| Abstract|| |
Urothelial carcinoma of urinary bladder with divergent differentiation into rhabdomyosarcoma (RMS) is an extremely uncommon aggressive phenomenon. We present a case of a 74-year-old male with bladder carcinoma which metastasized to the abdominal wall as epithelioid RMS. To the best knowledge of our literature searches, an oligometastasis of exclusive heterologous component has not been described before. The clinical, radiological, and immunohistochemistry profile of the patient supported the monoclonal nature of the tumor.
Keywords: Metastasis, rhabdomyosarcoma, urothelial carcinoma
|How to cite this article:|
Agarwal P, Pasricha S, Gupta G, Sharma A, Mehta A. Urothelial carcinoma of urinary bladder with exclusive heterologous component of epithelioid rhabdomyosarcoma at metastatic site. Indian J Pathol Microbiol 2018;61:258-60
|How to cite this URL:|
Agarwal P, Pasricha S, Gupta G, Sharma A, Mehta A. Urothelial carcinoma of urinary bladder with exclusive heterologous component of epithelioid rhabdomyosarcoma at metastatic site. Indian J Pathol Microbiol [serial online] 2018 [cited 2020 Jul 2];61:258-60. Available from: http://www.ijpmonline.org/text.asp?2018/61/2/258/230567
| Introduction|| |
Urothelial carcinoma (UC) of urinary bladder is notorious to show divergent differentiation along squamous, small cell, glandular, trophoblastic, and even rhabdoid cell lines., However, rhabdomyosarcomatous differentiation in adult urinary bladder carcinoma is uncommon. This differentiation may be demonstrated in bladder as pure rhabdomyosarcoma (RMS) or as a component of sarcomatoid UC (SUC) with an aggressive course. We discuss a rare case of UC of urinary bladder with an occult heterologous component of ERMS which is seen at the metastatic site as an exclusive component.
| Case Report|| |
A 74-year-old male was investigated for bouts of hematuria over a month. He was a known hypertensive, controlled on medication. He was also an alcoholic and a chronic smoker. The patient had no significant past or family history. A contrast-enhanced computed tomography (CT) scan of abdomen was done which revealed urinary bladder wall thickening involving anterior wall, posterior wall, and dome measuring 5 cm × 4.8 cm × 4.8 cm. Overlying abdominal wall showed a growth measuring 4.8 cm × 4.1 × 3 cm. Findings were suggestive of malignant growth of urinary bladder with enterovesical fistula and anterior abdominal wall metastasis. Positron emission tomography CT did not reveal any other fludeoxyglucose avid lesion elsewhere in the body other than abdominal wall. Bladder biopsy was diagnostic of invasive UC, high grade with muscle invasion and extensive areas of necrosis. An exploratory laparotomy with partial cystectomy and segmental ileal resection with ileo-ileal anastomosis with double-barreled ileostomy was performed along with wide local excision of the abdominal wall metastasis.
On examination, partial cystectomy specimen measured 13.5 cm × 10 cm × 4 cm. Bladder wall was involved by an ulcero-infiltrative firm white growth. Segment of small intestine measured 40 cm, sent separately, showed multiple exudate covered areas with tumor deposits in the wall. Abdominal wall deposit measured 5 cm × 4 cm × 3 cm. Microscopic examination from cystectomy specimen showed invasive UC, high grade with infiltration into perivesical fat. UC in situ, extensive areas of necrosis and lymphovascular emboli were also evident. Extensive sampling was done and no heterologous elements were seen. The tumor cells expressed P63, 34 βE12, and GATA3 [Figure 1]. Sections from ileal loop showed multiple tumor deposits throughout the wall with invasion into small bowel mucosa with similar histomorphology and IHC profile. Sections from anterior abdominal wall growth revealed diffuse sheet-like proliferation of cells having rhabdoid/epithelioid morphology displaying vesicular nuclei, single prominent nucleoli and inclusion like dense eosinophilic cytoplasm. Areas of necrosis along with brisk mitosis (3–4/hpf) were noted. No urothelial component was evident on extensive sampling. These tumor cells were negative for pan-CK, P63, 34 βE12, synaptophysin, and GATA-3. However, they expressed desmin, myogenin, and MyoD1 [Figure 2]. A p53 immunostain revealed strong, intense, and diffuse nuclear expression at the primary and metastatic abdominal wall site [Figure 3]. Overall histomorphological features in conjunction with IHC, was diagnostic of invasive UC, high grade of UB with only heterologous component de-differentiation (RMS; epithelioid type) at the metastatic abdominal site. The patient was advised neoadjuvant chemotherapy; however, he refused any further medical intervention and was subsequently lost to follow-up.
