffuse swelling of the left breast and arm, and multiple calcified liver lesions were also present [Figs 1, 2(A) and (B)]. The patient had a 20-yr history of medullary carcinoma of the thyroid diagnosed at age 22 when she presented with an asymptomatic neck mass. A total thyroidectomy with a right modified neck dissection was subsequently performed and eight of nine lymph nodes of the right neck were positive for tumor. In the two years following the diagnosis, a left radical neck dissection was performed to remove enlarging lymph nodes which were positive for metastatic disease. Chest radiographs and bone scans at that time, and as late as five years after diagnosis, remained negative. The patient was lost to follow-up at our institution. Between the ages of 29 and 35, the patient sought medical care at various facilities, during which time she had several excisions for pathologically proven metastatic nodules to her chest wall. Treatment with Adriamycin over the course of a year was instituted as well. Despite therapeutic measures, the patient became increasingly short of breath on exertion and subsequently underwent an open lung biopsy approximately 10 yrs after initial diagnosis. This biopsy was performed approximately 10 yrs prior to the current presentation. Microscopic studies revealed the presence of metastatic medullary carcinoma of the thyroid with focal stromal calcification in the tumor nodules. Radiographic studies performed at that time are not available. Calcitonin levels increased as time progressed and metastatic nodules continually recurred subcutaneously in the upper chest wall until her most recent presentation.
INTRODUCTION
Calcification of pulmonary metastatic lesions is rare and almost invariably indicates that the primary neoplasm is osteogenic sarcoma, chondrosarcoma, or synovial sarcoma (1). Papillary and mutinous adenocarcinomas are the most likely histological types of carcinoma to develop calcified lung metastases (2). Medullary carcinoma of the thyroid is not classically associated with calcified pulmonary metastatic disease. To our knowledge, there is only one reported case of calcified pulmonary metastases from medullary carcinoma of the thyroid (2). In our report, we present the first case of calcified lung metastases from medullary carcinoma of the thyroid evaluated by CT scan and proven by pathology. CASE REPORT
The patient was a 42-yr-old female who presented to our institution for management of metastatic medullary carcinoma of the thyroid. She complained of pain upon the movement of her left shoulder and swelling of the lateral portion of her left clavicle for a two-year duration. Radiation therapy elsewhere was minimally palliative and she arrived at our facility for further therapeutic options. Chest radiograph and CT scan of the chest demonstrated multiple bilateral pulmonary nodules, many of which were calcified, the largest being up to 8 mm in diameter. There was bulky mediastinal adenopathy with calcification resulting in superior vena cava tcorrespondence should be addressed to James M. Jimenez, M.D., Dept of Radiology, Long Island Jewish Medical Center, 270-05 76th Ave, New Hyde Park, NY 11042, USA. Tel.: 718-4707175; Fax: 718-343-7463. 325
326
Computerized
Medical
Imaging
and Graphics
JulyyAugust/l995,
Volume
19, Number
4
Fig. 1. Posterior-anterior chest radiograph. Multiple small high density pulmonary nodules are scattered diffusely throughout both lung fields. Soft tissue swelling of the left breast and upper arm are also noted. DISCUSSION
Medullary thyroid carcinoma is an uncommon malignant lesion of the thyroid gland and constitutes 5-10% of all thyroid malignant lesions (3). It is a solid tumor originating in the parafollicular or Ccells within the thyroid gland. The cancer may progress slowly despite an aggressive histologic appearance, and prolonged survival may be seen in patients with known metastatic disease (4). Unlike papillary carcinoma, medullary carcinoma of the thyroid has not been associated with calcified pulmonary metastases. A single case report alludes to a possible relationship between the two; however, pathologic confirmation was never obtained (2). In our case, both a chest radiograph and a CT of the chest demonstrated multiple calcified nodules in a patient with known medullary thyroid carcinoma metastatic to the lung as demonstrated by open lung biopsy. When contemplating the differential diagnosis of diffuse or multiple calcified pulmonary nodules, consideration of infectious etiology often predominates. Tuberculosis, histoplasmosis and varicella are among the infections which may present in this manner. Other etiologies to consider include hypercalcemic conditions such as chronic renal failure and multiple myeloma, silicosis, chronic pulmonary
venous hypertension, alveolar microlithiasis, and lymphoma following radiotherapy. These conditions often have other distinguishing features to suggest the correct
diagnosis.
