Fine-Needle Aspiration Biopsy Diagnosis of Malignant Rhabdoid Tumor of the Kidney Mohammed Akhtar, M.D., F.C.A.P., Muhammad Ashraf Ali, M.D., F.R.C.P. (c.), Kwesi Sackey, M.B., ch.B., F.A.A.P., Mohammed Bakry, M.B., B.S., and Anwar Burgess, C.T. (A.s.c.P.) (I.A.c.)
A series of six fine-needle aspiration biopsiesfrom three patients with malignant rhabdoid tumor of the kidney is reviewed. The smears revealed round, polygonal, and irregularly shaped cells with large nuclei andprominent nucleoli. Some of the tumor cells contained light pink to purple cytoplasmic inclusions that correlated with the eosinophilic inclusions seen in histopathologic sections and filamentous cytoplasmic aggregates noted on ultrastructural examination. Diagnosis of malignant rhabdoid tumor of the kidney may be suggested from aspiration biopsy smears; however, further conJrmation of the diagnosis by histologic or ultrastructural examination is desirable. Diagn Cytopathol 1991; 7:36-40.
Key Words: Rhabdoid tumor; Kidney; Fine-needle aspiration; Biopsy; Filamentous inclusions
Malignant rhabdoid tumor of the kidney (MRTK) was characterized by Beckwith and Palmer in 1978 as a highly aggressive variant of Wilms’ tumor, but it was later recognized as a separate entity. 2,3 MRTK presents clinically as an abdominal or flank mass that is indistinguishable from Wilms’ tumor and other renal neoplasms encountered in infants and children. Histologically, the tumor is composed of cells arranged in a sheet-like fashion and characterized by a moderate amount of eosinophilic cytoplasm and large vesicular nuclei with prominent nucleoli. Within the cytoplasm of some of the tumor cells are eosinophilic inclusions that on ultrastructural examination are seen to be composed of intermediate filaments. Fine-needle aspiration biopsy (FNAB) is an extremely effective technique for diagnosing a variety of benign and
’
Received December 7, 1989. Accepted June 1 1 , 1990. From the Departments of Pathology and Laboratory Medicine and Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Address reprint requests to Mohammed Akhtar, M.D., F.C.A.P., Department of Pathology, King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh 1121 1, Saudi Arabia.
36
Diagnostic Cytopathology, Vol 7, No I
malignant neoplasms in infants and children,4 and detailed studies on FNAB diagnosis of Wilms’ tumor and clear-cell sarcoma have been published. &’ Aspiration biopsy has also been used to diagnose MRTK;4,8however, the morphologic spectrum of diagnostic features exhibited by aspiration smears from this tumor has not yet been established. This article reviews our findings from a series of FNABs in three patients with histologically proven MRTK.
Materials and Methods We reviewed the aspiration smears from six FNABs performed on three patients with MRTK. Histologic examination of the primary and/or metastatic tumor confirmed the FNAB diagnosis in all cases (Table I). Histologic sections and electron micrographs from these cases were also reviewed to establish cytologic, histologic, and ultrastructural correlations. FNABs were performed in the usual manner, and smears were dried and stained with Diff-Quik. For electron microscopic examination, part of the aspirate was fixed in 3 % buffered glutaraldehyde and processed according to our previously described procedure. Tissue from surgically resected specimens was fixed in 10% buffered formaldehyde solution and embedded in paraffin. Three-micron-thick sections were stained by hematoxylineosin (H&E).
Results The cytologic and histopathologic findings can be seen in Figures C-1-C-6.
Cytologic Findings Round to polygonal cells arranged in irregularly shaped clusters were seen on all FNAB smears (Figs. C-1A and C-2A). Several single cells were also present. Some of the @ 1991
WILEY-LISS, INC.
