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Unusual manifestations of soft tissue metastasis
Journal of Clinical Imaging 27 (2003) 52 – 54
Unusual manifestations of soft tissue metastasis Hsueh-Chieh Lua, Tiffany Ting-Fang Shiha,b,*, Chao-Yu Hsua, Mu-Zon Wuc, Yiu-Wah Lia,b a
Department of Medical Imaging, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan b Department of Radiology, College of Medicine, National Taiwan University, Taipei, Taiwan c Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan Received 15 February 2002
Abstract We present a patient with pulmonary adenocarcinoma metastatic to the left forearm. The magnetic resonance imaging (MRI) revealed no discrete tumor, but an infiltrative signal change of the subcutaneous tissue and muscle. The lymphatic invasion by cancer cells explains this unusual manifestation of image findings. D 2002 Elsevier Science Inc. All rights reserved. Keywords: Soft tissue neoplasms; Magnetic resonance imaging; Neoplasm metastasis; Lung neoplasm; Forearm
1. Introduction Metastasis to the soft tissue is exceptionally rare [1] and difficult to be diagnosed before surgery. The magnetic resonance imaging (MRI) is able to demonstrate the soft tissue lesion and needed to clarify its findings. We present a 70-year-old man with pulmonary adenocarcinoma metastatic to the left forearm. The MRI findings show no solid mass, but only an infiltrative lesion. It is helpful to recognize the unusual manifestation of soft tissue metastasis.
2. Case report A 70-year-old male smoker was referred to our hospital due to progressive swelling of the left proximal forearm of 2 months duration. On the physical examination, there were local heat, erythema and severe tenderness at this site. The laboratory data was unremarkable. The plain radiography of left forearm revealed periosteal reaction at the distal radius and ulna. The MRI of left forearm showed diffuse infiltrative abnormal signal as a feathering-like pattern in the intermuscular and intramuscular structure, which was intermediate on T1-weighted image (TR = 570 ms, TE = 14 ms, * Corresponding author. Department of Medical Imaging, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan. Fax: +886-2-27548108. E-mail address: [email protected] (T.T.-F. Shih).
NEX 2) and high on T2-weighted image (TR = 6593 ms, TE = 112 ms, NEX 2) (Fig. 1A). After injection of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA), strong enhancement of the soft tissue as a feathering-like pattern appeared (Fig. 1B). No definite solid mass could be identified. The osseous structure was intact. On the image study of the chest including the routine plain radiography and the computed tomography scan, it showed a right perihilar mass with massive pericardial and right pleural effusion. The cytological examination of the pleural as well as pericardial effusion both showed adenocarcinoma. An excisional biopsy of the left forearm revealed nests of metastatic adenocarcinoma scattered in the desmoplastic stroma. The tumor cells presented positive on the cytokeratin stain, ethylmalonic acid stain and negative on carcinoembryonic antigen stain or prostate-specific antigen stain. In addition, aggregates of malignant cells with immature nuclei and rich cytoplasm consistent with lung adenocarcinoma was also demonstrated within the lymphatics (Fig. 1C). These findings disclosed adenocarcinoma of the lung with soft tissue metastasis.
3. Discussion It has been stated that soft tissue, especially skeletal muscle, is highly resistant to metastatic tumors in spite of its large volume, representing nearly 50% of total body mass [2,3]. In the literature, reports of such cases are uncommon.
0899-7071/03/$ – see front matter D 2002 Elsevier Science Inc. All rights reserved. PII: S 0 8 9 9 - 7 0 7 1 ( 0 2 ) 0 0 5 0 0 - 4
H.-C. Lu et al. / Journal of Clinical Imaging 27 (2003) 52–54
53
Fig. 1. T2-weighted (A) and gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA)-enhanced (B) MR images reveal infiltrative lesions of the subcutaneous tissue and muscular structure. There are diffuse feathering-like high signal on the T2-weighted image and strong enhancement after injection of Gd-DTPA, in the fascia (arrow), intermuscular and intramuscular regions (arrowheads) of the left forearm. No definite solid mass could be identified. (C) Biopsy specimen of the forearm shows malignant cells within the lymphatics (arrow). Haematoxylin-eosin stain. Original magnification 400.