Calcified
metastatic
disease is
seen most commonly with osteosarcoma, chondrosarcoma, and synovial sarcoma (1). Mutinous adenocarcinoma of the colon or breast, thyroid papillary carcinoma, ovarian cystadenocarcinoma, and carcinoid tases (5).
tumor
may also have calcified metas-
The typical appearance of medullary carcinoma lung metastases has been described as multiple nodular lesions of similar size, predominantly in the middle and lower lung field (6). The case we have described follows this description with an additional finding of nodular calcification. The multiple calcified pulmonary nodules on our patient’s chest radiograph and chest CT resembled granulomas. The patient additionally demonstrated calcified lymph nodes in the neck and mediastinum as well as calcified liver lesions. With such a presentation, miliary histoplasmosis or tuberculosis should be considered; however, there were no splenic calcifications as would be expected. Neck and nodal calcifications from medullary carcinoma of the thyroid have previously been described (6). The mechanisms of calcification in pulmonary metastases are variable and depend on the nature of
Thyroid carcinoma metastases J. M. l
JIMENEZ
et al.
327
(B
Fig. 2(A) and (B). The CT scan. Lung and mediastinal windows demonstrate numerous, up to 8 mm, calcific pulmonary nodules present bilaterally. Bulky mediastinal adenopathy with calcification is seen. Soft tissue swelling about the chest wall is also apparent.
the primary neoplasm. The best known mechanism is ossification as seen in sarcomas. In metastases of mutinous adenocarcinomas, mucinoid calcification occurs in the mucus products (7). In our case, the calcification is likely dystrophic, secondary to two
possible mechanisms. Psammoma body form .ation with resulting calcification as well as simple dystrophic calcification have been previously described in neck calcifications in medullary carcinoma (If the thyroid (8). Metastases with psammomatous calcifi-
328
Computerized Medical Imaging and Graphics
cation have also been described in other carcinomas such as papillary carcinoma of the thyroid (6). Radiographically, these calcifications usually have a fine granular appearance on chest radiographs, such as in our case. The other possible mechanism of dystrophic calcification in the lung metastases in the present case may be from degeneration and necrosis following chemotherapy. Such a mechanism has been reported in gestational trophoblastic lung metastases (9) as well as metastatic disease from prostatic carcinoma (10). Our patient received a course of Adriamycin approximately four years prior to an open lung biopsy. The causes of calcification by either method are likely increased by the extended survival of our patient, unusual in other metastastic cancers. Pulmonary metastases in the present case were present for at least 11 yrs. In conclusion, the case described in this report a relationship between calcified demonstrates p,ulmonary metastastic disease and medullary carcinoma of the thyroid. Chest radiograph and chest CT in conjunction with an open lung biopsy effectively confirm such an association. SUMMARY This case report describes the first case of calcified lung metastases from medullary carcinoma of the thyroid evaluated by CT scan and proven by pathology. The patient is a 42-yr-old female, with a 20-yr history of medullary carcinoma of the thyroid, found to have bilateral calcified pulmonary metastases. Unlike papillary carcinoma, a relationship between medullary carcinoma of the thyroid and calcified pulmonary metastases has not been clearly established. The combination of a chest radiograph, CT scan, and pathology from an open lung biopsy, effectively confirm such as association in the aforementioned case. REFERENCES 1. Zoilkofer, C.; Castaneda-Zuniga, W.; Stenlund, R.; Sibley, R. Lung metastases from synovial sarcoma simulating granulomas. AJR 135:161; 1980. 2. Maile, C.W.; Rodan, B.A.; Godwin, J.D.; Chen, J.T.T.; Ravin, C.E. Calcification in pulmonary metastases. Br. J. Radiol. 55:108-113; 1982.
