572224
research-article2015
IJSXXX10.1177/1066896915572224International Journal of Surgical PathologyWu and Pan
Case Report
Lung Adenocarcinoma Metastasizing Into a Renal Angiomyolipoma
International Journal of Surgical Pathology 2015, Vol. 23(3) 230–233 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896915572224 ijs.sagepub.com
Pao-Shu Wu, MD, PhD1, and Chin-Chen Pan, MD1
Abstract Tumor-to-tumor metastasis is a very rare phenomenon. The most common donor and recipient of tumor-totumor metastasis are carcinomas of lung and renal cell carcinoma, respectively. We report a case of primary lung adenocarcinoma that metastasized into a renal angiomyolipoma 9 years after the resection of primary lung tumor. Comparisons in morphology, immunohistochemical profiles, and genetic mutations indicate that the tumor metastasizing into angiomyolipoma originated from the same clone of previous lung adenocarcinoma. Albeit rare, pathologists should be aware of the possibility of tumor-to-tumor metastasis when confronting a neoplasm exhibiting 2 distinct morphological features. Keywords tumor-to-tumor metastasis, adenocarcinoma, angiomyolipoma, kidney, lung
Introduction Tumor-to-tumor metastasis is a rare phenomenon. There have been less than 100 cases reported up to date since its first description in 1902 by Berent.1 Histopathologically, a true tumor-to-tumor metastasis should satisfy the following 4 criteria proposed by Cambell et al2: (a) there should be more than one primary tumor; (b) the recipient tumor is a true neoplasm, either benign or malignant; (c) the metastatic tumor is a true metastasis with established growth in the recipient tumor, not just the result of contiguous growth (collision tumor) or embolism of neoplastic cells in the recipient tumor; and (d) tumors that have metastasized to lymphatic systems where lymphoreticular malignant tumors already exist are excluded. Herein we report a case of primary lung adenocarcinoma that metastasized into a renal angiomyolipoma. There was a 9-year interval between the resection of primary lung tumor and the metastasis to renal angiomyolipoma. We compared the morphology, immunohistochemical profiles, and molecular pathology properties of the 2 lesions.
Case Report A 73-year-old woman underwent the right lower lobe lobectomy and right side lymph node dissection for lung adenocarcinoma (pT2N0M0; Figure 1A). She did not receive adjuvant radiation or chemotherapy. Regular image follow-up and tumor survey showed no evidence of tumor metastasis or recurrence until 9 years after operation, when
a computed tomography examination revealed an enlarging lobulated cystic mass, measuring about 12 cm, in the upper pole of the right kidney. A cystic renal cell carcinoma was considered and the patient underwent right radical nephrectomy. The kidney measured 10.5 × 4.8 × 3.5 cm with a protruding yellow-white cystic mass, 10 × 8 × 8 cm. Microscopically, the tumor showed haphazard distribution of smooth muscle cells, thick-walled hyalinized blood vessels, and mature adipose tissue consistent with an angiomyolipoma. Aside from angiomyolipoma, there was an adenocarcinoma exhibiting papillary architecture lined by tumor cells with eosinophilic cytoplasm, enlarged vesicular nuclei, and prominent nucleoli. The angiomyolipoma and adenocarcinoma intermingled within each other (Figure 1B). Morphologically, the adenocarcinoma is consistent with the previous lung adenocarcinoma. Immunohistochemically, smooth muscle actin and HMB45 highlighted the angiomyolipoma component (Figure 1C). The adenocarcinoma component was positive for cytokeratin 7 and thyroid transcription factor-1 (Figure 1D), compatible with pulmonary origin. The adenocarcinoma was negative for renal cell carcinoma marker, CD10, carbonic anhydrase 9, and α-methylacyl-CoA racemase. Molecular 1
Taipei Veterans General Hospital, Taipei, Taiwan
Corresponding Author: Chin-Chen Pan, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei City 11217, Taiwan. Email: [email protected]
Wu and Pan
231
Figure 1. (A) The primary lung adenocarcinoma shows papillary and micropapillary growth patterns. (B) The angiomyolipoma showed mixture of smooth muscle, adipose tissue, and thick-walled hyalinized blood vessels, intermingled with an adenocarcinoma morphologically similar to the lung adenocarcinoma (H&E, 100×). (C) HMB-45 immunoreactivity in the angiomyolipoma. (D) Nuclear positivity for thyroid transcription factor-1 in the adenocarcinoma (Immunoperoxidate, 200×).