Thus, an intramuscular tumor is usually first suspected to be a primary soft tissue sarcoma instead of soft tissue metastasis. Willis and Pearson reported respective frequencies of intramuscular metastases in autopsied cases ranged from 0.8% [2] to 16% [4]. Thus, it indicates that such metastases are not so rare, according to these series including both microscopic and macroscopic metastatic foci. The following explanations may be able to account for the frequency variety among the researchers. First, because of the rich blood supply, metastases frequently occur in the muscles as they do in the lung and liver, and this would correspond to the reported frequency of muscle metastases of 16% by Pearson [4]. On the other hand, the blood flow within the muscles is extremely variable and the flow turbulence may also take a part in wrecking tumor cells in the blood [5]. In addition, the development of metastases may be suppressed due to the effect of lactic acid on tumor cell production [6]. There are also kinds of proteases and other inhibitors in the soft tissue, which prohibit the enzyme-dependent steps of
tumor invasion or metastasis [1]. Cellular and humoral immunity also contribute to the low incidence of muscular metastasis [7]. Tissue oxygen tension affects the pattern of metastatic deposits as well. In a situation of high oxygen tension, such as in the skeletal muscle, toxic-free oxygen radicals tend to develop and inhibit growth of tumor cells [8]. Besides, mechanical damage to tumor cells by muscle movements may play an important role in the constraint of muscle metastasis [9]. Reviewing the previous reports, skeletal muscle metastases are found in the patients with leukemia, lymphoma, malignant melanoma, thyroid cancer, lung cancer and other neoplasms [10]. According to the study by Tanaka et al. [11], the most frequent origin was lung cancer, which accounts for half of the 28 cases of intramuscular metastasis of malignant tumors, followed by gastric cancer. Lung cancer has been known to metastasize to various organ systems. The intrathoracic involvement includes mediastinal lymph nodes, pleura, diaphragm, chest wall and
54
H.-C. Lu et al. / Journal of Clinical Imaging 27 (2003) 52–54
pericardium [12]. The most common extrathoracic metastases are the adrenal glands, bone, kidney and brain [12]. The frequency of intramuscular metastasis based on the autopsy findings by Berge and Lundberg [13] was estimated to be 1% in the 747 patients with lung cancer. The MRI findings of muscular metastasis are rarely reported and uncharacteristic. In the case report by Suto et al. [14], low signal intensity on the T1-weighted images and slightly high signal intensity on the T2-weighted images were observed in the intramuscular metastases of malignant tumors and they were usually well enhanced by Gd-DTPA. In our case, MR findings of the intramuscular metastasis were low signal intensity on the T1-weighted images, slightly high signal intensity on the T2-weighted images and well enhanced by Gd-DPTA, similar to the earlier reports. However, our case had no discrete tumor, but only an infiltrative lesion identified. An infectious process was suspected initially according to the local manifestation and its MR findings, but the pathological results demonstrate muscular metastasis. Under microscopy, infiltration of malignant tumor cells into the lymphatics was found (Fig. 1C). It indicated the possibility of lymphatic obstruction caused by tumor cell thrombus and subsequent changes of soft tissue. According to this pathologic pattern, the feathering like pattern and obvious edematous change of the soft tissue on the MRI were explained consistent with it. Due to the absence of comparative reports of metastases to the muscles and other organs, the prognosis of intramuscular metastasis is still doubtful, but most patients with such metastases expire within a few months in spite of diverse varieties of treatment [11,15]. In opposition, the prognosis of primary soft tissue sarcomas has been obviously improved by early recognition and radical surgery. Hence, it is important to differentiate the soft tissue metastasis from the primary soft tissue malignancy. To date, the MRI has already become the most important imaging tool for soft tissue lesions. This imaging modality has the advantages of excellent contrast resolution, the good ability to provide tissue characterization and the capacity for
performance of multiplanar acquisition. Availability of the MRI and heightened clinical suspicion will contribute to an accurate diagnosis of soft tissue metastasis.