|Figure 1: (a) Bladder infiltrated by tumor cells (H and E, ×100), (b) markedly pleomorphic urothelial cells with high grade nuclear atypia and frequent mitosis (arrow) (H and E, ×400), (c) Immunostain for 34 βE 12, (d) Immunostain for GATA3|
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|Figure 2: (a) Anterior abdominal wall nodule (H and E; ×40), (b) Sheets of loosely cohesive epithelioid/rhabdoid cells with eosinophilic cytoplasm. Characteristic rhabdomyoblasts seen (arrows) (H and E, ×400), (c) Immunostain for desmin, (d) Immunostain for Myo D1|
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|Figure 3: Strong nuclear expression of p53 in (a) Urothelial carcinoma of urinary bladder. (b) Abdominal wall rhabdomyosarcoma differentiation|
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| Discussion|| |
SUC is a rare entity, accounting for only 0.6% of all bladder tumors diagnosed. Radiation and cyclophosphamide therapy increases the risk of sarcomatoid differentiation. These lesions are usually characterized by a predominant carcinoma component. The common sarcomatous elements seen are condrosarcomas, leiomyosarcoma, and malignant fibrous histiocytoma. Metastases of SUC usually has a mixed histology, with epithelial predominance.
In the present case, despite extensive sampling, no heterologous element could be demonstrated in the primary bladder tumor. Possibly, an occult microscopic focus of de-differentiation amounts to this explanation which could not be recognized. A case on similar lines was recently reported by Cuadra-Urteaga et al., who were able to demonstrate a single microscopic focus of angiosarcoma in UC of the upper urinary tract that had extensively metastasized. Smith et al. also reported two cases of histomorphological disparity at the primary metastatic site. One of their cases of UC had only sarcomatous component at metastatic site while the second case had displayed an isolated carcinomatous component at the metastatic site in an otherwise sarcoma of urinary bladder.
The histogenesis of SUC has been a matter of much discussion; however, several studies have lent support to the divergence hypothesis which contends that a single cancer stem cell gives rise to the morphologically dissimilar epithelial and mesenchymal components., Interestingly, in our case, we found an oligometastasis of RMS which in itself is uncommon in adults. Attributing RMS as a second primary in this elderly age group at the anterior abdominal wall is highly unlikely. As UC with rhabdoid differentiation , and rhabdomyosarcomatous differentiation  is a known entity, it is a more proffered explanation of the abdominal wall nodule in the current case. The common monoclonal origin of tumor cells at both sites is further supported by a similar strong, intense, and diffuse p53 expression at the primary and metastatic site. This finding is strongly supported by the results of Armstrong et al., who provided evidence of a common clonal origin between the phenotypically distinct patterns of sarcomatoid carcinoma by TP53 mutational analysis. To the best of our literature search, an oligometastasis at the abdominal wall of epithelioid RMS component of SUC has never been reported.
The metastatic site RMS in the present study showed diffuse sheet-like growth of tumor cells having relatively uniform cytomorphologic features; suggestive of epithelioid RMS. Epithelioid RMS is a newly described entity with only a handful of reports published till date. Zin et al. reported five cases epithelioid RMS in pediatric age group with a median age of 8.8 years. In their retrospective study, the patients had been diagnosed as alveolar RMS variants previously and treated accordingly. Jo et al. reviewed RMS cases reported over 18 years and re-reported 16 patients with EpiRMS. The median patient age in their study was 70.5 years. All of the reported EpiRMS cases lacked PAX3/7 FOXO1 fusion transcripts; however, no specific rearrangement has been persistently associated with this neoplasm, thus making it a distinct entity. Molecular profiling was not done in the present case; however, it adds onto the existing datasheet in terms tumor presentation and tumor site. The recognition of epithelioid RMS as a distinct entity can impact patient management by guiding appropriate oncologic treatment modalities specific for RMS.
In the present case, RMS being an aggressive tumor led to rapid tumor evolution and metastasis to abdominal wall. However, IHC is imperative to distinguish epithelioid RMS from UC with rhabdoid differentiation. Epithelioid RMS cells express myogenin and myoD1 while they are negative for pan-CK. On the contrary, UC cells with rhabdoid differentiation express pan-CK while they are negative for markers of skeletal muscle differentiation. The recommended standard guidelines are but well established for carcinosarcoma, and majority of the cases show aggressive clinical course. The present case describes rarity of an occult heterologous sarcomatous component as an exclusive metastasizing component. Judicious IHC panel can differentiate UC with rhabdoid differentiation from heterologous RMS component.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initial will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.
We sincerely acknowledge the effort put up by the dedicated staff of the Histopathology Laboratory.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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Department of Laboratory Services, Rajiv Gandhi Cancer Institute and Research Centre, Rohini Sector-5, New Delhi
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]