Clinical Imaging 38 (2014) 330–332
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
Pulmonary leiomyomas in a patient with bilateral renal cell cancer mimicking pulmonary metastases Ying-Yi Chen a, Seng-Tang Wu b, Hsian-Her Hsu c, Ya-Cheng Chen c, Shih-Chun Lee a, Hung Chang a, Tsai-Wang Huang a,⁎ a b c
Division of Thoracic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
a r t i c l e
i n f o
Article history: Received 21 October 2013 Received in revised form 10 January 2014 Accepted 15 January 2014 Keywords: Pulmonary leiomyoma Renal cell carcinoma Pulmonary metastasis
a b s t r a c t Pulmonary benign metastasizing leiomyoma (PBML) characterized by uterine leiomyoma in the lung is very rare. Here we report the case of a 55-year-old woman with a history of surgically resected multiple uterine leiomyomas who was histopathologically diagnosed with PBML associated with bilateral primary renal cell carcinoma (RCC). Clinicians should be aware of this unusual entity and consider pulmonary leiomyoma as a differential diagnosis in asymptomatic women with primary RCC and a history of hysterectomy for leiomyoma.
1. Introduction Pulmonary benign metastasizing leiomyoma (PBML) is a very rare disease characterized by the growth of uterine leiomyoma in the lungs [1]. Benign metastasizing leiomyoma (BML) was first identified by Steiner in 1939, and he believed it to be a primary pulmonary neoplasm. Therefore, BML was first referred to as fibroleiomyomatous hamartoma. Most patients present with a history of hysterectomy for uterine leiomyoma. However, the pathogenesis of this disease has not yet been elucidated. Here we report the case of a 55-year-old woman who underwent total abdominal hysterectomy for multiple uterine leiomyomas 10 years before presenting with bilateral renal cell carcinoma (RCC) and multiple shadows on a chest radiograph. These pulmonary nodules appeared to be distant metastases from the RCCs. This case report indicates that clinicians should be aware of this unusual entity and consider pulmonary leiomyoma as a differential diagnosis in an asymptomatic woman with primary RCC and a history of hysterectomy for leiomyoma. 2. Case report A 55-year-old woman presented with a 1-month history of general weakness, poor appetite, and weight loss (5 kg). She reported a ⁎ Corresponding author. Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, 325, Section 2, Cheng-Kung Road, Taipei 114, Taiwan, ROC. Tel.: +886 2 87927167; fax: +886 2 87927403. E-mail address: [email protected] (T.-W. Huang). 0899-7071/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clinimag.2014.01.008
© 2014 Elsevier Inc. All rights reserved.
history of hypertension that was being controlled with regular medication for 5 years; furthermore, she had been diagnosed with bilateral autosomal dominant polycystic disease (ADPKD) 7 years back and had undergone total abdominal hysterectomy for uterine leiomyomas accompanied by heavy and painful menstruation, painful sexual intercourse, and abnormal gynecological hemorrhage 10 years back. Physical examination revealed no rebounding tenderness over the abdomen, clear breath sounds in both lungs, and mildly pale conjunctiva. Urinalysis revealed no hematuria or pyuria. Abdominal sonography showed multiple hepatic and renal cysts and a solid nodule in each kidney. Plain chest radiography revealed bilateral, multiple, different-sized pulmonary nodules (Fig. 1). Abdominal magnetic resonance (MR) images of different sequences showed multiple, different-sized, hepatic (the largest measuring approximately 10.9 cm in the right lobe) and bilateral renal cystic lesions. In addition, a solid nodule measuring 7.8 cm and one measuring 3.1 cm were observed on the lower pole of the right kidney and in the sinus region of the left kidney, respectively (Fig. 2A–C). Sonography-guided needle biopsies were performed for both kidney nodules, which were histopathologically confirmed to be RCCs. The right and left lesions were chromophobe cell (CD10-negative; EMA-positive; vimentin, equivocal; CK7-positive) and conventional clear cell (CD10positive; EMA-positive; vimentin, positive; CK18-positive; pVHLpositive) RCCs, respectively. Bilateral, multiple pulmonary nodules and masses of different sizes (b3.6 cm) were observed with both central and peripheral distribution. Multiple, different-sized, hepatic cystic lesions were also observed on chest computed tomography (CT) (Fig. 3). A whole-body bone scan revealed no bone metastases. A CT-guided core
Y.2Y. Chen et al. / Clinical Imaging 38 (2014) 330–332
331
Fig. 1. Plain chest radiograph. The plain radiograph shows multiple scattered nodules of different sizes in both lung fields. Distribution is both central and peripheral, suggestive of pulmonary metastases.