References [1] Sridhar KS, Rao RK, Kunhardt B. Skeletal muscle metastases from lung cancer. Cancer 1987;59:1530 – 4. [2] Willis RA. Secondary tumours in sundry unusual situations. In: Willis RA, editor. The spread of tumors in the human body. London: Butterworths, 1973. p. 279. [3] Rubin P, Green J. Susceptibility of specific tissues for metastases. In: Rubin P, Green J, editors. Solitary metastases. Springfield: C.C. Thomas, 1968. p. 6. [4] Pearson CM. Incidence and type of pathologic alterations observed in muscle in a routine autopsy survey. Neurology 1959;9:757. [5] Inalsingh CH, Hazra T, Prempree T. Unusual metastases from carcinoma of the lung. J Can Assoc Radiol 1974;25:242 – 4. [6] Seely S. Possible reasons for the high resistance of muscle to cancer. Med Hypotheses 1980;6:133 – 7. [7] Poste G, Fidler IJ. The pathogenesis of cancer metastasis. Nature 1980;283:139 – 46. [8] Fidler IJ, Hart IR. Principles of cancer biology, biology of cancer metastasis. In: Devita VT, Hellman S, Rosenberg SA, editors. Cancer, principles and practice of oncology. Philadelphia: Lippincott, 1982. pp. 80 – 92. [9] Mulsow FW. Metastatic carcinoma of skeletal muscles. Arch Pathol 1943;35:112. [10] Rotterdam H, Salvutin L. Secondary tumors of soft tissues: an autopsy study. In: Fenoglio CM, Wolff M, editors. Progress in surgical pathology. New York: Masson, 1980. pp. 147 – 68. [11] Tanaka M, Suyama N, Masumoto H, Araki J, Asai S. A case of squamous cell carcinoma of the lung with metastasis to a limb muscle [Japanese]. Haigan 1992;32:1055 – 60. [12] Matthews MJ, Kanhouwa S, Pickren J, Robinette D. Frequency of residual and metastatic tumor in patients undergoing curative surgical resection for lung cancer. Cancer Chemother Rep 1973;4:63 – 7. [13] Berge T, Lundberg S. Cancer in Malmo 1958 – 1969. An autopsy study. Acta Pathol Suppl 1977;260:1 – 235. [14] Suto Y, Yamaguchi Y, Sugihara S. Skeletal muscle metastasis from lung carcinoma: MR findings. J Comput Assist Tomogr 1997;21: 304 – 5. [15] Rosenbaum LH, Nicholas JJ, Slasky BS, Obley DL, Ellis LD. Malignant myositis ossificans: occult gastric carcinoma presenting as an acute rheumatic disorder. Ann Rheum Dis 1984;43:95 – 7.
Unusual manifestations of soft tissue metastasis Hsueh-Chieh Lua, Tiffany Ting-Fang Shiha,b,*, Chao-Yu Hsua, Mu-Zon Wuc, Yiu-Wah Lia,b a
Department of Medical Imaging, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan b Department of Radiology, College of Medicine, National Taiwan University, Taipei, Taiwan c Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan Received 15 February 2002
Abstract We present a patient with pulmonary adenocarcinoma metastatic to the left forearm. The magnetic resonance imaging (MRI) revealed no discrete tumor, but an infiltrative signal change of the subcutaneous tissue and muscle. The lymphatic invasion by cancer cells explains this unusual manifestation of image findings. D 2002 Elsevier Science Inc. All rights reserved. Keywords: Soft tissue neoplasms; Magnetic resonance imaging; Neoplasm metastasis; Lung neoplasm; Forearm
1. Introduction Metastasis to the soft tissue is exceptionally rare [1] and difficult to be diagnosed before surgery. The magnetic resonance imaging (MRI) is able to demonstrate the soft tissue lesion and needed to clarify its findings. We present a 70-year-old man with pulmonary adenocarcinoma metastatic to the left forearm. The MRI findings show no solid mass, but only an infiltrative lesion. It is helpful to recognize the unusual manifestation of soft tissue metastasis.
2. Case report A 70-year-old male smoker was referred to our hospital due to progressive swelling of the left proximal forearm of 2 months duration. On the physical examination, there were local heat, erythema and severe tenderness at this site. The laboratory data was unremarkable. The plain radiography of left forearm revealed periosteal reaction at the distal radius and ulna. The MRI of left forearm showed diffuse infiltrative abnormal signal as a feathering-like pattern in the intermuscular and intramuscular structure, which was intermediate on T1-weighted image (TR = 570 ms, TE = 14 ms, * Corresponding author. Department of Medical Imaging, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan. Fax: +886-2-27548108. E-mail address: [email protected] (T.T.-F. Shih).