analyses using Scorpion Amplification Refractory Mutation System (SARMS) technology revealed that both the primary lung adenocarcinoma and its metastasis in the renal angiomyolipoma carried the same epidermal growth factor receptor (EGFR) exon 19 deletion (Figure 2A). Using antibody specific for EGFR exon 19 deletion also demonstrated positive signals in the metastasis in the angiomyolipoma (Figure 2B). The patient received postoperative tyrosine kinase inhibitor target therapy (gefitinib and erlotinib) combined with chemotherapy of cisplantin and pemetrexed regime for 3 cycles. The patient has been free of metastasis for 3 years.
Discussion In theory, any benign or malignant neoplasm can be the recipient of tumor-to-tumor metastasis. The most common malignant and benign recipient neoplasms are renal clear cell carcinoma and meningioma, respectively.3,4 The most common donor neoplasm is carcinoma of lung, followed by carcinoma of breast, gastrointestinal tract, prostate, and thyroid.5 Tumor metastasizing into an angiomyolipoma is extremely rare. Only 2 cases have been reported in the English literature up to date, and the donor neoplasms were
neuroendocrine carcinoma of pancreas and lung adenocarcinoma.6 Both cases showed concomitant presence of the angiomyolipoma and extrarenal donor tumors. In our case, however, no extrarenal lesions were found when the renal tumor was excised. The morphological features, immunohistochemical profiles, and the identical EGFR mutation indicate that the tumor metastasizing into angiomyolipoma originated from the same clone of previous lung adenocarcinoma. Two not mutually exclusive theories have been proposed for the underlying mechanisms of tumor-to-tumor metastasis. The first is the “seed and soil” theory, suggesting that the metastatic tumor cells (seeds) favor a suitable milieu or niche (soil) for their growth and proliferation.7,8 The second theory, “mechanical entrapment theory,” suggests that the site of tumor metastasis is dependent on how easily the tumor cells can access organs with rich vasculature and high blood flow.8,9 Angiomyolipoma is a neoplasm with abundant blood supply; however, given angiomyolipoma accounts for less than 1% of surgically removed renal tumors,10 it is a less common recipient compared with renal cell carcinoma. The cystic presentation of angiomyolipoma prompts the differential diagnosis of angiomyolipoma with epithelial
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Figure 2. (A) Scorpion ARMS revealed both primary lung adenocarcinoma and its metastasis in the angiomyolipoma share the same EGFR exon 19 deletion. (B) The metastasizing adenocarcinoma in the angiomyolipoma is immunoreactive for EGFR exon 19 deletion (Immunoperoxidate, 200×).