Fig. C-1A
Fig. C-1B
Fig. C-2A
Fig. C-3
Fig. C-4
Fig. C-5
Fig. C-6
Fig. C-2B
Figs. C-1-C-6. Fig. C-1. (A) MRTK aspiration smear featuring variably siLed clusters of tumor cells (Diff-Quik stain, original magnification X 100). (B) Histopathologic section from MRTK showing sheets and clusters of tumor cells with hyalinized areas within the cytoplasm (H&E, original magnification x 100). Fig. C-2. (A) Higher magnification of an aspiration smear from MRTK featuring a cluster of tumor cells containing large vesicular nuclei and basophilic, somewhat granular, cytoplasm (Diff-Quik stain, original magnification X 200). (B) Photomicrograph showing MRTK with a trabecular pattern and markedly dense collagenous stroma (H&E, original magnification x 200). Fig. C-3. Aspiration smear featuring scattered tumor cells. One of the cells reveals a long broad cytoplasmic process (Diff-Quik stain, original magnification X200). Fig. (2-4. Aspiration smear showing a cluster of tumor cells with light purple cytoplasmic inclusions (Diff-Quik stain, original magnification X 250). Fig. C-5. Histopathology showing several tumor cells with hyalinized eosinophilic inclusions (H&E, original magnification X 250). Fig. C-6. Aspiration smear featuring a cell from MRTK containing a cytoplasmic inclusion (Diff-Quik stain, original magnification X 250).
AKHTAR ET AL. Table I. Clinicopathologic Features of Three Patients With MRTK Case number
Aae
Sex
Site of FNAB
1
1 mo
F
2
2 mo
M
3
9 yr
M
Right subscapular region Left kidney Right lobe of liver Right thigh Gum Right kidney
Electron microscopy Surgieal resection Yes
Right nephrectom y
Yes Yes No No
Exenteration of left eye globe containing metastatic MRTK Right nephrectomy; left lower lobe of lung containing metastatic MRTK
Yes
cells were irregular in outline and had broad cytoplasmic processes (Fig. C-3). The nuclei varied from round to slightly irregular and exhibited a reticular arrangement of chromatin and one or more well-developed eosinophilic nucleoli. The cytoplasm stained pale to deep blue and was somewhat granular. Some of the tumor cells had intracytoplasmic inclusions that stained light pink to purple and varied from round to irregular in shape (Figs. C-4 and C-6).
Histopa thologic Features The histopathologic appearance of the tumor was similar for all three cases. The tumors were composed of loosely arranged sheets and clusters of uniform tumor cells with a moderate amount of eosinophilic cytoplasm (Figs. C- lB, C-2B, and C-5). There were round to irregularly shaped hyaline eosinophilic inclusions within some of the tumor cells. The vesicular nuclei were relatively large and eccentrically placed, and they were round to somewhat irregular and indented and usually contained one, or rarely two, prominent well-developed eosinophilic nucleoli. Frequent mitoses were present. A diffuse growth pattern was identified in most of the areas. In some sections, there was a trabecular arrangement of cells with marked stromal hyalinization (Fig. C-2B).
Ultrastructural Features The tumor cells were arranged in variably sized clusters as well as disposed singly (Fig. 1). The cell outlines were irregular, and there were occasional cell junctions. The cytoplasm was moderate in amount and contained clusters of mitochondria, occasional profiles of rough endoplasmic reticulum, and occasional lysosomes. Many of the tumor cells contained variably sized aggregates of 1 0-nm cytoplasmic filaments (Figs. 2 and 3). Some of these aggregates contained trapped cell organelles such as mitochondria and lipid vacuoles. The nuclei were relatively large with 38
Diagnostic Cytopathology, Vol 7, No I
Fig. 1. Electron micrograph depicting a small cluster of tumor cells in which the nuclei are large and nucleoli are prominent. The tumor cells have irregular outlines and contain moderate amounts of cytoplasm (uranyl acetate-lead citrate stain, X 4,000).
moderately irregular outlines. The chromatin was arranged as a thin rim along the nuclear membrane, and usually there was a single well-developed nucleolus. The extracellular matrix contained bundles of normal collagen fibers.