NEX 2) and high on T2-weighted image (TR = 6593 ms, TE = 112 ms, NEX 2) (Fig. 1A). After injection of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA), strong enhancement of the soft tissue as a feathering-like pattern appeared (Fig. 1B). No definite solid mass could be identified. The osseous structure was intact. On the image study of the chest including the routine plain radiography and the computed tomography scan, it showed a right perihilar mass with massive pericardial and right pleural effusion. The cytological examination of the pleural as well as pericardial effusion both showed adenocarcinoma. An excisional biopsy of the left forearm revealed nests of metastatic adenocarcinoma scattered in the desmoplastic stroma. The tumor cells presented positive on the cytokeratin stain, ethylmalonic acid stain and negative on carcinoembryonic antigen stain or prostate-specific antigen stain. In addition, aggregates of malignant cells with immature nuclei and rich cytoplasm consistent with lung adenocarcinoma was also demonstrated within the lymphatics (Fig. 1C). These findings disclosed adenocarcinoma of the lung with soft tissue metastasis.
3. Discussion It has been stated that soft tissue, especially skeletal muscle, is highly resistant to metastatic tumors in spite of its large volume, representing nearly 50% of total body mass [2,3]. In the literature, reports of such cases are uncommon.
0899-7071/03/$ – see front matter D 2002 Elsevier Science Inc. All rights reserved. PII: S 0 8 9 9 - 7 0 7 1 ( 0 2 ) 0 0 5 0 0 - 4
H.-C. Lu et al. / Journal of Clinical Imaging 27 (2003) 52–54
53
Fig. 1. T2-weighted (A) and gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA)-enhanced (B) MR images reveal infiltrative lesions of the subcutaneous tissue and muscular structure. There are diffuse feathering-like high signal on the T2-weighted image and strong enhancement after injection of Gd-DTPA, in the fascia (arrow), intermuscular and intramuscular regions (arrowheads) of the left forearm. No definite solid mass could be identified. (C) Biopsy specimen of the forearm shows malignant cells within the lymphatics (arrow). Haematoxylin-eosin stain. Original magnification 400.
Thus, an intramuscular tumor is usually first suspected to be a primary soft tissue sarcoma instead of soft tissue metastasis. Willis and Pearson reported respective frequencies of intramuscular metastases in autopsied cases ranged from 0.8% [2] to 16% [4]. Thus, it indicates that such metastases are not so rare, according to these series including both microscopic and macroscopic metastatic foci. The following explanations may be able to account for the frequency variety among the researchers. First, because of the rich blood supply, metastases frequently occur in the muscles as they do in the lung and liver, and this would correspond to the reported frequency of muscle metastases of 16% by Pearson [4]. On the other hand, the blood flow within the muscles is extremely variable and the flow turbulence may also take a part in wrecking tumor cells in the blood [5]. In addition, the development of metastases may be suppressed due to the effect of lactic acid on tumor cell production [6]. There are also kinds of proteases and other inhibitors in the soft tissue, which prohibit the enzyme-dependent steps of
tumor invasion or metastasis [1]. Cellular and humoral immunity also contribute to the low incidence of muscular metastasis [7]. Tissue oxygen tension affects the pattern of metastatic deposits as well. In a situation of high oxygen tension, such as in the skeletal muscle, toxic-free oxygen radicals tend to develop and inhibit growth of tumor cells [8]. Besides, mechanical damage to tumor cells by muscle movements may play an important role in the constraint of muscle metastasis [9]. Reviewing the previous reports, skeletal muscle metastases are found in the patients with leukemia, lymphoma, malignant melanoma, thyroid cancer, lung cancer and other neoplasms [10]. According to the study by Tanaka et al. [11], the most frequent origin was lung cancer, which accounts for half of the 28 cases of intramuscular metastasis of malignant tumors, followed by gastric cancer. Lung cancer has been known to metastasize to various organ systems. The intrathoracic involvement includes mediastinal lymph nodes, pleura, diaphragm, chest wall and
54
H.-C. Lu et al. / Journal of Clinical Imaging 27 (2003) 52–54
