June 14, 2008
Tumor-to-Tumor Metastasis: Report of 2 Cases of Metastatic Carcinoma to Angiomyolipoma of the Kidney
By Ricketts, Reva Tamboli, Pheroze; Czerniak, Bogdan; Guo, Charles C
* Tumor-to-tumor metastasis is a rare phenomenon. Renal cell carcinoma is the most common recipient of tumor-totumor metastasis in malignant tumors. However, renal angiomyolipoma has not been reported to be a recipient. Here we report 2 cases of tumor-to- tumor metastasis to renal angiomyolipoma. In one case, the donor tumor originated from neuroendocrine carcinoma of the pancreas, and in the other case the donor tumor was from adenocarcinoma of the lung. The donor tumors showed morphologic features that did not easily fit into renal angiomyolipoma, and they also demonstrated patterns of immunoreactivity consistent with the primary tumors rather than with renal angiomyolipoma. To our knowledge, these are the first reported cases of tumor-to-tumor metastasis to renal angiomyolipoma. An awareness of this phenomenon is important to avoid an incorrect diagnosis when encountering unusual morphologic features in renal angiomyolipoma. (Arch Pathol Lab Med. 2008;132:1016-1020)
REPORT OF CASES
A 53-year-old man with a history of neuroendocrine carcinoma of the pancreas presented with an enlarging left renal mass. ee years previously, this patient developed a 6.3-cm tumor in the pancreas and multiple masses in the liver. Fine-needle aspiration biopsy of the liver masses revealed a low-grade neuroendocrine carcinoma, consistent with a metastasis from the pancreas primary. During the evaluation for neuroendocrine carcinoma of the pancreas, a 2.5-cm exophytic tumor was also identified at the upper pole of the left kidney. The patient subsequently received multiple rounds of chemotherapy for the metastatic neuroendocrine carcinoma, and his condition improved. The renal tumor remained unchanged in follow-up imaging studies until 2 1/2 years later, when the tumor increased to a size of 3.5 cm. On computed tomography (CT), no adipose tissue was identified in this renal mass. Therefore, this tumor was thought most likely to be a renal cell carcinoma. Additional radiographic studies showed that the tumors in the pancreas and liver did not progress. The patient elected to undergo a partial nephrectomy.
A 75-year-old man developed a dry cough accompanied with shortness of breath a year prior to presentation. At that time the patient was suspected of having pneumonia and had been treated with multiple antibiotics. Unfortunately, his cough did not improve. A CT scan of the abdomen demonstrated a 4.5-cm mass in the superior pole of the right kidney. His bone scan revealed multiple focal areas of increased activity in the thoracic spine, ribs, and right iliac crest, suspicious for metastatic disease. He underwent a CT-guided renal biopsy.
The partial nephrectomy specimen in case 1 measured 6.0 x 3.5 x 3.0 cm. Sectioning revealed a gray-white circumscribed mass measuring 3.5 x 2.6 x 2.1 cm. This exophytic tumor pushed against but did not penetrate the renal capsule. The cut surface was firm and granular without hemorrhage or necrosis. Microscopically, the tumor was composed largely of smooth muscle cells and thickwalled blood vessels with scant adipose tissue (Figure 1, A). The smooth muscle cells were intimately associated with the outer layers of the muscular walls of blood vessels. Intracytoplasmic vacuoles were also present in some smooth muscle cells. These features are consistent with angiomyolipoma of the kidney. However, within the angiomyolipoma, there were small foci of atypical cells arranged in trabecular, insular, or acinar patterns (Figure 1, B). These cells exhibited amphophilic cytoplasm and uniform nuclei with granular chromatin and inconspicuous nucleoli, which were suggestive of neuroendocrine cells. The atypical cells were not identified in the nonneoplastic renal parenchyma. Immunohistochemical studies were performed. The majority of the tumor showed positive signals for HMB- 45 and negative signals for cytokeratin, consistent with an angiomyolipoma. However, those small foci of neuroendocrine-like cells were diffusely positive for pancytokeratin (Figure 1, C), MOC- 31, synaptophysin (Figure 1, D), and CD56; focally positive for chromogranin and AE1/AE3; and negative for HMB-45. Therefore, these foci of atypical cells represented metastatic neuroendocrine carcinoma from the pancreas. After this partial nephrectomy, the patient's previous fine-needle aspiration of liver masses was reviewed and demonstrated atypical cells with similar neuroendocrine features (Figure 1, E), and these atypical cells were positive for cytokeratin and synaptophysin (Figure 1, F), consistent with metastatic neuroendocrine carcinoma from the pancreas.
The renal biopsy specimen in case 2 consisted of multiple fragments of soft tan-pink tissue (0.5 x 0.1 x 0.1 cm in aggregate). Microscopically, the tumor was mostly composed of spindle cells, thick-walled blood vessels, and adipose tissue, admixed in a haphazard fashion, consistent with an angiomyolipoma (Figure 2, A). In addition, there are atypical nested epithelioid cells with enlarged hyperchromatic nuclei (Figure 2, B). On immunostains, the majority of the tumor was positive for smooth muscle actin and HMB-45 and negative for cytokeratin, consistent with renal angiomyolipoma. In contrast, those small foci of atypical cells showed strong positive signals for pancytokeratin and cytokeratin 7 (Figure 2, C), and negative signals for smooth muscle actin and HMB-45. In addition, these atypical cells were also positive for thyroid transcription factor 1 (Figure 2, D) and surfactant, supporting a metastasis of lung primary. Subsequently, a CT scan of the chest was performed and demonstrated a 3.5 x 2.1- cm nodular area with consolidation in the left upper lung. This lung mass was biopsied by fine-needle aspiration and cytology examination revealed malignant cells with enlarged round nuclei and prominent nucleoli (Figure 2, E). These malignant cells were positive for thyroid transcription factor 1 (Figure 2, F), consistent with adenocarcinoma of the lung.