Discussion The histologic diagnosis of MRTK primarily depends on the demonstration of round to polygonal cells containing large vesicular nuclei and prominent nucleoli. Furthermore, a variable number of tumor cells contain eosinophilic cytoplasmic inclusions. All of these morphologic features may be seen in FNAB smears, thus providing a reasonable basis for a morphologic diagnosis. In our experience, however, the cytoplasmic inclusions in the FNAB smears tend to be relatively infrequent and less precise and may thus be difficult to recognize. In view of this, we believe that FNAB diagnosis of MRTK should be confirmed by additional studies such as immunohistochemical and ultrastructural examinations. In our study, electron microscopy confirmed the diagnosis of MRTK in all three cases by demonstrating filamentous cytoplasmic aggregates. Immunoperoxidase staining of the tumor cells
MALIGNANT RHABDOID KIDNEY TUMOR
Fig. 2. Electron micrograph featuring a tumor cell with a large nucleus containing a well-developed nucleolus. The cytoplasm has a few organelles and a prominent filamentous inclusion (uranyl acetate-lead citrate stain, X 6,000).
may also be used to highlight the cytoplasmic inclusions that stain intensely for vimentin and in some cases also for cytokeratin and desmin. lo The differential diagnosis of MRTK primarily includes Wilms' tumor and clear-cell sarcoma of the kidney. FNAB smears from Wilms' tumor usually exhibit undifferentiated, small (blastemal) cells with an admixture of larger pale (epithelial) cells. Variable degrees of tubular differentiation may also be seen. Aspiration smears obtained from cases of MRTK do not possess these features. The typical appearance of clear-cell sarcoma of the kidney consists of polygonal to spindle-shaped cells loosely arranged against a background of pale-staining mucoid material. Rhabdoid tumor usually lacks spindle-shaped cells as well as mucoid intercellular material. In a recent study, Weeks et al. reviewed the morphologic features in a series of 111 cases of MRTK and described the large variety of histologic patterns that may be encountered. lo These patterns include classic, sclerosing, epithelioid, spindle, lymphomatoid, vascular, pseudopapillary, and cystic. The classic pattern was seen in all of our cases. Malignant rhabdoid tumor was initially thought to possess morphologic features indicative of myogenic differ-
'
Fig. 3. Another tumor cell containing a filamentous inclusion in which a lipid vacuole is enclosed (uranyl acetate-lead citrate stain, X 11,600).
'
entiation. However, subsequent studies failed to confirm this and instead generated a multitude of theories concerning its cell of origin. The proposed histogenesis includes histiocytic, epithelial, primitive neurorectodermal, primitive mesenchymal, and multipotential cells of the renal medulla. 'Orz3 Large numbers of immunohistochemical studies have yielded conflicting results. The most consistent finding has been staining of the cytoplasm and cytoplasmic inclusions of the tumor cells for vimentin, whereas cytokeratin and epithelial membrane antigen have been found in some tumors but not in others. Most studies have reported negative staining for desmin; however, a few recent studies have reported its presence. 'Ovz8 Ultrastructurally, the tumor cells reveal frequent intercellular junctions, aggregates of approximately 10-nm intermediate cytoplasmic filaments, and, in some cases, focal basal lamina. 2,3,10-26 No study has presented conclusive evidence for any specific histogenetic origin of the tumor, and there appears to be dual expression of features indicative of mesenchymal and epithelial differentiation, indicating an origin from primitive cells that retain the capacity to differentiate into both epithelial and mesenchymal cells. Malignant rhabdoid tumor, when originally described in 1978, was considered unique to the kidneys of infants Diagnostic Cytoputhology, Vol 7, No I
39
AKHTAR ET AL.
