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An interesting retroperitoneal mass Part 1
Pathology (February 2007) 39(1), pp. 164–167
TEST AND TEACH
An interesting retroperitoneal mass Part 1 KELLY MCCLYMONT*, IAN BROWN{{
AND
DAVID HUSSEY§
*Queensland Health Pathology Service, Royal Brisbane Hospital, {Department of Anatomical Pathology, Sullivan Nicolaides Pathology, {Department of Pathology, University of Queensland, and §Brisbane Private Hospital, Brisbane, Queensland, Australia
CASE REPORT A 45-year-old Caucasian woman living in Brisbane, Australia, presented to her general practitioner with increased urinary frequency and urgency over a 6-month period, not associated with haematuria or pain. Physical examination was unremarkable. Serial urine dipsticks, microscopy and cultures were normal. Pelvic ultrasound examination revealed a solid mass abutting the inferolateral aspect of the right kidney measuring up to 75 mm. Computed tomography showed the tumour at a higher resolution, and demonstrated focal involvement of the renal capsule and subjacent cortex. The radiological differential diagnosis was primary renal carcinoma, oncocytoma or connective tissue tumour (Fig. 1). The mass was removed as part of a radical nephrectomy. The resection specimen showed the tumour in retroperitoneal fat, attached to the capsular surface of the kidney, and bulging into subjacent renal parenchyma (Fig. 2). It was not encapsulated. Figures 3 and 4 show the H&E microscopic findings at medium and high power. Figure 5 demonstrates positivity of one of a panel of immunohistochemical stains (HMB45). Other stains performed but not shown included CAM5.2, vimentin, epithelial membrane antigen (EMA), CD10, CD56, synaptophysin, S-100, cytokeratin 7, cytokeratin 20 and neuron specific enolase (NSE). None of these stained positively. The patient did not have a personal
Fig. 1 CT of lesion adjacent to inferior pole of right kidney, with some contrast enhancement, but predominantly homogeneous internal architecture.
or family history of tuberous sclerosis. She remains well more than 12 months after the operation. Received 8 December, revised 21 December 2005, accepted 11 January 2006
See page 166 for explanation and diagnosis
Fig. 2 Tumour located at the inferior pole of the right kidney. The cut surface is soft, friable and pinkish-red. The tumour is well demarcated but there is no distinct capsule.
Fig. 3 Tumour displays relative homogeneity, with no areas of haemorrhage or necrosis. Occasional mature adipocytes are interspersed throughout the tissue (H&E, 6100).
ISSN 0031-3025 printed/ISSN 1465-3931 # 2007 Royal College of Pathologists of Australasia DOI: 10.1080/00313020601123847
TEST AND TEACH
Fig. 4 Large epithelioid cells with abundant eosinophilic cytoplasm and occasional bizarre cytological forms constitute the majority of the tumour (H&E, 6400).
Fig. 5
Strong, diffuse, positive staining for HMB45 (6200).
165
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Pathology (2007), 39(1), February
TEST AND TEACH
An interesting retroperitoneal mass Part 2
EXPLANATION AND DIAGNOSIS: EPITHELIOID ANGIOMYOLIPOMA OF THE RETROPERITONEUM Epithelioid angiomyolipoma (EAML, also known as primary monotypic epithelioid angiomyolipoma) is closely related to the more common classical angiomyolipoma (AML, also known as triphasic angiomyolipoma).1 EAML and AML are part of the group of perivascular epithelioid cell tumours (‘PEComas’), a designation that also includes clear cell sugar tumour of the lung,2 lymphangioleiomyomatosis3 and clear cell myomelanocytic tumour of the falciform ligament.4,5 Significant epidemiological differences exist between AML and EAML. AML and EAML are both associated with tuberous sclerosis (TS), but the association is stronger for EAML. More than half of all EAML cases are associated with TS.1 By contrast, TS association is seen in approximately 20% of cases in classical AML.6 Non-TS associated AML has a 4:1 female preponderance. Both TS associated AML and EAML occur with equal frequency in both sexes.1 Both sporadic and tuberous sclerosis-associated cases of EAML show monoclonal loss of heterozygosity of TSC2, a tumour suppressor gene on chromosome 16p13.3 whose function is lost by two-hit inactivation (obeying the Knudsen hypothesis).7,8 Where TSC1 and TSC2 mutations are inherited (in an autosomal dominant fashion), the patient may show other hamartomas and benign neoplasms such as subependymal giant cell astrocytoma, retinal glial hamartoma, as well as cardiac rhabdomyomas, hepatic, renal and pancreatic cysts. In the skin, angiofibroma, subungual fibroma, shagreen patches and ash-leaf patches are common.8 Both EAML and AML tend to involve the cortex or medulla of the kidney.9 The current case of retroperitoneal growth with focal renal attachment is a very rare growth pattern. One case of EAML in the retroperitoneum without renal involvement has been reported in the Japanese literature.10 EAML has also been reported in the liver,11 bone,12 ovary13 and uterus.14
