College of American Pathologists
CAP Committees & Leadership CAP Calendar of Events Estore CAP Media Center CAP Foundation
 
About CAP    Career Center    Contact Us      
Search: Search
  [Advanced Search]  
 
CAP Home CAP Advocacy CAP Reference Resources and Publications CAP Education Programs CAP Accreditation and Laboratory Improvement CAP Members
CAP Home > Case of the Month > December 2008 - Kidney > Case Critique
Printable Version

2008 — December Case of the Month

Updated December 16, 2008

CLINICAL SUMMARY: KIDNEY  

CAP Foundation December 2008 Online Case of the Month

View case with:
PC users: ImageScope
First-time use of ImageScope?
* Download (required)

Why use ImageScope?

ImageScope offers many additional features including:

• Ability to view multiple slides
  concurrently; synchronize
  panning/zooming.

• Facility to author annotations.

• Capability to run analysis
  algorithms, and display results.

• Modify image brightness,
  contrast, color balance,
  etc.

• Generally faster and more
  responsive.

MAC/PC Users: WebViewer

After reading the summary, try answering the three related multiple-choice questions below.

A 57-year-old woman presented with hematuria. Radiographic studies revealed a left renal mass, and a radical nephrectomy was performed. The enlarged kidney was almost entirely replaced by an ovoid, 14.5 cm long, 8.5 cm diameter, firm tumor having a lobulated, pale gray-tan cut surface with areas of yellow-green necrosis. There was no gross evidence of vascular invasion or of renal pelvic extension. The tumor cells were smooth muscle actin (+) and cytokeratin (-).

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2005, Case 05 and is a leiomyosarcoma.

Criteria for Diagnosis and Comments:
This spindle cell neoplasm of the kidney shows the morphology of a smooth muscle tumor. It has a circumscribed border with the adjacent renal parenchyma and is composed of alternating cellular fascicles of spindle cells with blunt-ended, non-tapering nuclei and eosinophilic cytoplasm. There is variable, frequently marked pleomorphism, including multinucleated tumor giant cells. The presence of mitoses, including atypical forms, and foci of tumor necrosis further characterize this tumor as a high grade leiomyosarcoma.

Leiomyosarcoma (LMS) of the kidney is a rare lesion, comprising only 0.5% of all primary renal malignancies. However, among renal sarcomas LMS accounts for 50-60% of cases. Most occur in adults, and patients usually present with flank pain, hematuria and a mass. Tumors are usually large, solid, gray-white, soft to firm and focally necrotic. They may arise from the renal capsule, renal parenchyma, pelvic muscularis, or the main renal vein.

The cells of low grade lesions typically resemble those of nonneoplastic smooth muscle. High grade lesions are pleomorphic and can appear undifferentiated, requiring immunohistochemical stains to separate them from other sarcomas, the more common being sarcomatoid renal cell carcinoma (RCC) and from atypical forms of angiomyolipoma (AML). LMS typically expresses smooth muscle actin, desmin, calponin and h-caldesmon and are negative for cytokeratin (AE1/AE3), S100 protein, and HMB-45.

LMS of the kidney is an aggressive tumor with a 5-year survival rate of 29-36%; most patients die of disease within 1 year of diagnosis. Small size (<5 cm), low histologic grade, and renal-limited disease are associated with the most favorable outcome.

The presence of necrosis, nuclear pleomorphism and more than a rare mitotic figure distinguish LMS from leiomyoma, which is typically encountered in adults as incidental, small (millimeter-sized) capsular tumors at autopsy. Rarely, leiomyomas are large (up to 37 kg) and may have calcification and cystic change, but necrosis should not be present. In addition to staining for actin and desmin, some capsular leiomyomas focally express HMB-45, suggesting a relationship to AML and other tumors derived from the perivascular epithelioid cell.

AML is composed of an admixture of adipose tissue, abnormal blood vessels and variably differentiated smooth muscle. In most instances, its distinctive and familiar histology allows for a straightforward diagnosis. Histologic variation in the components of AML can, however, lead to an error in diagnosis, particularly if the tumor is not well sampled, and differentiation from other tumors is necessary when the relative proportion of the three components becomes extreme or any of the components shows pleomorphism.

The perivascular cells represent the "myo" portion of AML, show the most variable histology and most frequently appear as spindle cells and rounded epithelioid cells with variable atypia. In addition, many lesions have immature muscle cells, including leiomyoblasts. The presence of nuclear pleomorphism and mitotic activity in AML is not evidence of malignancy. Only rare cases of true sarcomatous transformation (usually high grade leiomyosarcoma) with pulmonary metastases have been reported. Excluding the monotypic epithelioid variant which may have malignant potential with a risk for invasion and metastasis, AML can be regarded as a benign mesenchymal neoplasm. Furthermore, the presence in regional lymph nodes, extension into the renal vein/vena cava, or involvement of perirenal tissue is not indicative of malignant progression.