and children. In subsequent years, however, tumors with identical morphologic appearance were reported in a variety of different locations, including soft tissue, central nervous system, pelvis, vulva, prostate, heart, urinary bladder, skin, thymus, and liver. 1-26 These extrarenal malignant rhabdoid tumors were encountered in infants and children and in adults. It is not clear whether the renal and extrarenal malignant rhabdoid tumor is bound by common histogenesis into a specific neoplastic entity or merely represents a heterogeneous group of tumors with overlapping morphologic features and the presence of “rhabdoid” cells. To the best of our knowledge, FNAB diagnosis of extrarenal malignant rhabdoid tumor has not been described. The exact role of FNAB in the diagnosis of renal masses in infants and children remains to be determined. Because nephrectomy is the usual treatment for a renal mass, preoperative diagnosis of the renal mass may not be crucial, regardless of exact histologic destinations. In our experience, however, a preoperative FNAB diagnosis of abdominal and flank masses frequently facilitates the planning of therapy and precludes extensive radiologic and laboratory assessment of the patient, thus minimizing the hospital stay (unpublished data). In addition, in those cases where the tumor is too advanced for immediate surgical resection, FNAB diagnosis may be helpful in outlining the appropriate chemotherapy or radiation therapy so that the tumor may be resected at a later date. The most consistent and noncontroversial use of FNABs, however, is in the diagnosis of metastatic or recurrent tumors in patients with known MRTK and other renal tumors. FNAB in these cases may eliminate the need for a surgical procedure.
’
References 1. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilms’ tumor: results of the first National Wilms’ tumor study. Cancer 1978;41:193748. 2. Haas JE, Palmer NF, Wienberg AG, Beckwith JB. Ultrastructure of malignant rhabdoid tumor of the kidney. Hum Pathol 1981;12: 646-57. 3. Beckwith JB. Wilms’ tumor and other renal tumors of childhood: a selective review from the National Wilms’ tumor study: Pathology Center. Hum Pathol 1983;14:481-92. 4. Akhtar M, Ali MA, Sabbah R, Bakry M, Nash JE. Fine-needle aspiration biopsy diagnosis of round cell malignant tumors of childhood. A combined light a d electron microscopic approach. Cancer 1985;55:1805-17. 5. Akhtar M, Ali MA, Sackey K, Sabbah R, Bakry M. Fine needle aspiration biopsy of clear cell sarcoma of the kidney. Light and electron microscopic correlations. Diagn Cytopathol 1989;5:181-5. 6. Quijano G, Drut R. Cytologic characteristics of Wilm’s tumors in fine-needle aspirates. A study of ten cases. Acta Cytol 1989;23: 263-6.
40
Diagnostic Cytopaihology, Vol 7, No I
7. Akhtar M, Ali MA, Sackey K, Sabbah R, Burgess A. Aspiration cytology of Wilms’ tumor. Diagn Cytopathol 1989;5:269-74. 8. Wakely PE, Giacomantonio M. Fine needle aspiration cytology of metastatic malignant rhabdoid tumor. Acta Cytol 1986;30:533-7. 9. Akhtar M, Bakry M, Nash EJ. An improved technique for processing aspiration biopsy for electron microscopy. Am J Clin Pathol 1986:5 7-60. 10. Weeks DA, Beckwith JB, Meirau GA, Luckey DW. Rhabdoid tumor of the kidney: a report of 11 1 cases from the National Wilms’ Tumor Pathology Center. Am J Surg Pathol 1989;13:439-58. 11. Biggs PJ, Garen PD, Powers J, Garvin AJ. Malignant rhabdoid tumor of the central nervous system. Hum Pathol 1987; 18:332-7. 12. Lynch HT, Shurin SB, Dhams BB, Izant RJ, Lynch J, Danes S. Paravertebral malignant rhabdoid tumor in infancy: in-vitro studies of a familial tumor. Cancer 1983;52:290-6. 13. Small EJ, Gordon GJ, Dahms BB. Malignant rhabdoid tumor of the heart in an infant. Cancer 1985;55:2850-3. 14. Dervan PA, Cahalane SF, Kneafsey P, Mynes A, Mcallister K. Malignant rhabdoid tumor of soft tissue. An ultrastructural and immunohistological study of a pelvic tumor. Histopathology 1987; 1 1:183-90. 15. Parham DM, Peiper SC, Robicheaux G, Ribeiro PC, Douglass EC. Malignant rhabdoid tumor of the liver: evidence for epithelial differentiation. Arch Pathol Lab Med 1988; lI2:614. 