July-August/l995,
Volume 19, Number 4
3. Gharib, H.; McConahey, W.M.; Tiegs, R.D.; Bergstralh, E.J.; Goellner, J.R.; Grant, C.S.; van fieerden, J.A.; Sizemore, G.W.: Hav. I.D. Meduallarv thvroid carcinoma: clinicouathologic feat&es and long te& follow-up of 65 patients ireated during 1946 through 1970. Mayo Clin. Proc. 67:934-940; 1992. 4. Schimke, R.N. Harrison’s principles of internal medicine. NY: McGraw-Hill; 1990. 5. Chapman, S.; Nakielny, R. Aids to radiological differential diagnosis. London: Bailliere Tindall; 1990. 6. Wallace, S.; Hill, C.S.; Paulus, D.D.; Ibanez, M.L.; Clark, R.L. The radiologic aspects of medullary (solid) thyroid carcinoma. Radiol. Clin. North America 8:463%447; 1970. 7. Felson, B. Chest roentgenology. PA: W.B. Saunders; 1973. 8. Editorial: Radiological aspects of familial medullary carcinoma of the thyroid. Br. Med. J. iv:569-570; 1973. 9. Cockshott, W.P.; Hendrickse, J.P. Pulmonary calcification at the site of trophoblastic metastases. Br. J. Radiol. 43:17-20; 1969. 10. Panella, J.; Mintzer, R.A. Multiple calcified pulmonary nodules in an elderly man. JAMA 244:255%2560; 1980.
About the Author-JAMEs M. JIMENEZ graduated from Bucknell University with a B.S. in Biology in 1988. He received an M.D. from New York Medical College in 1992 and was inducted into the Alpha Omega Alpha Medical Honor Society. He completed a transitional internship at New Rochelle Hospital Medical Center in 1993 and is currently a second year Diagnostic Radiology Resident at Long Island Jewish Medical Center of the Albert Einstein College of Medicine. About the Author-SEAN 0. CASEY graduated from the Johns Hopkins University with a B.A. in Natural Sciences in 1986. He attended the Albert Einstein College of Medicine, graduating with an M.D. in 1990. He served an internship in internal Medicine at North Shore University Hospital of Cornell University in 1991. He is presently a fourth year Diagnostic Radiology Resident at Long Island Jewish Medical Center of the Albert Einstein College of Medicine. Following completion of his residency in 1995, Dr Casey will begin a fellowship in Neuroradiology at the University of Colorado Health Sciences Center in Denver. About the Author-MARC CITRON graduated from Wayne State University School of Medicine in 1974. He completed a Medical residency, Chief Medical residency, and a fellowship in Medical Oncology at Georgetown University Medical Center. He is now Head, Section of Medical Oncology, at Long Island Jewish Medical Center and Associate Professor of Medicine at the Albert Einstein College of Medicine. About the Author-ARFA KHAN graduated from Medical College, Kashmir, in 1964. She then completed a Radiology residency at the Queens Hospital Center in 1970. Presently, Dr Khan is Associate Chairperson and Chief of the Division of Thoracic Radiology at L&g Island Jewish Medical Center and Professor of Radiology at the Albert Einstein College of Medicine.
