College of American Pathologists
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2009 — September Case of the Month

Updated August 20, 2009


CAP Foundation September 2009 Online Case of the Month

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A 53-year-old woman was involved in a motor vehicle accident. Upon evaluation at the emergency room, a computed tomography (CT) of the abdomen revealed a 7.0 cm mass in the lower pole of the right kidney. The patient had a right nephrectomy. A well-circumscribed tumor measuring 8.0 x 7.0 x 6.5 cm was confined within the kidney extending from the renal cortex to the renal medulla sparing the renal vein. The solid cut surface was grey-white with multiple small hemorrhagic foci.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2006, Case 23 and is a Mucinous tubular and spindle cell carcinoma of kidney (MTSCC).

Criteria for Diagnosis and Comments:

The histological sections of this renal tumor show features characteristic of mucinous tubular and spindle cell carcinoma of kidney (MTSCC), a previously unclassified and rare entity adopted by the World Health Organization (WHO) and incorporated into the classification of renal neoplasms in December 2002. The microscopically circumscribed and unencapsulated tumor is composed of tightly packed and anastomosing cords and elongated and branching tubules. The neoplastic cells are cytologically low-grade and cuboidal in shape with scant clear to pale acidophilic cytoplasm and round central nuclei without conspicuous nucleoli. This epithelial component is interspersed with abrupt transitions into spindle cell arrays, which may have trabecular or sheet-like growth patterns. Tubular or solid growth patterns may also predominate. The epithelial structures are found in a bubbly, myxoid appearing mucinous stroma. Plasma cells, mast cells, or clusters of foamy histiocytes are frequently identified within this stroma. Mitotic activity is minimal and the Fuhrman grade is either 1 or 2.

The tubules of this tumor have characteristically long profiles and a surrounding basal lamina, which may be highlighted with positive PAS staining. The myxoid background has little affinity for mucicarmine but stains extensively for Alcian blue. Staining by immunohistochemistry has marked variation with most consistent reactivity with Vimentin and EMA. Tumors also express various cytokeratins including AE1/3, 34?E12, CK7, CK8, CK18, and CK19. There is noteworthy controversy in the literature with respect to the validity of staining with Ulex europaeus lectin. The MIB-1 index is very low. The most recent literature describes staining with α-methylacyl-CoA-racemase (AMACR), a biomarker initially introduced to discriminate between prostatic adenocarcinoma and benign prostatic glands. Immunoreactivity in MTSCC is observed in both tubular and spindle cells with a cytoplasmic staining pattern that very closely resembles that of papillary RCC.

The gross appearance of MTSCC is typically solitary, well-circumscribed, solid, pale tan to yellow to grey-white and extends from the renal cortex to the renal medulla with small cystic or hemorrhagic foci with or without focal necrosis. It occurs predominantly in females (3:1) with a mean age of 53 years and usually is found incidentally. Rare tumors may exhibit hematuria, flank pain, palpable abdominal mass, or nephrolithiasis. Radiographic findings illustrate a mass protruding from the renal surface and angiography usually corresponds to a hypovascular lesion.

MTSCC is presumed to arise from the collecting ducts, possibly the loop of Henle. In contrast to typical collecting duct carcinomas, however, these tumors behave indolently and typically portend a good prognosis with no tumor-related deaths reported to date. A lack of renal vein, adrenal, and regional lymph node involvement is classic as well as the absence of distant metastases at the time of diagnosis. Surgical resection is usually curative and subsequent recurrence or metastases at follow-up are also exceedingly rare.

The differential diagnosis of MTSCC is broad and is outlined in the following paragraphs. Angiomyolipoma has a very strong association with tuberous sclerosis (TS), and occurs in 80% of patients diagnosed with TS. Less commonly, it is also observed in patients with von Recklinghausen disease, von Hipppel-Lindau syndrome, and autosomal dominant (adult) polycystic kidney disease. Angiomyolipoma, which accounts for up to 2% of all renal tumors, occur predominantly in women at a 2:1 ratio. Angiomyolipomas are well circumscribed and unencapsulated like MTSCC but they are multiple or bilateral in many cases, perhaps due to their association with hereditary diseases. This neoplasm, which originates from the perivascular epithelioid cells, exhibits mature fat, smooth muscle, and vascular components within the neoplastic component of the tumor. The vascular component of the tumor is usually the most striking, composed of vessels with thickened, irregular walls. In cases where the smooth muscle component predominates, separation from MTSCC can be difficult. The MTSCC however is devoid of the other characteristic elements of angiomyolipoma and by contrast, clinically is shown to be hypo- or avascular by angiographic studies. The neoplastic cells of angiomylipoma stain positively for HMB-45 whereas those of MTSCC do not.