16. Gonzales-Crussi F, Goldschmidt RA, Hsueh W, Trujillo YP. Infantile sarcoma with intracytoplasmic filamentous inclusions: distinctive tumor of possible histiocytic origin. Cancer 1982;49:2365-75. 17. Dabbs DJ, Park HK. Malignant rhabdoid skin tumor: An uncommon primary skin neoplasm: ultrastructural and immunohistochemical analysis. J Cutan Pathol 1988;15:109-15. 18. Harris M, Eyden BP, Joglekar VM. Rhabdoid tumor of the bladder: a histological, ultrastructural and immunohistochemical study. Histopathology 1987;11:1083-92. 19. Kent AL, Mahoney DH, Gresik MV, Steuber CP, Fernbach DJ. Malignant rhabdoid tumor of the extremity. Cancer 1987;60: 1056-9. 20. Lemos LB, Hamoudi AB. Malignant thymic tumor in an infant (malignant histiocytoma). Arch Pathol Lab Med 1978;1 0 2 2 6 9 . 21. Ekfors TO, Aho HJ, Ketomaki M. Malignant rhabdoid tumor of the prostatic region: immunohistochemical and ultrastructural evidence for epithelial origin. Virchows Arch [A] 1985;406:381-8. 22. Carter RL, McCarthy KP, Al-Sam SZ, Monaghan P, Agrawal M, McElwain TJ. Malignant rhabdoid tumor of the bladder with immunohistochemical and ultrastructural evidence suggesting histiocytic origin. Histopathology 1989;14:179-90. 23. Seo IS, Min KW, Brodhecker C, MirKin LD. Malignant renal rhabdoid tumor. Immunohistochemical and ultrastructural studies. Histopathology 1988;13:657-66. 24. Tsuneyoshi M, Daimaru Y, Hashimoto H, Enjoji M. Malignant soft tissue neoplasms with the histologic features of renal rhabdoid tumors. Hum Pathol 1985;16:123542. 25. Sotelo-Avila C, Gonzales-Crussi F, de Mello D, et al. Renal and extrarenal rhabdoid tumors in children: a clinicopathologic study of 14 patients. Semin Diagn Pathol 1986;3:151-63. 26. Tsuneyoshi M, Daimaru Y, Hashimoto H, Enjoji M. Malignant soft tissue neoplasms with the histologic features of renal rhabdoid tumors. Hum Pathol 1985;16:123542. 27. Vogel AM, Gown AM, Caughlan J, Haas JE, Beckwith JB. Rhabdoid tumor of the kidney contain mesenchymal specific and epithelial specific intermediate filament proteins. Lab Invest 1984;50:232-8. 28. Tsokos M, Kourklis G, Chandra R, Bhagavan B, Triche JJ. Rhabdoid tumor of the kidney: evidence for epithelial and myogenous differentiation. Lab Invest 1987;56:57P.
A series of six fine-needle aspiration biopsiesfrom three patients with malignant rhabdoid tumor of the kidney is reviewed. The smears revealed round, polygonal, and irregularly shaped cells with large nuclei andprominent nucleoli. Some of the tumor cells contained light pink to purple cytoplasmic inclusions that correlated with the eosinophilic inclusions seen in histopathologic sections and filamentous cytoplasmic aggregates noted on ultrastructural examination. Diagnosis of malignant rhabdoid tumor of the kidney may be suggested from aspiration biopsy smears; however, further conJrmation of the diagnosis by histologic or ultrastructural examination is desirable. Diagn Cytopathol 1991; 7:36-40.
Key Words: Rhabdoid tumor; Kidney; Fine-needle aspiration; Biopsy; Filamentous inclusions
Malignant rhabdoid tumor of the kidney (MRTK) was characterized by Beckwith and Palmer in 1978 as a highly aggressive variant of Wilms’ tumor, but it was later recognized as a separate entity. 2,3 MRTK presents clinically as an abdominal or flank mass that is indistinguishable from Wilms’ tumor and other renal neoplasms encountered in infants and children. Histologically, the tumor is composed of cells arranged in a sheet-like fashion and characterized by a moderate amount of eosinophilic cytoplasm and large vesicular nuclei with prominent nucleoli. Within the cytoplasm of some of the tumor cells are eosinophilic inclusions that on ultrastructural examination are seen to be composed of intermediate filaments. Fine-needle aspiration biopsy (FNAB) is an extremely effective technique for diagnosing a variety of benign and
’
Received December 7, 1989. Accepted June 1 1 , 1990. From the Departments of Pathology and Laboratory Medicine and Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Address reprint requests to Mohammed Akhtar, M.D., F.C.A.P., Department of Pathology, King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh 1121 1, Saudi Arabia.