In cases where leiomyosarcoma is a diagnostic consideration, the identification of "arterialized" veins or the presences of perivascular collarettes and "hair-on-end" myocytes can be helpful in making the correct diagnosis of AML. In addition, AML has a unique immunophenotype. It not only expresses smooth muscle markers (muscle-specific actin, smooth muscle actin, calponin and desmin [50% of cases]) but is also immunoreactive for both melanosome and melanoma markers (HMB-45, HMB-50, CD63 and Melan-A [MART-1]). AML is consistently negative for epithelial antigens (cytokeratins and EMA).

Sarcomatoid RCC should always be included in the differentiated diagnosis of a malignant spindle cell neoplasm of the kidney. It is not a distinct histologic subtype of RCC but may arise in any of the four distinct subtypes of adult RCC - conventional (clear cell), papillary (chromophil), chromophobe, and collecting duct carcinoma. Although frequently undifferentiated, the sarcomatoid component can resemble malignant fibrous histiocytoma or fibrosarcoma and contain heterologous elements, including rhabdomyosarcomatous, chondrosarcomatous or osseous differentiation. The sarcomatoid component may predominate, but adequate sampling will generally reveal a carcinomatous element. Tumors composed exclusively of sarcomatoid or spindled elements without a recognizable epithelial component should be categorized as unclassified RCC. The immunoprofile of sarcomatoid RCC is extremely important in that it allows separation of this tumor from other entities that may mimic it. It is immunoreactive for cytokeratin (AE1/AE3) (94% of cases), vimentin (56% of cases), and EMA (50% of cases). Sarcomatoid collecting duct carcinomas may express high molecular weight cytokeratin (34BE12) as well as mark for UEA-1 lectin. A leiomyosarcoma-like histologic appearance in sarcomatoid RCC was not observed in the study by dePeralta-Venturina and colleagues. Therefore, a malignant appearing spindle cell neoplasm with histologic and immunophenotypic smooth muscle features is most likely a leiomyosarcoma or AML.

Both sarcomatoid RCC and sarcomatoid urothelial carcinoma can have similar histologic features and immunophenotype (cytokeratin and vimentin +). Thorough sampling will usually reveal nests of better differentiated invasive urothelial carcinoma or areas characteristic of papillary urothelial carcinoma or urothelial carcinoma in situ. Concurrent glandular, squamous and poorly differentiated histology, desmoplasia, epicenter of the tumor in the pelvicaliceal system, and history of urothelial carcinoma are helpful in this differential diagnosis.

Inflammatory myofibroblastic tumor (IMT) clinically mimics malignancy and should be included in the differential diagnosis of spindle cell tumors of the kidney. Absence of cellular atypia and necrosis and rarity of mitoses help to distinguish IMT from renal LMS with focal myxoid change. Three histologic patterns can be seen in IMTs with one pattern predominating in the majority of tumors: 1) loosely organized spindle cells admixed with small blood vessels and inflammatory cells in a myxoid background, 2) spindle cell proliferation admixed with variable amounts of dense collagen, lymphoid aggregates often forming follicles, and plasma cells, 3) hypocellular fibrous tissue with dense "keloid-like" fibrosis and sparse inflammatory cells. Immunohistochemically there is diffuse positivity for vimentin; smooth muscle actin and muscle specific actin (HHF-35) are positive in the majority of cases (focal or diffuse). Desmin, CD34 and pankeratin have been negative in all cases tested, as was ALK-1 (Kapusta et al.) In studies of non-renal IMT, ALK-1 abnormalities have been reported in 37-60% of cases by immunohistochemistry and FISH, with ALK-1 positive cases in younger patients (children and young adults).

Solitary fibrous tumor is another benign mimic of a renal sarcoma. Cellularity is variable and consists of a proliferation of uniformly bland spindle cells in a haphazard, storiform, short fascicular or hemangiopericytoma-like growth pattern and less cellular dense collagenous bands. Immunostaining for CD34, bcl-2 and CD99 confirms the diagnosis.