needle biopsy was performed using an 18-gauge needle, but no definitive diagnosis was established. As a differential diagnosis, RCC with multiple pulmonary metastases was initially considered, and video-assisted thoracoscopic surgery with wedge resection of the right middle and lower lobes was performed to confirm the diagnosis and determine the treatment strategy. Postoperative histopathological examination revealed spindle-shaped cells with abundant clear cytoplasm and distinct cell borders, low mitotic activity (b 0–1/10 high power fields), little cytological cellular atypia, and no tumor cell necrosis. These pulmonary lesions were thus determined to be metastasizing leiomyomas according to the pathophysiology and immunohistochemical staining [actin-positive, CD10-negative, CK7-negative, PAX-2-negative, PAX-8-negative, vimentin-negative, CD117-negative, S-100-negative, HMB45-negative, estrogen receptor (ER)-positive; progesterone receptor (PR)-positive]. The PR and ER positivity indicated PBML. Therefore, the final diagnoses were as follows: (1) RCC, conventional type, left, stage cT1aN0M0; (2) RCC, chromophobe type, right, stage cT2aN0M0; and (3) bilateral PBML. A dynamic renal/urinary function test (99mTc-diethylenetriaminepentaacetic acid) for preoperative evaluation of differential renal function showed the following: (1) right kidney, moderately decreased blood flow and effective renal plasma flow (ERPF; 130 ml/min); (2) left kidney, moderately decreased blood flow and ERPF (123 ml/min); post-renal, marked obstruction and poor response to diuretics. The left RCC was centrally located and partially obstructed the upper urinary tract. This compromised renal function contraindicated immediate surgical resection. Therefore, a tyrosine-kinase inhibitor (TKI; pazopanib HCl) was prescribed to restore renal function, and partial nephrectomy of the right kidney was performed 3 months later. After 6 months, partial nephrectomy of the left kidney was performed under a stable condition and effective control by TKI. Regular follow-up was conducted on an outpatient basis; there was no tumor progression or recurrence for a year. 3. Discussion BML is a rare disease characterized by the appearance of relatively small pulmonary nodules several years after the removal of a histologically unremarkable uterus [2,3]. The mean duration between hysterectomy and the appearance of pulmonary lesions was report-
Fig. 2. Abdominal MR imaging. Two soft tissue masses, one measuring 3.1 cm in the parapelvic region of the left kidney (a) and one measuring 7.8 cm on the lower pole of the right kidney (b), along with enlargement of both kidneys with multiple cysts of different sizes (c), consistent with autosomal dominant polycystic disease, are observed. (A) T1-weighted coronal MR image shows mild hypointensity of the soft tissue lesions at both kidneys. (B) T2-weighted coronal MR image shows mild hyperintensity of the soft tissue lesions. (C) Contrast-enhanced T1-weighted coronal MR image shows enhancement of the soft tissue lesions over bilateral kidneys.
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Y.2Y. Chen et al. / Clinical Imaging 38 (2014) 330–332
Fig. 3. Coronal contrast-enhanced chest CT at the arterial phase of the soft tissue window. Multiple nodules and masses of different sizes (b3.6 cm) are scattered throughout both lungs, with both central and peripheral distribution (white arrow). Multiple cystic lesions of different sizes are seen in the liver, with the largest measuring approximately 10.9 cm in the right lobe (a).