cysts (AMLEC), a rare angiomyolipoma variant.11 AMLEC is characterized by epithelial cysts with cuboidal to hobnail lining cells of presumably renal tubular cell origin, a compact subepithelial “cambium-like” layer of cellular stroma, and a muscle-predominant angiomyolipoma. In present case, the complex proliferative branching architecture of the adenocarcinoma, lack of subepithelial cambium-like layer stroma, and ancillary immunohistochemical and molecular studies ruled out the possibility of AMLEC. Tumor-to-tumor metastasis should be distinguished from a collision tumor. A collision tumor results from 2 morphologically distinct and originally separate tumors appear to develop coincidently in close proximity.2,3,6 In summary, we describe a case of a lung adenocarcinoma that metastasized to a renal angiomyolipoma 9 years after surgical removal of the primary lung tumor. Albeit rare, pathologists should be aware of the possibility of tumor-to-tumor metastasis when confronting a neoplasm exhibiting 2 entirely distinct morphological features. Thorough medical record reviewing, morphology comparison, ancillary immunohistochemical, and molecular studies can facilitate an accurate diagnosis.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Berent W. Seltene metastsenbildung. Zentralbl Allg Pathol. 1902;13:406-410. 2. Cambell LV, Gilbert E, Chamberlain CR, Watne AL. Metastases of cancer to cancer. Cancer. 1968;22:635-643. 3. Granville LA, Ostrowski ML, Truong LD, Shen S. Unusual morphology in an otherwise classic renal cell carcinoma. Arch Pathol Lab Med. 2005;129:e49-e50. 4. Sella A, Ro JY. Renal cell cancer: best recipient of tumor-totumor metastasis. Urology. 1987;20:35-38. 5. Ichijima K, Yamabe H, Kobashi Y, Iwata T. Metastasis of cancer to cancer. Acta Pathol Jpn. 1980;30:293-300. 6. Ricketts R, Tamboli P, Czerniak B, Guo CC. Tumor-totumor metastasis: report of 2 cases of metastatic carcinoma
Wu and Pan to angiomyolipoma of the kidney. Arch Pathol Lab Med. 2008;132:1016-1020. 7. Paget S. The distribution of secondary growths in cancer of the breast. Lancet. 1889;1:571-573. 8. Fidler I. The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nat Rev Cancer. 2003;3:453-458. 9. Ewing JA. A Treatise on Tumors. Philadelphia, PA: Saunders; 1928.
233 10. Eble JN, Sauter G, Epstein JI, Sesterhenn IA. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon, France: IARC Press; 2003. 11. Fine SW, Reuter VE, Epstein JI, Argani P. Angiomyolipoma with epithelial cysts (AMLEC): a distinct cystic variant of angiomyolipoma. Am J Surg Pathol. 2006;30: 593-599.
Copyright of International Journal of Surgical Pathology is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
research-article2015
IJSXXX10.1177/1066896915572224International Journal of Surgical PathologyWu and Pan
Case Report
Lung Adenocarcinoma Metastasizing Into a Renal Angiomyolipoma
International Journal of Surgical Pathology 2015, Vol. 23(3) 230–233 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896915572224 ijs.sagepub.com
Pao-Shu Wu, MD, PhD1, and Chin-Chen Pan, MD1
Abstract Tumor-to-tumor metastasis is a very rare phenomenon. The most common donor and recipient of tumor-totumor metastasis are carcinomas of lung and renal cell carcinoma, respectively. We report a case of primary lung adenocarcinoma that metastasized into a renal angiomyolipoma 9 years after the resection of primary lung tumor. Comparisons in morphology, immunohistochemical profiles, and genetic mutations indicate that the tumor metastasizing into angiomyolipoma originated from the same clone of previous lung adenocarcinoma. Albeit rare, pathologists should be aware of the possibility of tumor-to-tumor metastasis when confronting a neoplasm exhibiting 2 distinct morphological features. Keywords tumor-to-tumor metastasis, adenocarcinoma, angiomyolipoma, kidney, lung
Introduction Tumor-to-tumor metastasis is a rare phenomenon. There have been less than 100 cases reported up to date since its first description in 1902 by Berent.1 Histopathologically, a true tumor-to-tumor metastasis should satisfy the following 4 criteria proposed by Cambell et al2: (a) there should be more than one primary tumor; (b) the recipient tumor is a true neoplasm, either benign or malignant; (c) the metastatic tumor is a true metastasis with established growth in the recipient tumor, not just the result of contiguous growth (collision tumor) or embolism of neoplastic cells in the recipient tumor; and (d) tumors that have metastasized to lymphatic systems where lymphoreticular malignant tumors already exist are excluded. Herein we report a case of primary lung adenocarcinoma that metastasized into a renal angiomyolipoma. There was a 9-year interval between the resection of primary lung tumor and the metastasis to renal angiomyolipoma. We compared the morphology, immunohistochemical profiles, and molecular pathology properties of the 2 lesions.