The differential diagnosis of epithelial angiomyolipoma includes renal cell carcinoma and its variants, chromophobe carcinoma (eosinophilic variant), oncocytoma and renal medullary carcinoma.15 Table 1 compares selected features of the histopathology and immunohistochemistry of these lesions. Classic AML is an overwhelmingly benign lesion, despite rare cases of sarcomatous transformation. Occasional apparent ‘lymph node metastases’ may also be observed. These are usually regarded as a type of multifocal growth pattern in extra-renal tissue. Parenthetically, multifocal growth pattern of AML or EAML is strongly suggestive of TS.16 In contrast, EAML has a high malignant potential. Cases of EAML have metastasised (fatally) in more than one-third of patients, with reported sites of secondary involvement including lymph nodes, liver, lungs and spine.1 No particular morphological criteria or immunohistochemical profile has been yet identified to predict such behaviour. Non-malignant complications of AML and EAML include retroperitoneal bleeding and renal failure.1 EAML is a comparatively newly recognised entity, which is predominantly found in and around the kidney. Recognition of these and other PEComas requires thorough knowledge of the comparative gross and histological morphology and immunohistochemistry, as well as associated conditions. Key words: Epithelioid angiomyolipoma, primary monotypic epithelioid angiomyolipoma, renal, retroperitoneal, soft tissue, immunohistochemistry, Address for correspondence: Dr K. McClymont, Department of Anatomical Pathology, Queensland Health Pathology Service, Royal Brisbane Hospital, Brisbane, Qld 4000, Australia. E-mail: [email protected]
References 1. Amin MB. Epithelioid angiomyolipoma. In: Eble J.N, Sauter G, Epstein J.I. et al. World Health Organization Clasification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press, 2004: 68–9.
TABLE 1 Comparative features of EAML and differential diagnoses15,17,18 Tumour EAML Renal cell carcinoma Oncocytoma Renal medullary carcinoma Chromophobe carcinoma (eosinophilic variant)18
Morphology Occasional thick walled vessels and mature adipocytes; highly pleomorphic epithelioid cells and nuclei Delicate vascular network; tumour may form a distinctive pattern (e.g., alveolar, tubular, rhabdoid17) Regular nuclei with little variability Distinctive pattern: tubules, microcystic or reticular; absence of ‘ganglion-like cells’ and giant cells; sickle-cell trait may be apparent Characteristic binucleate cells with perinuclear halos and tight intercellular cohesion
CK, cytokeratins; EAML, epithelioid angiomyolipoma; EMA, epithelial membrane antigen.
Immunoprofile HMB45+, CD117?+, CK2, EMA2 HMB452, CK+, EMA+ HMB452, EMA2 HMB452, CK+, EMA+ HMB452, CK+, EMA+
TEST AND TEACH
2. Bonetti F, Pea M, Martignoni G, et al. Clear cell (‘sugar’) tumor of the lung is a lesion strictly related to angiomyolipoma—the concept of a family of lesions characterized by the presence of the perivascular epithelioid cells (PEC). Pathology 1994; 26: 230–6. 3. Chan JKC, Tsang WYW, Pay MY, et al. Lymphangiomatosis and angiomyolipoma: closely relative entities characterized by haemartomatous proliferation of HMB45-positive smooth muscle. Histopathology 1993; 22: 445–55. 4. Folpe AL, Goodman ZD, Ishak KG, et al. Clear cell myomelanocytic tumor of the falcifiorm ligament/ligamentum teres. A novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults. Am J Surg Pathol 2000; 24: 1239–46. 5. Tanaka Y, Ijiri R, Kato K, et al. HMB45/Melan A and smooth muscle actin-positive clear-cell epithelioid tumor arising in the ligament Teres Hepatis. Additional example of clear cell ‘sugar’ tumors. Am J Surg Pathol 2000; 24: 1295–9. 6. Kennelly MJ, Grossman HB, Cho KJ. Outcome analysis of 42 cases of renal angiomyolipoma. J Urology 1994; 152: 1988–91. 7. Henske EP, Neumann HP, Scheithauer BW, et al. Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band 16p13 occurs in sporadic as well as TSC-associated renal angiomyolipomas. Gene Chromosomes Cancer 1995; 13: 295–8. 8. Green AJ, Smith A, Yates JRW. Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients. Nat Genet 1994; 6: 193–6.
