Mucinous tubular and spindle cell carcinoma.

A case of a 30-year-old female patient diagnosed with mucinous tubular and spindle cell carcinoma (MT&SCC) of her left kidney of the basis of an abdominal ultrasound scan performed when nonspecific pain is presented. The histopathology report revealed a classic type of MT&SCC. Photographs of histopathological samples are shown. Nephrectomy was applied as sole treatment. A follow-up of six years confirmed surgery to be a sufficient approach. The discussion presents a review of up to date world literature concerning the histopathological features, prognosis, and treatment of MT&SCC.

INTRODUCTION

Mucinous tubular and spindle cell carcinoma (MT&SCC) is a rare kidney cancer listed in the WHO classification since 2004. Treatment standards for this particular type of cancer have not yet been established. The necessity to differentiate this type of cancer with other types of kidney cancer has been previously stressed [1].

We present a case of a 30-year-old female patient who underwent nephroureterectomy due to a single large tumor of the left kidney.

CASE REPORT

A 30-year old woman reported with an abdominal ultrasound scan performed for nonspecific abdominal pain. The ultrasound revealed the presence of a 62 x 52 mm spherical tumor located in the upper pole of the patient's left kidney. The lesion was solid, hyperechogenic, and well-demarcated. It showed no signs of infiltration of neighboring tissues, but did model the hilum. Within the tumor, a strongly hyperechogenic and a hypoechogenic section were found. No other abnormalities were noted.

A CT scan was performed – the tumor was originally assessed at 40 H.U. and reached 48 H.U. after contrast administration. No signs of disease dissemination were found.

The patient's physical examination, blood morphology, biochemical analysis results, and chest X-ray were normal, and she did not present with hematuria. Her GFR was measured by means of scintigraphy and was found to be 111 ml/min (left kidney 49%, right kidney 51% of total), which was just below the age norm (115 ml/min).

A left nephroureterectomy was performed (in another center). No complications followed the procedure. The pathologist's report was as follows:

On gross examination a pale compact mass measuring 6 x 5 x 4.5 cm was seen towards one of the kidney poles. The mass was found to bulge the fibrous kidney capsule, without obvious capsule breach. No necrosis or hemorrhage was seen in the tumor tissue. The hilum area was not involved. The renal parenchyma beyond the mass appeared normal.

On microscopic examination, sections showed a triphasic tumor containing: 1) spindle-cell areas; 2) tubulo-papillary areas with focal myxoid, edematous stroma; and 3) compact areas of numerous „collapsed” tubules focally embedded in „bubbly” stroma. Tumor cells in all three components showed only minor nuclear atypia and vesicular nuclei with indistinct nucleoli seen only under 400x magnification (as in Fuhrman grade 2). Mitotic activity did not exceed two mitotic figures in 10 high-power fields. There was lymphocytic sprinkling throughout the tumor and focal aggregates of foamy macrophages were seen. There was no evidence of necrosis or angiolymphatic invasion. The tumor was found to infiltrate the fibrous capsule without capsule breach.

Immunostains and histochemistry revealed the tumor cells in all components to express: pan-cytokeratin (CK AE1/3), high-molecular weight cytokeratin (CK HMW [34BE12]), and vimentin. Cytokeratin 7 was only noted in the tubulo-papillary component. CD10 was negative.

In PAS/Alcian Blue staining the „bubbly” stroma was blue, consistent with mucus, and basal laminas of compact tubules were decorated red.

The main differential diagnosis included papillary RCC (pRCC), collecting duct carcinoma, and metanephric adenoma. Papillary RCC rarely shows extracellular mucin and lacks a spindle cell component, unless accompanied by a sarcomatoid change (in which case the spindle cell component shows high-grade features). CD10 antigen is frequently seen in pRCC, but it was negative in our case. Collecting duct carcinoma is an aggressive tumor showing high-grade histology. Metanephric adenoma shows tubulo-papillary architecture, but stromal and spindle cell components are lacking and cytokeratin 7 is usually negative.

The diagnosis of MT&SCC pT1b was established.

A postoperative CT scan and annual abdominal ultrasound scans showed no signs of recurrence. The patient required no additional treatment and remains under observation. During 56 months of follow-up no signs of dissemination were noted, and she has successfully given birth to a healthy child.

DISCUSSION

MT&SCC has been documented to develop at various ages, 33-80 years [1–4; 6, 7, 8]. Shen et al. report a ratio of male:female of 1:3 [8].

Nonspecific abdominal pains are usually reported, and patients may present with hematuria. [3, 3, 5, 11] This was also true of this patient, who has developed a large mass of tumor before any symptoms were noted.

Although MT&SCC has only recently been isolated from RCCs, shown to be a distinct form of cancer usually consisting of elongated, small tubules with cuboidal cells, or cords of spindled cells showing mild atypia, variant forms have already been described. [2, 3; 5–9] It does not express kidney-specific cadherin (Ksp-cad), typical of the ascending loop of Henle cells [10]. Ours is a case of a “classic” MT&SCC.

Immunohistochemistry has a limited role in differential diagnosis of MT&SCC and pRCC. Both tumors show several analogies in morphology and immunoprofile [10] and some authors regarded them as variants of the same entity [12]. Main differences can be found at the level of genetic mutations typical of MT&SCC and pRCC [13, 14], but we did not perform cytogenetic or molecular analysis of the presented case.

As in our case, MT&SCC rarely shows signs of dissemination [8, 11].

A treatment standard for this particular type of cancer has not yet been established.

MT&SCC seems to be associated with good prognosis, unless sarcomatoid lesions are present within the neoplasmatic tissue [1, 5, 6, 7]. Patients with sarcomatoid and disseminated disease have much worse prognosis than those with the classic type, even when large tumors confined to the kidney are discovered [1-8]. The main treatment method up till now remains radical nephrectomy, even in cases of disseminated disease [7, 11]. Usually they do not require adjuvant treatment [1, 11].

Our patient was treated with nephroureterectomy, which up till now seems to have proved sufficient.

CONCLUSIONS

MT&SCC is associated with good prognosis and surgical treatment usually proves sufficient. Careful histopathological examination remains the key to diagnosis and further treatment. As more evidence is gathered, a standard for the treatment should be established.

Spindle cell component of the tumor (x40 magnification), characteristic of MT&SCC.

Tubulo-papillary tumor component (X40 magnification), the second characteristic feature of MT&SCC.

“Bubbly” tumor stroma (x200 magnification), the third distinguishing feature of MT&SCC.

PAS/Alcian Blue staining reveals the blue decoration of the stroma, characteristic of mucus producing neoplasms (x200 magnification).

Pan-cytokeratin expressed (CK AE1/3) in the tubulo-papillary component (x200 magnification).