Case Report A 73-year-old woman underwent the right lower lobe lobectomy and right side lymph node dissection for lung adenocarcinoma (pT2N0M0; Figure 1A). She did not receive adjuvant radiation or chemotherapy. Regular image follow-up and tumor survey showed no evidence of tumor metastasis or recurrence until 9 years after operation, when
a computed tomography examination revealed an enlarging lobulated cystic mass, measuring about 12 cm, in the upper pole of the right kidney. A cystic renal cell carcinoma was considered and the patient underwent right radical nephrectomy. The kidney measured 10.5 × 4.8 × 3.5 cm with a protruding yellow-white cystic mass, 10 × 8 × 8 cm. Microscopically, the tumor showed haphazard distribution of smooth muscle cells, thick-walled hyalinized blood vessels, and mature adipose tissue consistent with an angiomyolipoma. Aside from angiomyolipoma, there was an adenocarcinoma exhibiting papillary architecture lined by tumor cells with eosinophilic cytoplasm, enlarged vesicular nuclei, and prominent nucleoli. The angiomyolipoma and adenocarcinoma intermingled within each other (Figure 1B). Morphologically, the adenocarcinoma is consistent with the previous lung adenocarcinoma. Immunohistochemically, smooth muscle actin and HMB45 highlighted the angiomyolipoma component (Figure 1C). The adenocarcinoma component was positive for cytokeratin 7 and thyroid transcription factor-1 (Figure 1D), compatible with pulmonary origin. The adenocarcinoma was negative for renal cell carcinoma marker, CD10, carbonic anhydrase 9, and α-methylacyl-CoA racemase. Molecular 1
Taipei Veterans General Hospital, Taipei, Taiwan
Corresponding Author: Chin-Chen Pan, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei City 11217, Taiwan. Email: [email protected]
Wu and Pan
231
Figure 1. (A) The primary lung adenocarcinoma shows papillary and micropapillary growth patterns. (B) The angiomyolipoma showed mixture of smooth muscle, adipose tissue, and thick-walled hyalinized blood vessels, intermingled with an adenocarcinoma morphologically similar to the lung adenocarcinoma (H&E, 100×). (C) HMB-45 immunoreactivity in the angiomyolipoma. (D) Nuclear positivity for thyroid transcription factor-1 in the adenocarcinoma (Immunoperoxidate, 200×).
analyses using Scorpion Amplification Refractory Mutation System (SARMS) technology revealed that both the primary lung adenocarcinoma and its metastasis in the renal angiomyolipoma carried the same epidermal growth factor receptor (EGFR) exon 19 deletion (Figure 2A). Using antibody specific for EGFR exon 19 deletion also demonstrated positive signals in the metastasis in the angiomyolipoma (Figure 2B). The patient received postoperative tyrosine kinase inhibitor target therapy (gefitinib and erlotinib) combined with chemotherapy of cisplantin and pemetrexed regime for 3 cycles. The patient has been free of metastasis for 3 years.