167
9. Mai KT, Perkins DG, Collins JP. Epithelioid cell variant of renal angiomyolipoma. Histopathology 1996; 28: 277–80. 10. Sanefuji T. Extrarenal retroperitoneal epithelial angiomyolipoma: a case report. (Japanese.) Acta Urol Japan 2003; 49: 201–5. 11. Yamasaki S, Tanaka S, Fujii H, et al. Monotypic epithelioid angiomyolipma of the liver. Histopathology 2000; 36: 451–6. 12. Insabato L, De Rosa G, Terracciano LM, et al. Primary monotypic epithelioid angiomyolipoma of bone. Histopathology 2002; 40: 286– 90. 13. Anderson AE, Yang X, Young RH. Epithelioid angiomyolipoma of the ovary: a case report and literature review. Int J Gynecol Pathol 2002; 21: 69–73. 14. Darai E, Bazot M, Barranger E, et al. Epithelioid angiomyolipoma of the uterus: a case report. J Reprod Med 2004; 49: 578–81. 15. Acikalin MF, Tel N, Oener U, et al. Epithelioid angiomyolipoma of the kidney. Int J Urol 2005; 12: 204–7. 16. Abdulla M, Bui HX, del Rosario AD, et al. Renal angiomyolipoma. DNA content and immunohistochemical study of classic and multicentric variants. Arch Pathol Lab Med 1994; 118: 735– 9. 17. Shannon B, Wisniewski ZS, Bentel J, et al. Adult rhabdoid renal cell carcinoma: divergent differentiation of conventional (clear-cell) carcinoma. Arch Pathol Lab Med 2002; 126: 1506–10. 18. Jimenez RE, Eble JN, Reuter VE, et al. Concurrent angiomyolipoma and renal cell neoplasia: a study of 36 cases. Mod Pathol 2001; 14: 157–63.
TEST AND TEACH
An interesting retroperitoneal mass Part 1 KELLY MCCLYMONT*, IAN BROWN{{
AND
DAVID HUSSEY§
*Queensland Health Pathology Service, Royal Brisbane Hospital, {Department of Anatomical Pathology, Sullivan Nicolaides Pathology, {Department of Pathology, University of Queensland, and §Brisbane Private Hospital, Brisbane, Queensland, Australia
CASE REPORT A 45-year-old Caucasian woman living in Brisbane, Australia, presented to her general practitioner with increased urinary frequency and urgency over a 6-month period, not associated with haematuria or pain. Physical examination was unremarkable. Serial urine dipsticks, microscopy and cultures were normal. Pelvic ultrasound examination revealed a solid mass abutting the inferolateral aspect of the right kidney measuring up to 75 mm. Computed tomography showed the tumour at a higher resolution, and demonstrated focal involvement of the renal capsule and subjacent cortex. The radiological differential diagnosis was primary renal carcinoma, oncocytoma or connective tissue tumour (Fig. 1). The mass was removed as part of a radical nephrectomy. The resection specimen showed the tumour in retroperitoneal fat, attached to the capsular surface of the kidney, and bulging into subjacent renal parenchyma (Fig. 2). It was not encapsulated. Figures 3 and 4 show the H&E microscopic findings at medium and high power. Figure 5 demonstrates positivity of one of a panel of immunohistochemical stains (HMB45). Other stains performed but not shown included CAM5.2, vimentin, epithelial membrane antigen (EMA), CD10, CD56, synaptophysin, S-100, cytokeratin 7, cytokeratin 20 and neuron specific enolase (NSE). None of these stained positively. The patient did not have a personal
Fig. 1 CT of lesion adjacent to inferior pole of right kidney, with some contrast enhancement, but predominantly homogeneous internal architecture.
or family history of tuberous sclerosis. She remains well more than 12 months after the operation. Received 8 December, revised 21 December 2005, accepted 11 January 2006
See page 166 for explanation and diagnosis
Fig. 2 Tumour located at the inferior pole of the right kidney. The cut surface is soft, friable and pinkish-red. The tumour is well demarcated but there is no distinct capsule.