edly 15 years [4]. There is no clear mechanism reported to underlie BML onset, and several different hypotheses are suggested. Some investigators have postulated that BMLs are actually low-grade leiomyosarcomas [4–6], while others consider pulmonary lesions to represent the intravascular spread of a benign uterine leiomyoma. The latter theory is similar to that for the origin of endometriosis at distant sites such as the lungs and postulates that BMLs and intravascular leiomyomatosis are related entities [7]. Diagnosing BML is very difficult, with strict pathological diagnostic criteria based on immunohistochemistry and a history of hysterectomy for uterine leiomyoma [8]. In our case, the housefield unit for the multiple pulmonary nodules on contrast-enhanced chest CT was + 30 (liver, + 50), and the pulmonary lesions were not contrast enhanced. The tumor cells were strongly positive for smooth muscle actin, confirming the smooth muscle origin. In addition, immunohistochemical staining revealed CD117 negativity, ruling out extragastrointestinal stromal tumor. All cells were S100 negative, essentially excluding a tumor of neural origin. The positive ER and PR immunoreactivity suggested that the spindle-shaped cells were uterine smooth muscle cells. Most pulmonary leiomyomas reported in the literature were associated with hereditary leiomyomatosis and RCC. Reed’s syndrome (or familial leiomyomatosis) is a rare inherited condition characterized by multiple cutaneous leiomyomas and, in women, uterine leiomyomas. This condition predisposes for RCC [9] and is also associated with an increased risk of uterine leiomyosarcoma [10]. The syndrome is caused by a mutation in the fumarate hydratase gene, which leads to fumarate accumulation. The inheritance pattern is autosomal dominant. This syndrome was ruled out for our patient because there was no family history of associated diseases and no associated skin lesions such as cutaneous leiomyomas. Except in patients with Reed’s syndrome, PBML with synchronous bilateral RCC has not been reported. Osadchy et al. [11] reported a case of PBML with left RCC. Several recent publications report notable findings on 18Ffluorodeoxyglucose positron emission tomography/CT (FDG PET-CT) [12–15]. However, another study reported that PET/CT [8] did not show abnormal FDG uptake, with an approximate standardized uptake value of 2. Also, Ogawa et al. [15] found that not all of these
pulmonary nodules comprised benign cells. FDG PET-CT could indicate a mild homogeneous and markedly elevated heterogeneous accumulation in the benign and malignant components, respectively. The heterogeneity may reflect necrosis within the tumor. Currently, there are no standard treatment guidelines for PBML. Reported modalities include careful observation, surgical resection, hysterectomy and bilateral oophorectomy, progestins, aromatase inhibitors, and medical castration with luteinizing hormone-releasing hormone analogs [16]. However, surgery combined with hormone therapy is considered optimal [17]. Renal masses of both kidneys were highly suspicious of malignancy related according to MR images before biopsy. The pulmonary nodules in our patient appeared to be distant metastases from RCC. Because CT-guided biopsy did not yield a conclusive diagnosis, surgical resection and histopathological examination allowed for precise clinical staging and appropriate management. In our patient, RCC subtype differed between both kidneys, requiring separate treatment. After achieving systemic control through targeted TKI therapy, partial nephrectomies were separately performed at a 6-month interval. In conclusion, clinicians should be aware of the possibility of this unusual entity, particularly in patients with RCC. Pulmonary leiomyoma should be considered as a differential diagnosis in an asymptomatic woman with primary RCC and a history of hysterectomy for leiomyoma. References [1] Steiner P. Metastasizing fibroleiomyoma of the uterus: report of a case and review of the literature. Am J Pathol 1939;15:89–107. [2] Abell MR, Littler ER. Benign metastasizing uterine leiomyoma. Multiple lymph nodal metastases. Cancer 1975;36:2206–13. [3] Nucci MR, Drapkin R, Cin PD, Fletcher CD, Fletcher JA. Distinctive cytogenetic profile in benign metastasizing leiomyoma: pathogenic implications. Am J Surg Pathol 2007;31:737–43. [4] Kayser K, Zink S, Schneider T, Dienemann H, André S, Kaltner H, Schüring MP, Zick Y, Gabius HJ. Benign metastasizing leiomyoma of the uterus: documentation of clinical, immunohistochemical and lectin-histochemical data of ten cases. Virchows Arch 2000;437:284–92. [5] Esteban JM, Allen WM, Schaerf RH. Benign metastasizing leiomyoma of the uterus: histologic and immunohistochemical characterization of primary and metastatic lesions. Arch Pathol Lab Med 