Supplementary Questions For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question Diagnostic Set
1. In which tumor can ALK-1 expression be of potential diagnostic value? A. Angiomyolipoma
B. Inflammatory myofibroblastic tumor
C. Leiomyoma
D. Leiomyosarcoma
E. Sarcomatoid renal cell carcinoma
F. Sarcomatoid urothelial carcinoma
G. Solitary fibrous tumor
2. Which malignant-appearing spindle cell neoplasm has histologic and immunophenotypic smooth muscle features and is negative for cytokeratin and HMB-45? A. Angiomyolipoma
B. Inflammatory myofibroblastic tumor
C. Leiomyoma
D. Leiomyosarcoma
E. Sarcomatoid renal cell carcinoma
F. Sarcomatoid urothelial carcinoma
G. Solitary fibrous tumor
3. For which tumor is the presence in regional lymph nodes, renal vein/vena cava extension or involvement of perirenal tissue not indicative of malignant progression? A. Angiomyolipoma
B. Inflammatory myofibroblastic tumor
C. Leiomyoma
D. Leiomyosarcoma
E. Sarcomatoid renal cell carcinoma
F. Sarcomatoid urothelial carcinoma
G. Solitary fibrous tumor

References

  1. Bonsib SM. HMB-45 reactivity in renal leiomyomas and leiomyosarcomas. Mod Pathol. 1996;9:664-669.
  2. Cheville JC, Lohse CM, Zincke H, et al. Sarcomatoid renal cell carcinoma. An examination of underlying histologic subtype and analysis of associations with patient outcome. Am J Surg Pathol. 2004;28:435-441.
  3. Coffin CM, Watterson J, Priest JR, et al. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor): a clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol. 1995;19:859-872.
  4. Coffin CM, Humphrey PA, Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathologic survey. Semin Diagn Pathol. 1998;15:85-101.
  5. Coffin CM, Patel A, Perkins S, et al. ALK1 and p80 expression and chromosomal rearrangements involving 2p23 in inflammatory myofibroblastic tumor. Mod Pathol. 2001;14:569-576.
  6. Cook JR, Dehner LP, Collins MH, et al. Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study. Am J Surg Pathol. 2001;25:1364-1371.
  7. Delong W, Grignon DG, Eberwein P, et al. Sarcomatoid renal cell carcinoma: An immunohistochemical study of 18 cases. Arch Pathol Lab Med. 1993;117:636-640.
  8. DePeralta-Venturina M, Moch H, Amin M, et al. Sarcomatoid differentiation in renal cell carcinoma. A study of 101 cases. Am J Surg Pathol. 2001;25:275-284.
  9. Deyrop AT, Montgomery E, Fisher C. Leiomyosarcoma of the kidney. A clinicopathologic study. Am J Surg Pathol. 2004;28:178-182.
  10. Eble JN. Angiomyolipoma of kidney. Sem Diagn Pathol. 1998;15:21-40.
  11. Eble JN, Sauter G, Epstein JI, Sesterhenn IA (eds). World Health Organization Classification of Tumors: Pathology and Genetics of Tumours of the Urinary System and Male Genital System. IARC Press, Lyon; 2004.
  12. Grignon D, Ayala A, Ro J, et al. Primary sarcomas of the kidney. A clinicopathologic and DNA flow cytometric study of 17 cases. Cancer. 1990;65:1611-1618.
  13. Hayashi T, Tsuda N, Chowdhury PR, et al. Renal angiomyolipoma. Clinicopathologic features and differential diagnosis. J Urol Pathol. 1999;10:121-140.
  14. Kapusta LR, Weiss MA, Ramsay J, et al. Inflammatory myofibroblastic tumors of the kidney. A clinicopathologic and immunohistochemical study of 12 cases. Am J Surg Pathol. 2003;27:658-666.
  15. Magro G, Cavallaro V, Torrisi A, et al. Intrarenal solitary fibrous tumor of the kidney. Report of a case with emphasis on the differential diagnosis in the wide spectrum of monomorphous spindle cell tumors of the kidney. Pathol Res Pract. 2002;198:37-43.
  16. Stone CH, Lee MW, Amin M, et al. Renal angiomyolipoma. Further immunophenotypic characterization of an expanding morphologic spectrum. Arch Pathol Lab Med. 2001;125:751-758.
  17. Wang J, Arber DA, Frankel K, Weiss LM. Large solitary fibrous tumor of the kidney: Report of two cases and review of the literature. Am J Surg Pathol. 200125:1194-1199.
Author:
2005
Mark A. Weiss, M.D.
Surgical Pathology Committee
TriHealth Laboratories, Good Samaritan Hospital
Cincinnati, OH
 
 © 2014 College of American Pathologists. All rights reserved. | Terms and Conditions | CAP ConnectFollow Us on FacebookFollow Us on LinkedInFollow Us on TwitterFollow Us on YouTubeFollow Us on FlickrSubscribe to a CAP RSS Feed