Pergamon
0895-6111(95)ooo13-5
CALCIFIED
PULMONARY METASTASES FROM CARCINOMA OF THE THYROID
MEDULLARY
James M. Jimenez,*T Sean 0. Casey,* Marc Citron,1 and Arfa Khan* Departments of *Radiology and SOncology, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, 270-05 76th Ave, New Hyde Park, NY 11042, USA (Received
1 November
1994)
Abstract-A caseof calcified pulmonarymetastases from medullary carcinomaof the thyroid is reported. This uncommoncauseof multiplecalcifiedpulmonarynodulesis demonstrated on a computerizedtomography(CT) scan andproven by pathology. Key
Words:
Thyroid medullary carcinoma, Calcified pulmonary nodules, Computed tomography (CT)
syndrome. Destruction of the body of the left clavicle, diffuse swelling of the left breast and arm, and multiple calcified liver lesions were also present [Figs 1, 2(A) and (B)]. The patient had a 20-yr history of medullary carcinoma of the thyroid diagnosed at age 22 when she presented with an asymptomatic neck mass. A total thyroidectomy with a right modified neck dissection was subsequently performed and eight of nine lymph nodes of the right neck were positive for tumor. In the two years following the diagnosis, a left radical neck dissection was performed to remove enlarging lymph nodes which were positive for metastatic disease. Chest radiographs and bone scans at that time, and as late as five years after diagnosis, remained negative. The patient was lost to follow-up at our institution. Between the ages of 29 and 35, the patient sought medical care at various facilities, during which time she had several excisions for pathologically proven metastatic nodules to her chest wall. Treatment with Adriamycin over the course of a year was instituted as well. Despite therapeutic measures, the patient became increasingly short of breath on exertion and subsequently underwent an open lung biopsy approximately 10 yrs after initial diagnosis. This biopsy was performed approximately 10 yrs prior to the current presentation. Microscopic studies revealed the presence of metastatic medullary carcinoma of the thyroid with focal stromal calcification in the tumor nodules. Radiographic studies performed at that time are not available. Calcitonin levels increased as time progressed and metastatic nodules continually recurred subcutaneously in the upper chest wall until her most recent presentation.
INTRODUCTION
Calcification of pulmonary metastatic lesions is rare and almost invariably indicates that the primary neoplasm is osteogenic sarcoma, chondrosarcoma, or synovial sarcoma (1). Papillary and mutinous adenocarcinomas are the most likely histological types of carcinoma to develop calcified lung metastases (2). Medullary carcinoma of the thyroid is not classically associated with calcified pulmonary metastatic disease. To our knowledge, there is only one reported case of calcified pulmonary metastases from medullary carcinoma of the thyroid (2). In our report, we present the first case of calcified lung metastases from medullary carcinoma of the thyroid evaluated by CT scan and proven by pathology. CASE REPORT
The patient was a 42-yr-old female who presented to our institution for management of metastatic medullary carcinoma of the thyroid. She complained of pain upon the movement of her left shoulder and swelling of the lateral portion of her left clavicle for a two-year duration. Radiation therapy elsewhere was minimally palliative and she arrived at our facility for further therapeutic options. Chest radiograph and CT scan of the chest demonstrated multiple bilateral pulmonary nodules, many of which were calcified, the largest being up to 8 mm in diameter. There was bulky mediastinal adenopathy with calcification resulting in superior vena cava tcorrespondence should be addressed to James M. Jimenez, M.D., Dept of Radiology, Long Island Jewish Medical Center, 270-05 76th Ave, New Hyde Park, NY 11042, USA. Tel.: 718-4707175; Fax: 718-343-7463. 325
326
Computerized
Medical
Imaging
and Graphics
JulyyAugust/l995,
Volume
19, Number
4
Fig. 1. Posterior-anterior chest radiograph. Multiple small high density pulmonary nodules are scattered diffusely throughout both lung fields. Soft tissue swelling of the left breast and upper arm are also noted. DISCUSSION
Medullary thyroid carcinoma is an uncommon malignant lesion of the thyroid gland and constitutes 5-10% of all thyroid malignant lesions (3). It is a solid tumor originating in the parafollicular or Ccells within the thyroid gland. The cancer may progress slowly despite an aggressive histologic appearance, and prolonged survival may be seen in patients with known metastatic disease (4). Unlike papillary carcinoma, medullary carcinoma of the thyroid has not been associated with calcified pulmonary metastases. A single case report alludes to a possible relationship between the two; however, pathologic confirmation was never obtained (2). In our case, both a chest radiograph and a CT of the chest demonstrated multiple calcified nodules in a patient with known medullary thyroid carcinoma metastatic to the lung as demonstrated by open lung biopsy. When contemplating the differential diagnosis of diffuse or multiple calcified pulmonary nodules, consideration of infectious etiology often predominates. Tuberculosis, histoplasmosis and varicella are among the infections which may present in this manner. Other etiologies to consider include hypercalcemic conditions such as chronic renal failure and multiple myeloma, silicosis, chronic pulmonary
venous hypertension, alveolar microlithiasis, and lymphoma following radiotherapy. These conditions often have other distinguishing features to suggest the correct
diagnosis.