1999;123:960–2. [6] Jautzke G, Muller-Ruchholtz E, Thalmann U. Immunohistological detection of estrogen and progesterone receptors in multiple and well differentiated leiomyomatous lung tumors in women with uterine leiomyomas. A report on 5 cases. Pathol Res Pract 1996;192:215–23. [7] Koh DM, Burn PR, King DM. Benign metastasizing leiomyoma with intracaval leiomyomatosis. Br J Radiol 2000;73:435–7. [8] Fu Y, Li H, Tian B, Hu B. Pulmonary benign metastasizing leiomyoma: a case report and review of the literature. World J Surg Oncol 2012;10:268. [9] Tolvanen J, Uimari O, Ryynänen M, Aaltonen LA, Vahteristo P. Strong family history of uterine leiomyomatosis warrants fumarate hydratase mutation screening. Hum Reprod 2012;27:1865–9. [10] Toro J, Nickerson M, Wei MH, Warren MB, Glenn GM, Turner ML, Stewart L, Duray P, Tourre O, Sharma N, Choyke P, Stratton P, Merino M, Walther MM, Linehan WM, Schimdt LS, Zbar B. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. Am J Hum Genet 2003;73:95–106. [11] Osadchy A, Zehavi T, Zissin R. Pulmonary benign metastasising leiomyomas presenting as fluid-containing masses on CT in a patient with two unrelated malignancies. Br J Radiol 2005;78:639–41. [12] Sapmaz F, Ergin M, Katrancioglu O, Gonlugur T, Gonlugur U, Elagoz S. Benign metastasizing leiomyoma. Lung 2008;186:271–3. [13] Scioscio V, Feraco P, Zompatori M, Miglio L, Toni F, Malvi D, Pacilli AM, Fasano L, Fabbri M. Benign metastasizing leiomyoma of the lung: PET findings. J Thorac Imaging 2009;24:41–4. [14] Lin X, Fan W, Lang P, Hu Y, Zhang X, Sun X. Benign metastasizing leiomyoma identified using 18 F-FDG PET/CT. Int J Gynaecol Obstet 2010;110:154–6. [15] Ogawa M, Shimizu S, Shibamoto Y, Haraa M, Ozawaa Y, Moriyamab S, Yano M. Benign metastasizing leiomyoma of the lung with malignant transformation mimicking mediastinal tumor. Clin Imaging 2011;35:401–4. [16] Funakoshi Y, Sawabata N, Takeda S, Hayakawa M, Okumura Y, Maeda H. Pulmonary benign metastasizing leiomyoma from the uterus in a postmenopausal woman: report of a case. Surg Today 2004;34:55–357. [17] Yoon G, Bae DS, Kim BG. Benign metastasizing leiomyoma with multiple lymph node metastasis: a case report. Cancer Res Treat 2011;43:131–3.
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
Pulmonary leiomyomas in a patient with bilateral renal cell cancer mimicking pulmonary metastases Ying-Yi Chen a, Seng-Tang Wu b, Hsian-Her Hsu c, Ya-Cheng Chen c, Shih-Chun Lee a, Hung Chang a, Tsai-Wang Huang a,⁎ a b c
Division of Thoracic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
a r t i c l e
i n f o
Article history: Received 21 October 2013 Received in revised form 10 January 2014 Accepted 15 January 2014 Keywords: Pulmonary leiomyoma Renal cell carcinoma Pulmonary metastasis
a b s t r a c t Pulmonary benign metastasizing leiomyoma (PBML) characterized by uterine leiomyoma in the lung is very rare. Here we report the case of a 55-year-old woman with a history of surgically resected multiple uterine leiomyomas who was histopathologically diagnosed with PBML associated with bilateral primary renal cell carcinoma (RCC). Clinicians should be aware of this unusual entity and consider pulmonary leiomyoma as a differential diagnosis in asymptomatic women with primary RCC and a history of hysterectomy for leiomyoma.
1. Introduction Pulmonary benign metastasizing leiomyoma (PBML) is a very rare disease characterized by the growth of uterine leiomyoma in the lungs [1]. Benign metastasizing leiomyoma (BML) was first identified by Steiner in 1939, and he believed it to be a primary pulmonary neoplasm. Therefore, BML was first referred to as fibroleiomyomatous hamartoma. Most patients present with a history of hysterectomy for uterine leiomyoma. However, the pathogenesis of this disease has not yet been elucidated. Here we report the case of a 55-year-old woman who underwent total abdominal hysterectomy for multiple uterine leiomyomas 10 years before presenting with bilateral renal cell carcinoma (RCC) and multiple shadows on a chest radiograph. These pulmonary nodules appeared to be distant metastases from the RCCs. This case report indicates that clinicians should be aware of this unusual entity and consider pulmonary leiomyoma as a differential diagnosis in an asymptomatic woman with primary RCC and a history of hysterectomy for leiomyoma. 2. Case report A 55-year-old woman presented with a 1-month history of general weakness, poor appetite, and weight loss (5 kg). She reported a ⁎ Corresponding author. Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, 325, Section 2, Cheng-Kung Road, Taipei 114, Taiwan, ROC. Tel.: +886 2 87927167; fax: +886 2 87927403. E-mail address: [email protected] (T.-W. Huang). 0899-7071/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clinimag.2014.01.008
© 2014 Elsevier Inc. All rights reserved.