36
Diagnostic Cytopathology, Vol 7, No I
malignant neoplasms in infants and children,4 and detailed studies on FNAB diagnosis of Wilms’ tumor and clear-cell sarcoma have been published. &’ Aspiration biopsy has also been used to diagnose MRTK;4,8however, the morphologic spectrum of diagnostic features exhibited by aspiration smears from this tumor has not yet been established. This article reviews our findings from a series of FNABs in three patients with histologically proven MRTK.
Materials and Methods We reviewed the aspiration smears from six FNABs performed on three patients with MRTK. Histologic examination of the primary and/or metastatic tumor confirmed the FNAB diagnosis in all cases (Table I). Histologic sections and electron micrographs from these cases were also reviewed to establish cytologic, histologic, and ultrastructural correlations. FNABs were performed in the usual manner, and smears were dried and stained with Diff-Quik. For electron microscopic examination, part of the aspirate was fixed in 3 % buffered glutaraldehyde and processed according to our previously described procedure. Tissue from surgically resected specimens was fixed in 10% buffered formaldehyde solution and embedded in paraffin. Three-micron-thick sections were stained by hematoxylineosin (H&E).
Results The cytologic and histopathologic findings can be seen in Figures C-1-C-6.
Cytologic Findings Round to polygonal cells arranged in irregularly shaped clusters were seen on all FNAB smears (Figs. C-1A and C-2A). Several single cells were also present. Some of the @ 1991
WILEY-LISS, INC.
Fig. C-1A
Fig. C-1B
Fig. C-2A
Fig. C-3
Fig. C-4
Fig. C-5
Fig. C-6
Fig. C-2B
Figs. C-1-C-6. Fig. C-1. (A) MRTK aspiration smear featuring variably siLed clusters of tumor cells (Diff-Quik stain, original magnification X 100). (B) Histopathologic section from MRTK showing sheets and clusters of tumor cells with hyalinized areas within the cytoplasm (H&E, original magnification x 100). Fig. C-2. (A) Higher magnification of an aspiration smear from MRTK featuring a cluster of tumor cells containing large vesicular nuclei and basophilic, somewhat granular, cytoplasm (Diff-Quik stain, original magnification X 200). (B) Photomicrograph showing MRTK with a trabecular pattern and markedly dense collagenous stroma (H&E, original magnification x 200). Fig. C-3. Aspiration smear featuring scattered tumor cells. One of the cells reveals a long broad cytoplasmic process (Diff-Quik stain, original magnification X200). Fig. (2-4. Aspiration smear showing a cluster of tumor cells with light purple cytoplasmic inclusions (Diff-Quik stain, original magnification X 250). Fig. C-5. Histopathology showing several tumor cells with hyalinized eosinophilic inclusions (H&E, original magnification X 250). Fig. C-6. Aspiration smear featuring a cell from MRTK containing a cytoplasmic inclusion (Diff-Quik stain, original magnification X 250).
AKHTAR ET AL. Table I. Clinicopathologic Features of Three Patients With MRTK Case number
Aae
Sex
Site of FNAB
1
1 mo
F
2
2 mo
M
3
9 yr
M
Right subscapular region Left kidney Right lobe of liver Right thigh Gum Right kidney
Electron microscopy Surgieal resection Yes
Right nephrectom y
Yes Yes No No
Exenteration of left eye globe containing metastatic MRTK Right nephrectomy; left lower lobe of lung containing metastatic MRTK
Yes
cells were irregular in outline and had broad cytoplasmic processes (Fig. C-3). The nuclei varied from round to slightly irregular and exhibited a reticular arrangement of chromatin and one or more well-developed eosinophilic nucleoli. The cytoplasm stained pale to deep blue and was somewhat granular. Some of the tumor cells had intracytoplasmic inclusions that stained light pink to purple and varied from round to irregular in shape (Figs. C-4 and C-6).