Calcified
metastatic
disease is
seen most commonly with osteosarcoma, chondrosarcoma, and synovial sarcoma (1). Mutinous adenocarcinoma of the colon or breast, thyroid papillary carcinoma, ovarian cystadenocarcinoma, and carcinoid tases (5).
tumor
may also have calcified metas-
The typical appearance of medullary carcinoma lung metastases has been described as multiple nodular lesions of similar size, predominantly in the middle and lower lung field (6). The case we have described follows this description with an additional finding of nodular calcification. The multiple calcified pulmonary nodules on our patient’s chest radiograph and chest CT resembled granulomas. The patient additionally demonstrated calcified lymph nodes in the neck and mediastinum as well as calcified liver lesions. With such a presentation, miliary histoplasmosis or tuberculosis should be considered; however, there were no splenic calcifications as would be expected. Neck and nodal calcifications from medullary carcinoma of the thyroid have previously been described (6). The mechanisms of calcification in pulmonary metastases are variable and depend on the nature of
Thyroid carcinoma metastases J. M. l
JIMENEZ
et al.
327
(B
Fig. 2(A) and (B). The CT scan. Lung and mediastinal windows demonstrate numerous, up to 8 mm, calcific pulmonary nodules present bilaterally. Bulky mediastinal adenopathy with calcification is seen. Soft tissue swelling about the chest wall is also apparent.
the primary neoplasm. The best known mechanism is ossification as seen in sarcomas. In metastases of mutinous adenocarcinomas, mucinoid calcification occurs in the mucus products (7). In our case, the calcification is likely dystrophic, secondary to two
possible mechanisms. Psammoma body form .ation with resulting calcification as well as simple dystrophic calcification have been previously described in neck calcifications in medullary carcinoma (If the thyroid (8). Metastases with psammomatous calcifi-
328
Computerized Medical Imaging and Graphics
cation have also been described in other carcinomas such as papillary carcinoma of the thyroid (6). Radiographically, these calcifications usually have a fine granular appearance on chest radiographs, such as in our case. The other possible mechanism of dystrophic calcification in the lung metastases in the present case may be from degeneration and necrosis following chemotherapy. Such a mechanism has been reported in gestational trophoblastic lung metastases (9) as well as metastatic disease from prostatic carcinoma (10). Our patient received a course of Adriamycin approximately four years prior to an open lung biopsy. The causes of calcification by either method are likely increased by the extended survival of our patient, unusual in other metastastic cancers. Pulmonary metastases in the present case were present for at least 11 yrs. In conclusion, the case described in this report a relationship between calcified demonstrates p,ulmonary metastastic disease and medullary carcinoma of the thyroid. Chest radiograph and chest CT in conjunction with an open lung biopsy effectively confirm such an association. SUMMARY This case report describes the first case of calcified lung metastases from medullary carcinoma of the thyroid evaluated by CT scan and proven by pathology. The patient is a 42-yr-old female, with a 20-yr history of medullary carcinoma of the thyroid, found to have bilateral calcified pulmonary metastases. Unlike papillary carcinoma, a relationship between medullary carcinoma of the thyroid and calcified pulmonary metastases has not been clearly established. The combination of a chest radiograph, CT scan, and pathology from an open lung biopsy, effectively confirm such as association in the aforementioned case. REFERENCES 1. Zoilkofer, C.; Castaneda-Zuniga, W.; Stenlund, R.; Sibley, R. Lung metastases from synovial sarcoma simulating granulomas. AJR 135:161; 1980. 2. Maile, C.W.; Rodan, B.A.; Godwin, J.D.; Chen, J.T.T.; Ravin, C.E. Calcification in pulmonary metastases. Br. J. Radiol. 55:108-113; 1982.