history of hypertension that was being controlled with regular medication for 5 years; furthermore, she had been diagnosed with bilateral autosomal dominant polycystic disease (ADPKD) 7 years back and had undergone total abdominal hysterectomy for uterine leiomyomas accompanied by heavy and painful menstruation, painful sexual intercourse, and abnormal gynecological hemorrhage 10 years back. Physical examination revealed no rebounding tenderness over the abdomen, clear breath sounds in both lungs, and mildly pale conjunctiva. Urinalysis revealed no hematuria or pyuria. Abdominal sonography showed multiple hepatic and renal cysts and a solid nodule in each kidney. Plain chest radiography revealed bilateral, multiple, different-sized pulmonary nodules (Fig. 1). Abdominal magnetic resonance (MR) images of different sequences showed multiple, different-sized, hepatic (the largest measuring approximately 10.9 cm in the right lobe) and bilateral renal cystic lesions. In addition, a solid nodule measuring 7.8 cm and one measuring 3.1 cm were observed on the lower pole of the right kidney and in the sinus region of the left kidney, respectively (Fig. 2A–C). Sonography-guided needle biopsies were performed for both kidney nodules, which were histopathologically confirmed to be RCCs. The right and left lesions were chromophobe cell (CD10-negative; EMA-positive; vimentin, equivocal; CK7-positive) and conventional clear cell (CD10positive; EMA-positive; vimentin, positive; CK18-positive; pVHLpositive) RCCs, respectively. Bilateral, multiple pulmonary nodules and masses of different sizes (b3.6 cm) were observed with both central and peripheral distribution. Multiple, different-sized, hepatic cystic lesions were also observed on chest computed tomography (CT) (Fig. 3). A whole-body bone scan revealed no bone metastases. A CT-guided core
Y.2Y. Chen et al. / Clinical Imaging 38 (2014) 330–332
331
Fig. 1. Plain chest radiograph. The plain radiograph shows multiple scattered nodules of different sizes in both lung fields. Distribution is both central and peripheral, suggestive of pulmonary metastases.
needle biopsy was performed using an 18-gauge needle, but no definitive diagnosis was established. As a differential diagnosis, RCC with multiple pulmonary metastases was initially considered, and video-assisted thoracoscopic surgery with wedge resection of the right middle and lower lobes was performed to confirm the diagnosis and determine the treatment strategy. Postoperative histopathological examination revealed spindle-shaped cells with abundant clear cytoplasm and distinct cell borders, low mitotic activity (b 0–1/10 high power fields), little cytological cellular atypia, and no tumor cell necrosis. These pulmonary lesions were thus determined to be metastasizing leiomyomas according to the pathophysiology and immunohistochemical staining [actin-positive, CD10-negative, CK7-negative, PAX-2-negative, PAX-8-negative, vimentin-negative, CD117-negative, S-100-negative, HMB45-negative, estrogen receptor (ER)-positive; progesterone receptor (PR)-positive]. The PR and ER positivity indicated PBML. Therefore, the final diagnoses were as follows: (1) RCC, conventional type, left, stage cT1aN0M0; (2) RCC, chromophobe type, right, stage cT2aN0M0; and (3) bilateral PBML. A dynamic renal/urinary function test (99mTc-diethylenetriaminepentaacetic acid) for preoperative evaluation of differential renal function showed the following: (1) right kidney, moderately decreased blood flow and effective renal plasma flow (ERPF; 130 ml/min); (2) left kidney, moderately decreased blood flow and ERPF (123 ml/min); post-renal, marked obstruction and poor response to diuretics. The left RCC was centrally located and partially obstructed the upper urinary tract. This compromised renal function contraindicated immediate surgical resection. Therefore, a tyrosine-kinase inhibitor (TKI; pazopanib HCl) was prescribed to restore renal function, and partial nephrectomy of the right kidney was performed 3 months later. After 6 months, partial nephrectomy of the left kidney was performed under a stable condition and effective control by TKI. Regular follow-up was conducted on an outpatient basis; there was no tumor progression or recurrence for a year. 3. Discussion BML is a rare disease characterized by the appearance of relatively small pulmonary nodules several years after the removal of a histologically unremarkable uterus [2,3]. The mean duration between hysterectomy and the appearance of pulmonary lesions was report-
Fig. 2. Abdominal MR imaging. Two soft tissue masses, one measuring 3.1 cm in the parapelvic region of the left kidney (a) and one measuring 7.8 cm on the lower pole of the right kidney (b), along with enlargement of both kidneys with multiple cysts of different sizes (c), consistent with autosomal dominant polycystic disease, are observed. (A) T1-weighted coronal MR image shows mild hypointensity of the soft tissue lesions at both kidneys. (B) T2-weighted coronal MR image shows mild hyperintensity of the soft tissue lesions. (C) Contrast-enhanced T1-weighted coronal MR image shows enhancement of the soft tissue lesions over bilateral kidneys.