pericardium [12]. The most common extrathoracic metastases are the adrenal glands, bone, kidney and brain [12]. The frequency of intramuscular metastasis based on the autopsy findings by Berge and Lundberg [13] was estimated to be 1% in the 747 patients with lung cancer. The MRI findings of muscular metastasis are rarely reported and uncharacteristic. In the case report by Suto et al. [14], low signal intensity on the T1-weighted images and slightly high signal intensity on the T2-weighted images were observed in the intramuscular metastases of malignant tumors and they were usually well enhanced by Gd-DTPA. In our case, MR findings of the intramuscular metastasis were low signal intensity on the T1-weighted images, slightly high signal intensity on the T2-weighted images and well enhanced by Gd-DPTA, similar to the earlier reports. However, our case had no discrete tumor, but only an infiltrative lesion identified. An infectious process was suspected initially according to the local manifestation and its MR findings, but the pathological results demonstrate muscular metastasis. Under microscopy, infiltration of malignant tumor cells into the lymphatics was found (Fig. 1C). It indicated the possibility of lymphatic obstruction caused by tumor cell thrombus and subsequent changes of soft tissue. According to this pathologic pattern, the feathering like pattern and obvious edematous change of the soft tissue on the MRI were explained consistent with it. Due to the absence of comparative reports of metastases to the muscles and other organs, the prognosis of intramuscular metastasis is still doubtful, but most patients with such metastases expire within a few months in spite of diverse varieties of treatment [11,15]. In opposition, the prognosis of primary soft tissue sarcomas has been obviously improved by early recognition and radical surgery. Hence, it is important to differentiate the soft tissue metastasis from the primary soft tissue malignancy. To date, the MRI has already become the most important imaging tool for soft tissue lesions. This imaging modality has the advantages of excellent contrast resolution, the good ability to provide tissue characterization and the capacity for
performance of multiplanar acquisition. Availability of the MRI and heightened clinical suspicion will contribute to an accurate diagnosis of soft tissue metastasis.
References [1] Sridhar KS, Rao RK, Kunhardt B. Skeletal muscle metastases from lung cancer. Cancer 1987;59:1530 – 4. [2] Willis RA. Secondary tumours in sundry unusual situations. In: Willis RA, editor. The spread of tumors in the human body. London: Butterworths, 1973. p. 279. [3] Rubin P, Green J. Susceptibility of specific tissues for metastases. In: Rubin P, Green J, editors. Solitary metastases. Springfield: C.C. Thomas, 1968. p. 6. [4] Pearson CM. Incidence and type of pathologic alterations observed in muscle in a routine autopsy survey. Neurology 1959;9:757. [5] Inalsingh CH, Hazra T, Prempree T. Unusual metastases from carcinoma of the lung. J Can Assoc Radiol 1974;25:242 – 4. [6] Seely S. Possible reasons for the high resistance of muscle to cancer. Med Hypotheses 1980;6:133 – 7. [7] Poste G, Fidler IJ. The pathogenesis of cancer metastasis. Nature 1980;283:139 – 46. [8] Fidler IJ, Hart IR. Principles of cancer biology, biology of cancer metastasis. In: Devita VT, Hellman S, Rosenberg SA, editors. Cancer, principles and practice of oncology. Philadelphia: Lippincott, 1982. pp. 80 – 92. [9] Mulsow FW. Metastatic carcinoma of skeletal muscles. Arch Pathol 1943;35:112. [10] Rotterdam H, Salvutin L. Secondary tumors of soft tissues: an autopsy study. In: Fenoglio CM, Wolff M, editors. Progress in surgical pathology. New York: Masson, 1980. pp. 147 – 68. [11] Tanaka M, Suyama N, Masumoto H, Araki J, Asai S. A case of squamous cell carcinoma of the lung with metastasis to a limb muscle [Japanese]. Haigan 1992;32:1055 – 60. [12] Matthews MJ, Kanhouwa S, Pickren J, Robinette D. Frequency of residual and metastatic tumor in patients undergoing curative surgical resection for lung cancer. Cancer Chemother Rep 1973;4:63 – 7. [13] Berge T, Lundberg S. Cancer in Malmo 1958 – 1969. An autopsy study. Acta Pathol Suppl 1977;260:1 – 235. [14] Suto Y, Yamaguchi Y, Sugihara S. Skeletal muscle metastasis from lung carcinoma: MR findings. J Comput Assist Tomogr 1997;21: 304 – 5. [15] Rosenbaum LH, Nicholas JJ, Slasky BS, Obley DL, Ellis LD. Malignant myositis ossificans: occult gastric carcinoma presenting as an acute rheumatic disorder. Ann Rheum Dis 1984;43:95 – 7.