Histopa thologic Features The histopathologic appearance of the tumor was similar for all three cases. The tumors were composed of loosely arranged sheets and clusters of uniform tumor cells with a moderate amount of eosinophilic cytoplasm (Figs. C- lB, C-2B, and C-5). There were round to irregularly shaped hyaline eosinophilic inclusions within some of the tumor cells. The vesicular nuclei were relatively large and eccentrically placed, and they were round to somewhat irregular and indented and usually contained one, or rarely two, prominent well-developed eosinophilic nucleoli. Frequent mitoses were present. A diffuse growth pattern was identified in most of the areas. In some sections, there was a trabecular arrangement of cells with marked stromal hyalinization (Fig. C-2B).
Ultrastructural Features The tumor cells were arranged in variably sized clusters as well as disposed singly (Fig. 1). The cell outlines were irregular, and there were occasional cell junctions. The cytoplasm was moderate in amount and contained clusters of mitochondria, occasional profiles of rough endoplasmic reticulum, and occasional lysosomes. Many of the tumor cells contained variably sized aggregates of 1 0-nm cytoplasmic filaments (Figs. 2 and 3). Some of these aggregates contained trapped cell organelles such as mitochondria and lipid vacuoles. The nuclei were relatively large with 38
Diagnostic Cytopathology, Vol 7, No I
Fig. 1. Electron micrograph depicting a small cluster of tumor cells in which the nuclei are large and nucleoli are prominent. The tumor cells have irregular outlines and contain moderate amounts of cytoplasm (uranyl acetate-lead citrate stain, X 4,000).
moderately irregular outlines. The chromatin was arranged as a thin rim along the nuclear membrane, and usually there was a single well-developed nucleolus. The extracellular matrix contained bundles of normal collagen fibers.
Discussion The histologic diagnosis of MRTK primarily depends on the demonstration of round to polygonal cells containing large vesicular nuclei and prominent nucleoli. Furthermore, a variable number of tumor cells contain eosinophilic cytoplasmic inclusions. All of these morphologic features may be seen in FNAB smears, thus providing a reasonable basis for a morphologic diagnosis. In our experience, however, the cytoplasmic inclusions in the FNAB smears tend to be relatively infrequent and less precise and may thus be difficult to recognize. In view of this, we believe that FNAB diagnosis of MRTK should be confirmed by additional studies such as immunohistochemical and ultrastructural examinations. In our study, electron microscopy confirmed the diagnosis of MRTK in all three cases by demonstrating filamentous cytoplasmic aggregates. Immunoperoxidase staining of the tumor cells
MALIGNANT RHABDOID KIDNEY TUMOR
Fig. 2. Electron micrograph featuring a tumor cell with a large nucleus containing a well-developed nucleolus. The cytoplasm has a few organelles and a prominent filamentous inclusion (uranyl acetate-lead citrate stain, X 6,000).
may also be used to highlight the cytoplasmic inclusions that stain intensely for vimentin and in some cases also for cytokeratin and desmin. lo The differential diagnosis of MRTK primarily includes Wilms' tumor and clear-cell sarcoma of the kidney. FNAB smears from Wilms' tumor usually exhibit undifferentiated, small (blastemal) cells with an admixture of larger pale (epithelial) cells. Variable degrees of tubular differentiation may also be seen. Aspiration smears obtained from cases of MRTK do not possess these features. The typical appearance of clear-cell sarcoma of the kidney consists of polygonal to spindle-shaped cells loosely arranged against a background of pale-staining mucoid material. Rhabdoid tumor usually lacks spindle-shaped cells as well as mucoid intercellular material. In a recent study, Weeks et al. reviewed the morphologic features in a series of 111 cases of MRTK and described the large variety of histologic patterns that may be encountered. lo These patterns include classic, sclerosing, epithelioid, spindle, lymphomatoid, vascular, pseudopapillary, and cystic. The classic pattern was seen in all of our cases. Malignant rhabdoid tumor was initially thought to possess morphologic features indicative of myogenic differ-
'
Fig. 3. Another tumor cell containing a filamentous inclusion in which a lipid vacuole is enclosed (uranyl acetate-lead citrate stain, X 11,600).