Fig. 3 Tumour displays relative homogeneity, with no areas of haemorrhage or necrosis. Occasional mature adipocytes are interspersed throughout the tissue (H&E, 6100).
ISSN 0031-3025 printed/ISSN 1465-3931 # 2007 Royal College of Pathologists of Australasia DOI: 10.1080/00313020601123847
TEST AND TEACH
Fig. 4 Large epithelioid cells with abundant eosinophilic cytoplasm and occasional bizarre cytological forms constitute the majority of the tumour (H&E, 6400).
Fig. 5
Strong, diffuse, positive staining for HMB45 (6200).
165
166
Pathology (2007), 39(1), February
TEST AND TEACH
An interesting retroperitoneal mass Part 2
EXPLANATION AND DIAGNOSIS: EPITHELIOID ANGIOMYOLIPOMA OF THE RETROPERITONEUM Epithelioid angiomyolipoma (EAML, also known as primary monotypic epithelioid angiomyolipoma) is closely related to the more common classical angiomyolipoma (AML, also known as triphasic angiomyolipoma).1 EAML and AML are part of the group of perivascular epithelioid cell tumours (‘PEComas’), a designation that also includes clear cell sugar tumour of the lung,2 lymphangioleiomyomatosis3 and clear cell myomelanocytic tumour of the falciform ligament.4,5 Significant epidemiological differences exist between AML and EAML. AML and EAML are both associated with tuberous sclerosis (TS), but the association is stronger for EAML. More than half of all EAML cases are associated with TS.1 By contrast, TS association is seen in approximately 20% of cases in classical AML.6 Non-TS associated AML has a 4:1 female preponderance. Both TS associated AML and EAML occur with equal frequency in both sexes.1 Both sporadic and tuberous sclerosis-associated cases of EAML show monoclonal loss of heterozygosity of TSC2, a tumour suppressor gene on chromosome 16p13.3 whose function is lost by two-hit inactivation (obeying the Knudsen hypothesis).7,8 Where TSC1 and TSC2 mutations are inherited (in an autosomal dominant fashion), the patient may show other hamartomas and benign neoplasms such as subependymal giant cell astrocytoma, retinal glial hamartoma, as well as cardiac rhabdomyomas, hepatic, renal and pancreatic cysts. In the skin, angiofibroma, subungual fibroma, shagreen patches and ash-leaf patches are common.8 Both EAML and AML tend to involve the cortex or medulla of the kidney.9 The current case of retroperitoneal growth with focal renal attachment is a very rare growth pattern. One case of EAML in the retroperitoneum without renal involvement has been reported in the Japanese literature.10 EAML has also been reported in the liver,11 bone,12 ovary13 and uterus.14
The differential diagnosis of epithelial angiomyolipoma includes renal cell carcinoma and its variants, chromophobe carcinoma (eosinophilic variant), oncocytoma and renal medullary carcinoma.15 Table 1 compares selected features of the histopathology and immunohistochemistry of these lesions. Classic AML is an overwhelmingly benign lesion, despite rare cases of sarcomatous transformation. Occasional apparent ‘lymph node metastases’ may also be observed. These are usually regarded as a type of multifocal growth pattern in extra-renal tissue. Parenthetically, multifocal growth pattern of AML or EAML is strongly suggestive of TS.16 In contrast, EAML has a high malignant potential. Cases of EAML have metastasised (fatally) in more than one-third of patients, with reported sites of secondary involvement including lymph nodes, liver, lungs and spine.1 No particular morphological criteria or immunohistochemical profile has been yet identified to predict such behaviour. Non-malignant complications of AML and EAML include retroperitoneal bleeding and renal failure.1 EAML is a comparatively newly recognised entity, which is predominantly found in and around the kidney. Recognition of these and other PEComas requires thorough knowledge of the comparative gross and histological morphology and immunohistochemistry, as well as associated conditions. Key words: Epithelioid angiomyolipoma, primary monotypic epithelioid angiomyolipoma, renal, retroperitoneal, soft tissue, immunohistochemistry, Address for correspondence: Dr K. McClymont, Department of Anatomical Pathology, Queensland Health Pathology Service, Royal Brisbane Hospital, Brisbane, Qld 4000, Australia. E-mail: [email protected]
References 1. Amin MB. Epithelioid angiomyolipoma. In: Eble J.N, Sauter G, Epstein J.I. et al. World Health Organization Clasification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press, 2004: 68–9.