Angiomyolipoma is a benign mesenchymal tumor composed of various combinations of adipose tissue, smooth muscle cells, and characteristic thick-walled blood vessels. 5 Angiomyolipomas occur most often in the kidney, but they have also been found in the liver, ovary, fallopian tube, spermatic cord, palate, and colon. Renal angiomyolipomas, such as the previous 2 cases, are usually asymptomatic and discovered by radiographic screening techniques. The demonstration of adipose tissue in a renal mass on radiographic images excludes renal cell carcinoma and is indicative of angiomyolipoma. However, in rare cases of angiomyolipoma, the tumor may be composed mostly of smooth muscle cells and thick-walled blood vessels, with minimal adipose tissue. In such cases, angiomyolipoma is often confused with renal cell carcinoma on radiographic imaging, thus leading to unnecessary surgical excision.6
The presence of predominant epithelioid cells in angiomyolipoma has led to the recognition of epithelioid angiomyolipoma, a malignant tumor with the capacity to be locally aggressive and metastasize.7 Epithelioid angiomyolipoma is usually composed of round to polygonal cells with abundant acidophilic cytoplasm in sheets. The tumor cells have enlarged vesicular nuclei with prominent nucleoli, resembling ganglion cells. Epithelioid angiomyolipoma has a pattern of immunoreactivity similar to that of the usual angiomyolipoma: positive staining for melanoma markers (HMB-45, Melan-A, and tyrosinase) and smooth muscle markers (smooth muscle actin and musclespecific actin). Epithelioid angiomyolipoma usually lacks immunoreactivity for cytokeratins. In the 2 cases we present, the atypical cells show diffuse and strong positive reactivity for cytokeratins (pancytokeratin, MOC-31, AE1/ AE3, and cytokeratin 7) and negative reactivity for smooth muscle actin and HMB-45. These immunoreactive patterns are more compatible with metastatic carcinoma rather than epithelioid angiomyolipoma.
Another possibility to consider in the case of unusual morphology in angiomyolipoma is a collision tumor. A collision tumor results when 2 morphologically distinct tumors develop in the same location. This phenomenon has been documented in the kidney. In a study of 36 cases of concurrent angiomyolipoma and malignant renal tumors, Jimenez et al8 found that clear cell renal cell carcinoma was the most common malignancy, accounting for approximately two thirds of the tumors. In most clinical settings, angiomyolipoma was an incidental finding. In the 2 cases we describe, the specimens were thoroughly examined, and no renal cell carcinoma is present. In addition, immunohistochemical studies demonstrate patterns of immunoreactivity that are consistent with the patients' known primary tumors: the tumor in case 1 shows reactivity for neuroendocrine markers (synaptophysin, chromogranin, and CD56), consistent with neuroendocrine carcinoma of the pancreas; the tumor in case 2 shows positive reactivity for cytokeratin 7, thyroid transcription factor 1, and surfactant, consistent with adenocarcinoma of the lung. At the advanced stage, malignant tumors may metastasize to the kidney. In a study of 11 328 autopsies of cancer patients, Bracken et al9 found that 7.2% of the patients had metastases from the primary tumors to the kidney. Virtually any carcinoma can metastasize to the kidney. However, the most common primary tumors to metastasize to the kidney were tumors of the lung, breast, and skin (melanoma). Up to 28% of renal cell carcinomas metastasized to the opposite kidney. Generally, metastatic tumors were multiple, bilateral, less than 3 cm, and presented throughout in the renal parenchyma. When a renal tumor presents with unusual morphologic features as a primary lesion, the possibility of metastasis should always be considered.
Tumor-to-tumor metastasis is a rare phenomenon. Although any tumor may be a potential recipient of metastasis, renal cell carcinoma is by far the most common recipient among malignant tumors. Two factors may contribute to the preferential homing of metastatic cancer to renal cell carcinoma: one is the rich vascularization of renal cell carcinomas, which renders them more accessible to metastatic tumor cells in the circulating blood, and the other is the high lipid and glycogen content in renal cell carcinoma, which may provide a nutrient-rich microenvironment for metastatic tumor cells. Because angiomyolipomas are also characterized by rich vascularization and abundant lipid content, they too may be suitable hosts for metastases. However, most renal angiomyolipomas are identified by CT scan and are usually not resected. The extreme rarity of tumor metastasis to angiomyolipoma is probably because renal angiomyolipoma is underestimated in surgical series, accounting for less than 1% of all tumors surgically removed from the kidney.
In summary, we present 2 cases of tumor-to-tumor metastasis to angiomyolipoma of the kidney. To the best of our knowledge, this is the first report of tumor-to-tumor metastasis into renal angiomyolipoma. Although tumorto- tumor metastasis is extremely rare, an awareness of this phenomenon is important to avoid an incorrect diagnosis when encountering a tumor with a strikingly dimorphic appearance.
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Reva Ricketts, DO; Pheroze Tamboli, MD; Bogdan Czerniak, MD, PhD; Charles C. Guo, MD
Accepted for publication December 17, 2007.
From the Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston.
The authors have no relevant financial interest in the products or companies described in this article.
Reprints: Charles C. Guo, MD, Department of Pathology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 085, Houston, TX 77030 (e-mail: [email protected]).
Copyright College of American Pathologists Jun 2008
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