July-August/l995,
Volume 19, Number 4
3. Gharib, H.; McConahey, W.M.; Tiegs, R.D.; Bergstralh, E.J.; Goellner, J.R.; Grant, C.S.; van fieerden, J.A.; Sizemore, G.W.: Hav. I.D. Meduallarv thvroid carcinoma: clinicouathologic feat&es and long te& follow-up of 65 patients ireated during 1946 through 1970. Mayo Clin. Proc. 67:934-940; 1992. 4. Schimke, R.N. Harrison’s principles of internal medicine. NY: McGraw-Hill; 1990. 5. Chapman, S.; Nakielny, R. Aids to radiological differential diagnosis. London: Bailliere Tindall; 1990. 6. Wallace, S.; Hill, C.S.; Paulus, D.D.; Ibanez, M.L.; Clark, R.L. The radiologic aspects of medullary (solid) thyroid carcinoma. Radiol. Clin. North America 8:463%447; 1970. 7. Felson, B. Chest roentgenology. PA: W.B. Saunders; 1973. 8. Editorial: Radiological aspects of familial medullary carcinoma of the thyroid. Br. Med. J. iv:569-570; 1973. 9. Cockshott, W.P.; Hendrickse, J.P. Pulmonary calcification at the site of trophoblastic metastases. Br. J. Radiol. 43:17-20; 1969. 10. Panella, J.; Mintzer, R.A. Multiple calcified pulmonary nodules in an elderly man. JAMA 244:255%2560; 1980.
About the Author-JAMEs M. JIMENEZ graduated from Bucknell University with a B.S. in Biology in 1988. He received an M.D. from New York Medical College in 1992 and was inducted into the Alpha Omega Alpha Medical Honor Society. He completed a transitional internship at New Rochelle Hospital Medical Center in 1993 and is currently a second year Diagnostic Radiology Resident at Long Island Jewish Medical Center of the Albert Einstein College of Medicine. About the Author-SEAN 0. CASEY graduated from the Johns Hopkins University with a B.A. in Natural Sciences in 1986. He attended the Albert Einstein College of Medicine, graduating with an M.D. in 1990. He served an internship in internal Medicine at North Shore University Hospital of Cornell University in 1991. He is presently a fourth year Diagnostic Radiology Resident at Long Island Jewish Medical Center of the Albert Einstein College of Medicine. Following completion of his residency in 1995, Dr Casey will begin a fellowship in Neuroradiology at the University of Colorado Health Sciences Center in Denver. About the Author-MARC CITRON graduated from Wayne State University School of Medicine in 1974. He completed a Medical residency, Chief Medical residency, and a fellowship in Medical Oncology at Georgetown University Medical Center. He is now Head, Section of Medical Oncology, at Long Island Jewish Medical Center and Associate Professor of Medicine at the Albert Einstein College of Medicine. About the Author-ARFA KHAN graduated from Medical College, Kashmir, in 1964. She then completed a Radiology residency at the Queens Hospital Center in 1970. Presently, Dr Khan is Associate Chairperson and Chief of the Division of Thoracic Radiology at L&g Island Jewish Medical Center and Professor of Radiology at the Albert Einstein College of Medicine.