TABLE 1 Comparative features of EAML and differential diagnoses15,17,18 Tumour EAML Renal cell carcinoma Oncocytoma Renal medullary carcinoma Chromophobe carcinoma (eosinophilic variant)18
Morphology Occasional thick walled vessels and mature adipocytes; highly pleomorphic epithelioid cells and nuclei Delicate vascular network; tumour may form a distinctive pattern (e.g., alveolar, tubular, rhabdoid17) Regular nuclei with little variability Distinctive pattern: tubules, microcystic or reticular; absence of ‘ganglion-like cells’ and giant cells; sickle-cell trait may be apparent Characteristic binucleate cells with perinuclear halos and tight intercellular cohesion
CK, cytokeratins; EAML, epithelioid angiomyolipoma; EMA, epithelial membrane antigen.
Immunoprofile HMB45+, CD117?+, CK2, EMA2 HMB452, CK+, EMA+ HMB452, EMA2 HMB452, CK+, EMA+ HMB452, CK+, EMA+
TEST AND TEACH
2. Bonetti F, Pea M, Martignoni G, et al. Clear cell (‘sugar’) tumor of the lung is a lesion strictly related to angiomyolipoma—the concept of a family of lesions characterized by the presence of the perivascular epithelioid cells (PEC). Pathology 1994; 26: 230–6. 3. Chan JKC, Tsang WYW, Pay MY, et al. Lymphangiomatosis and angiomyolipoma: closely relative entities characterized by haemartomatous proliferation of HMB45-positive smooth muscle. Histopathology 1993; 22: 445–55. 4. Folpe AL, Goodman ZD, Ishak KG, et al. Clear cell myomelanocytic tumor of the falcifiorm ligament/ligamentum teres. A novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults. Am J Surg Pathol 2000; 24: 1239–46. 5. Tanaka Y, Ijiri R, Kato K, et al. HMB45/Melan A and smooth muscle actin-positive clear-cell epithelioid tumor arising in the ligament Teres Hepatis. Additional example of clear cell ‘sugar’ tumors. Am J Surg Pathol 2000; 24: 1295–9. 6. Kennelly MJ, Grossman HB, Cho KJ. Outcome analysis of 42 cases of renal angiomyolipoma. J Urology 1994; 152: 1988–91. 7. Henske EP, Neumann HP, Scheithauer BW, et al. Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band 16p13 occurs in sporadic as well as TSC-associated renal angiomyolipomas. Gene Chromosomes Cancer 1995; 13: 295–8. 8. Green AJ, Smith A, Yates JRW. Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients. Nat Genet 1994; 6: 193–6.
167
9. Mai KT, Perkins DG, Collins JP. Epithelioid cell variant of renal angiomyolipoma. Histopathology 1996; 28: 277–80. 10. Sanefuji T. Extrarenal retroperitoneal epithelial angiomyolipoma: a case report. (Japanese.) Acta Urol Japan 2003; 49: 201–5. 11. Yamasaki S, Tanaka S, Fujii H, et al. Monotypic epithelioid angiomyolipma of the liver. Histopathology 2000; 36: 451–6. 12. Insabato L, De Rosa G, Terracciano LM, et al. Primary monotypic epithelioid angiomyolipoma of bone. Histopathology 2002; 40: 286– 90. 13. Anderson AE, Yang X, Young RH. Epithelioid angiomyolipoma of the ovary: a case report and literature review. Int J Gynecol Pathol 2002; 21: 69–73. 14. Darai E, Bazot M, Barranger E, et al. Epithelioid angiomyolipoma of the uterus: a case report. J Reprod Med 2004; 49: 578–81. 15. Acikalin MF, Tel N, Oener U, et al. Epithelioid angiomyolipoma of the kidney. Int J Urol 2005; 12: 204–7. 16. Abdulla M, Bui HX, del Rosario AD, et al. Renal angiomyolipoma. DNA content and immunohistochemical study of classic and multicentric variants. Arch Pathol Lab Med 1994; 118: 735– 9. 17. Shannon B, Wisniewski ZS, Bentel J, et al. Adult rhabdoid renal cell carcinoma: divergent differentiation of conventional (clear-cell) carcinoma. Arch Pathol Lab Med 2002; 126: 1506–10. 18. Jimenez RE, Eble JN, Reuter VE, et al. Concurrent angiomyolipoma and renal cell neoplasia: a study of 36 cases. Mod Pathol 2001; 14: 157–63.