'
entiation. However, subsequent studies failed to confirm this and instead generated a multitude of theories concerning its cell of origin. The proposed histogenesis includes histiocytic, epithelial, primitive neurorectodermal, primitive mesenchymal, and multipotential cells of the renal medulla. 'Orz3 Large numbers of immunohistochemical studies have yielded conflicting results. The most consistent finding has been staining of the cytoplasm and cytoplasmic inclusions of the tumor cells for vimentin, whereas cytokeratin and epithelial membrane antigen have been found in some tumors but not in others. Most studies have reported negative staining for desmin; however, a few recent studies have reported its presence. 'Ovz8 Ultrastructurally, the tumor cells reveal frequent intercellular junctions, aggregates of approximately 10-nm intermediate cytoplasmic filaments, and, in some cases, focal basal lamina. 2,3,10-26 No study has presented conclusive evidence for any specific histogenetic origin of the tumor, and there appears to be dual expression of features indicative of mesenchymal and epithelial differentiation, indicating an origin from primitive cells that retain the capacity to differentiate into both epithelial and mesenchymal cells. Malignant rhabdoid tumor, when originally described in 1978, was considered unique to the kidneys of infants Diagnostic Cytoputhology, Vol 7, No I
39
AKHTAR ET AL.
and children. In subsequent years, however, tumors with identical morphologic appearance were reported in a variety of different locations, including soft tissue, central nervous system, pelvis, vulva, prostate, heart, urinary bladder, skin, thymus, and liver. 1-26 These extrarenal malignant rhabdoid tumors were encountered in infants and children and in adults. It is not clear whether the renal and extrarenal malignant rhabdoid tumor is bound by common histogenesis into a specific neoplastic entity or merely represents a heterogeneous group of tumors with overlapping morphologic features and the presence of “rhabdoid” cells. To the best of our knowledge, FNAB diagnosis of extrarenal malignant rhabdoid tumor has not been described. The exact role of FNAB in the diagnosis of renal masses in infants and children remains to be determined. Because nephrectomy is the usual treatment for a renal mass, preoperative diagnosis of the renal mass may not be crucial, regardless of exact histologic destinations. In our experience, however, a preoperative FNAB diagnosis of abdominal and flank masses frequently facilitates the planning of therapy and precludes extensive radiologic and laboratory assessment of the patient, thus minimizing the hospital stay (unpublished data). In addition, in those cases where the tumor is too advanced for immediate surgical resection, FNAB diagnosis may be helpful in outlining the appropriate chemotherapy or radiation therapy so that the tumor may be resected at a later date. The most consistent and noncontroversial use of FNABs, however, is in the diagnosis of metastatic or recurrent tumors in patients with known MRTK and other renal tumors. FNAB in these cases may eliminate the need for a surgical procedure.
’
References 1. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilms’ tumor: results of the first National Wilms’ tumor study. Cancer 1978;41:193748. 2. Haas JE, Palmer NF, Wienberg AG, Beckwith JB. Ultrastructure of malignant rhabdoid tumor of the kidney. Hum Pathol 1981;12: 646-57. 3. Beckwith JB. Wilms’ tumor and other renal tumors of childhood: a selective review from the National Wilms’ tumor study: Pathology Center. Hum Pathol 1983;14:481-92. 4. Akhtar M, Ali MA, Sabbah R, Bakry M, Nash JE. Fine-needle aspiration biopsy diagnosis of round cell malignant tumors of childhood. A combined light a d electron microscopic approach. Cancer 1985;55:1805-17. 5. Akhtar M, Ali MA, Sackey K, Sabbah R, Bakry M. Fine needle aspiration biopsy of clear cell sarcoma of the kidney. Light and electron microscopic correlations. Diagn Cytopathol 1989;5:181-5. 6. Quijano G, Drut R. Cytologic characteristics of Wilm’s tumors in fine-needle aspirates. A study of ten cases. Acta Cytol 1989;23: 263-6.
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Diagnostic Cytopaihology, Vol 7, No I
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