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Y.2Y. Chen et al. / Clinical Imaging 38 (2014) 330–332
Fig. 3. Coronal contrast-enhanced chest CT at the arterial phase of the soft tissue window. Multiple nodules and masses of different sizes (b3.6 cm) are scattered throughout both lungs, with both central and peripheral distribution (white arrow). Multiple cystic lesions of different sizes are seen in the liver, with the largest measuring approximately 10.9 cm in the right lobe (a).
edly 15 years [4]. There is no clear mechanism reported to underlie BML onset, and several different hypotheses are suggested. Some investigators have postulated that BMLs are actually low-grade leiomyosarcomas [4–6], while others consider pulmonary lesions to represent the intravascular spread of a benign uterine leiomyoma. The latter theory is similar to that for the origin of endometriosis at distant sites such as the lungs and postulates that BMLs and intravascular leiomyomatosis are related entities [7]. Diagnosing BML is very difficult, with strict pathological diagnostic criteria based on immunohistochemistry and a history of hysterectomy for uterine leiomyoma [8]. In our case, the housefield unit for the multiple pulmonary nodules on contrast-enhanced chest CT was + 30 (liver, + 50), and the pulmonary lesions were not contrast enhanced. The tumor cells were strongly positive for smooth muscle actin, confirming the smooth muscle origin. In addition, immunohistochemical staining revealed CD117 negativity, ruling out extragastrointestinal stromal tumor. All cells were S100 negative, essentially excluding a tumor of neural origin. The positive ER and PR immunoreactivity suggested that the spindle-shaped cells were uterine smooth muscle cells. Most pulmonary leiomyomas reported in the literature were associated with hereditary leiomyomatosis and RCC. Reed’s syndrome (or familial leiomyomatosis) is a rare inherited condition characterized by multiple cutaneous leiomyomas and, in women, uterine leiomyomas. This condition predisposes for RCC [9] and is also associated with an increased risk of uterine leiomyosarcoma [10]. The syndrome is caused by a mutation in the fumarate hydratase gene, which leads to fumarate accumulation. The inheritance pattern is autosomal dominant. This syndrome was ruled out for our patient because there was no family history of associated diseases and no associated skin lesions such as cutaneous leiomyomas. Except in patients with Reed’s syndrome, PBML with synchronous bilateral RCC has not been reported. Osadchy et al. [11] reported a case of PBML with left RCC. Several recent publications report notable findings on 18Ffluorodeoxyglucose positron emission tomography/CT (FDG PET-CT) [12–15]. However, another study reported that PET/CT [8] did not show abnormal FDG uptake, with an approximate standardized uptake value of 2. Also, Ogawa et al. [15] found that not all of these
pulmonary nodules comprised benign cells. FDG PET-CT could indicate a mild homogeneous and markedly elevated heterogeneous accumulation in the benign and malignant components, respectively. The heterogeneity may reflect necrosis within the tumor. Currently, there are no standard treatment guidelines for PBML. Reported modalities include careful observation, surgical resection, hysterectomy and bilateral oophorectomy, progestins, aromatase inhibitors, and medical castration with luteinizing hormone-releasing hormone analogs [16]. However, surgery combined with hormone therapy is considered optimal [17]. Renal masses of both kidneys were highly suspicious of malignancy related according to MR images before biopsy. The pulmonary nodules in our patient appeared to be distant metastases from RCC. Because CT-guided biopsy did not