Discussion In theory, any benign or malignant neoplasm can be the recipient of tumor-to-tumor metastasis. The most common malignant and benign recipient neoplasms are renal clear cell carcinoma and meningioma, respectively.3,4 The most common donor neoplasm is carcinoma of lung, followed by carcinoma of breast, gastrointestinal tract, prostate, and thyroid.5 Tumor metastasizing into an angiomyolipoma is extremely rare. Only 2 cases have been reported in the English literature up to date, and the donor neoplasms were
neuroendocrine carcinoma of pancreas and lung adenocarcinoma.6 Both cases showed concomitant presence of the angiomyolipoma and extrarenal donor tumors. In our case, however, no extrarenal lesions were found when the renal tumor was excised. The morphological features, immunohistochemical profiles, and the identical EGFR mutation indicate that the tumor metastasizing into angiomyolipoma originated from the same clone of previous lung adenocarcinoma. Two not mutually exclusive theories have been proposed for the underlying mechanisms of tumor-to-tumor metastasis. The first is the “seed and soil” theory, suggesting that the metastatic tumor cells (seeds) favor a suitable milieu or niche (soil) for their growth and proliferation.7,8 The second theory, “mechanical entrapment theory,” suggests that the site of tumor metastasis is dependent on how easily the tumor cells can access organs with rich vasculature and high blood flow.8,9 Angiomyolipoma is a neoplasm with abundant blood supply; however, given angiomyolipoma accounts for less than 1% of surgically removed renal tumors,10 it is a less common recipient compared with renal cell carcinoma. The cystic presentation of angiomyolipoma prompts the differential diagnosis of angiomyolipoma with epithelial
232
International Journal of Surgical Pathology 23(3)
Figure 2. (A) Scorpion ARMS revealed both primary lung adenocarcinoma and its metastasis in the angiomyolipoma share the same EGFR exon 19 deletion. (B) The metastasizing adenocarcinoma in the angiomyolipoma is immunoreactive for EGFR exon 19 deletion (Immunoperoxidate, 200×).
cysts (AMLEC), a rare angiomyolipoma variant.11 AMLEC is characterized by epithelial cysts with cuboidal to hobnail lining cells of presumably renal tubular cell origin, a compact subepithelial “cambium-like” layer of cellular stroma, and a muscle-predominant angiomyolipoma. In present case, the complex proliferative branching architecture of the adenocarcinoma, lack of subepithelial cambium-like layer stroma, and ancillary immunohistochemical and molecular studies ruled out the possibility of AMLEC. Tumor-to-tumor metastasis should be distinguished from a collision tumor. A collision tumor results from 2 morphologically distinct and originally separate tumors appear to develop coincidently in close proximity.2,3,6 In summary, we describe a case of a lung adenocarcinoma that metastasized to a renal angiomyolipoma 9 years after surgical removal of the primary lung tumor. Albeit rare, pathologists should be aware of the possibility of tumor-to-tumor metastasis when confronting a neoplasm exhibiting 2 entirely distinct morphological features. Thorough medical record reviewing, morphology comparison, ancillary immunohistochemical, and molecular studies can facilitate an accurate diagnosis.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Berent W. Seltene metastsenbildung. Zentralbl Allg Pathol. 1902;13:406-410. 2. Cambell LV, Gilbert E, Chamberlain CR, Watne AL. Metastases of cancer to cancer. Cancer. 1968;22:635-643. 3. Granville LA, Ostrowski ML, Truong LD, Shen S. Unusual morphology in an otherwise classic renal cell carcinoma. Arch Pathol Lab Med. 2005;129:e49-e50. 4. Sella A, Ro JY. Renal cell cancer: best recipient of tumor-totumor metastasis. Urology. 1987;20:35-38. 5. Ichijima K, Yamabe H, Kobashi Y, Iwata T. Metastasis of cancer to cancer. Acta Pathol Jpn. 1980;30:293-300. 6. Ricketts R, Tamboli P, Czerniak B, Guo CC. Tumor-totumor metastasis: report of 2 cases of metastatic carcinoma
Wu and Pan to angiomyolipoma of the kidney. Arch Pathol Lab Med. 2008;132:1016-1020. 7. Paget S. The distribution of secondary growths in cancer of the breast. Lancet. 1889;1:571-573. 8. Fidler I. The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nat Rev Cancer. 2003;3:453-458. 9. Ewing JA. A Treatise on Tumors. Philadelphia, PA: Saunders; 1928.
233 10. Eble JN, Sauter G, Epstein JI, Sesterhenn IA. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon, France: IARC Press; 2003. 11. Fine SW, Reuter VE, Epstein JI, Argani P. Angiomyolipoma with epithelial cysts (AMLEC): a distinct cystic variant of angiomyolipoma. Am J Surg Pathol. 2006;30: 593-599.
Copyright of International Journal of Surgical Pathology is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
![[Renal angiomyolipoma].](/assets/img/hold.png)