Juxtaglomerular cell tumor is a rare neoplasm that differentiates toward the modified smooth muscle cells of the juxtaglomerular apparatus. This tumor occurs over an extremely wide age range, documented in patients between 6 and 69 years. The most common initial presenting sign is hypertension, which may precede tumor diagnosis by several years and is most often secondary to elevated renin levels. The tumors are benign and surgical resection is curative. The gross appearance is very similar to that of MTSCC in that these unifocal tumors, which are found in the renal cortex and usually measure less than 4 cm, are well circumscribed and solid, with a gray-white to yellow parenchyma with hemorrhagic foci. They are composed of cells that may be similar to the tubular component of the MTSCC. These cells are uniform and round with round to oval nuclei and acidophilic cytoplasm and may be arranged in a trabeculated pattern similar to MTSCC. The cells often contain rhomboid-shaped renin granules as an ultrastructural feature. This differs from the neurosecretory granules, which are observed in the cytoplasm of the tumor cells of the MTSCC. These tumors also lack the spindle cell component critical to the diagnosis of MTSCC and are non-reactive to cytokeratins.

Collecting duct carcinoma (CDC) is a rare tumor of the kidney comprising less than 1% of the malignant epithelial renal neoplasms in adults. As its name implies, it originates from collecting ducts, similar to MTSCC. In contrast to MTSCC, this tumor has very infiltrative borders and a multicystic appearance. Histologically it has a predominantly tubular pattern and may exhibit sarcomatoid change, which can be similar to MTSCC. However, CDC is of much higher cytologic grade than MTSCC with its characteristic prominent nucleoli, frequent and occasionally bizarre mitoses, and significant cystic component. Like MTSCC, CDC also stains positively for EMA and CK7 and CK8.

Metanephric adenoma is a tumor derived from metanephric blastema that most commonly occurs in women with a mean age of 41 (range: 5 to 83 years). It has very similar gross features to MTSS, varying in size from 0.3 to 15 cm. They are also well circumscribed but unencapsulated tumors: however the neoplastic cells of metanephric adenoma architecturally form small acini as opposed to the trabecular, tubular, or solid patterns of the MTSCC. The bland oval tumor cells of metanephric adenoma also have basophilic cytoplasm in contrast to the acidophilic cytoplasm of MTSCC; psammoma bodies may be seen in the stroma of metanephric adenoma and are usually absent from MTSCC. Finally, metanephric adenoma is negative for EMA and AE1/AE3 unlike MTSCC.

Renal cell carcinoma with sarcomatoid differentiation possesses marked cytologic atypia and pleomorphism compared to the cytologic appearance of MTSCC, which has monotonous round nuclei with inconspicuous nucleoli and rare mitoses. Since renal cell carcinoma with sarcomatoid differentiation has a generally poor prognosis in contradistinction to MTSCC, it is extremely important to accurately distinguish between these two entities. The staining patterns of both of these carcinomas have extensive overlap including positive staining in both tumor types for α-methylacyl-CoA-racemase (AMACR), CK7, and EMA. Therefore immunohistochemical staining patterns do not eliminate this potential pitfall and the distinction is based on H & E histology.

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
Which tumor possesses rhomboid-shaped renin granules ultrastructurally? A. Angiomyolipoma
B. Collecting duct carcinoma
C. Juxtaglomerular cell tumor
D. Metanephric adenoma
E. Mucinous tubular and spindle cell carcinoma of kidney (MTSCC)
F. Renal cell carcinoma with sarcomatoid differentiation
Which tumor typically expresses HMB-45 in neoplastic cells? A. Angiomyolipoma
B. Collecting duct carcinoma
C. Juxtaglomerular cell tumor
D. Metanephric adenoma
E. Mucinous tubular and spindle cell carcinoma of kidney (MTSCC)
F. Renal cell carcinoma with sarcomatoid differentiation
Which tumor frequently has psammoma bodies in the stroma? A. Angiomyolipoma
B. Collecting duct carcinoma
C. Juxtaglomerular cell tumor
D. Metanephric adenoma
E. Mucinous tubular and spindle cell carcinoma of kidney (MTSCC)
F. Renal cell carcinoma with sarcomatoid differentiation


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Daniel J. Carter, MD
Surgical Pathology Committee
Berkshire Medical Center
Pittsfield, MA

Colleen Ann Murphy, MD
Surgical Pathology Committee
Berkshire Medical Center
Pittsfield, MA