yield a conclusive diagnosis, surgical resection and histopathological examination allowed for precise clinical staging and appropriate management. In our patient, RCC subtype differed between both kidneys, requiring separate treatment. After achieving systemic control through targeted TKI therapy, partial nephrectomies were separately performed at a 6-month interval. In conclusion, clinicians should be aware of the possibility of this unusual entity, particularly in patients with RCC. Pulmonary leiomyoma should be considered as a differential diagnosis in an asymptomatic woman with primary RCC and a history of hysterectomy for leiomyoma. References [1] Steiner P. Metastasizing fibroleiomyoma of the uterus: report of a case and review of the literature. Am J Pathol 1939;15:89–107. [2] Abell MR, Littler ER. Benign metastasizing uterine leiomyoma. Multiple lymph nodal metastases. Cancer 1975;36:2206–13. [3] Nucci MR, Drapkin R, Cin PD, Fletcher CD, Fletcher JA. Distinctive cytogenetic profile in benign metastasizing leiomyoma: pathogenic implications. Am J Surg Pathol 2007;31:737–43. [4] Kayser K, Zink S, Schneider T, Dienemann H, André S, Kaltner H, Schüring MP, Zick Y, Gabius HJ. Benign metastasizing leiomyoma of the uterus: documentation of clinical, immunohistochemical and lectin-histochemical data of ten cases. Virchows Arch 2000;437:284–92. [5] Esteban JM, Allen WM, Schaerf RH. Benign metastasizing leiomyoma of the uterus: histologic and immunohistochemical characterization of primary and metastatic lesions. Arch Pathol Lab Med 1999;123:960–2. [6] Jautzke G, Muller-Ruchholtz E, Thalmann U. Immunohistological detection of estrogen and progesterone receptors in multiple and well differentiated leiomyomatous lung tumors in women with uterine leiomyomas. A report on 5 cases. Pathol Res Pract 1996;192:215–23. [7] Koh DM, Burn PR, King DM. Benign metastasizing leiomyoma with intracaval leiomyomatosis. Br J Radiol 2000;73:435–7. [8] Fu Y, Li H, Tian B, Hu B. Pulmonary benign metastasizing leiomyoma: a case report and review of the literature. World J Surg Oncol 2012;10:268. [9] Tolvanen J, Uimari O, Ryynänen M, Aaltonen LA, Vahteristo P. Strong family history of uterine leiomyomatosis warrants fumarate hydratase mutation screening. Hum Reprod 2012;27:1865–9. [10] Toro J, Nickerson M, Wei MH, Warren MB, Glenn GM, Turner ML, Stewart L, Duray P, Tourre O, Sharma N, Choyke P, Stratton P, Merino M, Walther MM, Linehan WM, Schimdt LS, Zbar B. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. Am J Hum Genet 2003;73:95–106. [11] Osadchy A, Zehavi T, Zissin R. Pulmonary benign metastasising leiomyomas presenting as fluid-containing masses on CT in a patient with two unrelated malignancies. Br J Radiol 2005;78:639–41. [12] Sapmaz F, Ergin M, Katrancioglu O, Gonlugur T, Gonlugur U, Elagoz S. Benign metastasizing leiomyoma. Lung 2008;186:271–3. [13] Scioscio V, Feraco P, Zompatori M, Miglio L, Toni F, Malvi D, Pacilli AM, Fasano L, Fabbri M. Benign metastasizing leiomyoma of the lung: PET findings. J Thorac Imaging 2009;24:41–4. [14] Lin X, Fan W, Lang P, Hu Y, Zhang X, Sun X. Benign metastasizing leiomyoma identified using 18 F-FDG PET/CT. Int J Gynaecol Obstet 2010;110:154–6. [15] Ogawa M, Shimizu S, Shibamoto Y, Haraa M, Ozawaa Y, Moriyamab S, Yano M. Benign metastasizing leiomyoma of the lung with malignant transformation mimicking mediastinal tumor. Clin Imaging 2011;35:401–4. [16] Funakoshi Y, Sawabata N, Takeda S, Hayakawa M, Okumura Y, Maeda H. Pulmonary benign metastasizing leiomyoma from the uterus in a postmenopausal woman: report of a case. Surg Today 2004;34:55–357. [17] Yoon G, Bae DS, Kim BG. Benign metastasizing leiomyoma with multiple lymph node metastasis: a case report. Cancer Res Treat 2011;43:131–3.
