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Year : 2015  |  Volume : 11  |  Issue : 4  |  Page : 730-734

Malpingian carcinoma of the urinary bladder: A case series

1 Department of Urology, "Tzaneion" General Hospital of Piraeus, Piraeus, Greece
2 Department of Urology, "Sismanoglion" General Hospital of Maroussi, Maroussi, Greece

Date of Web Publication15-Feb-2016

Correspondence Address:
Konstantinos Stamatiou
2 Salepoula str., 18536 Piraeus
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.147710

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 > Abstract 

Context: Malpingian carcinoma (MC) of the bladder is a rare entity. Although distant metastases are very rare it is, usually, diagnosed in the advanced stage, and most patients die.
Aims: The aim was to reveal the characteristics of this tumor and discuss reasons explaining its particular biological behavior.
Settings and Design: The pathologic and clinical characteristics, as well as treatment and outcome of six consecutive cases, were retrospectively studied.
Subjects and Methods: Medical records of patients with bladder tumors who were treated in our hospital from 2004 onward were reviewed in order to identify those with MC of the bladder.
Results: We identified found seven cases. Almost all had locally advanced disease. Three developed visceral metastases and died within few months from the time of diagnosis.
Conclusions: Monitoring protocols required for the early control of local recurrence.

Keywords: Bladder tumors, malpingian carcinoma of the bladder, squamous element

How to cite this article:
Stamatiou K, Christopoulos G, Pavlis A, Papatsoris A. Malpingian carcinoma of the urinary bladder: A case series. J Can Res Ther 2015;11:730-4

How to cite this URL:
Stamatiou K, Christopoulos G, Pavlis A, Papatsoris A. Malpingian carcinoma of the urinary bladder: A case series. J Can Res Ther [serial online] 2015 [cited 2020 Feb 26];11:730-4. Available from: http://www.cancerjournal.net/text.asp?2015/11/4/730/147710

 > Introduction Top

Malpingian carcinoma (MC) of the bladder generally represents 2-7% of all urothelial cancers with considerable geographic variability in prevalence worldwide. [1] In the western world, MC represents <5% of all bladder tumors. There are no specific diagnostic tests, and it is, usually, diagnosed in the advanced stage. Therefore, the prognosis is poor, and most patients die. The only proved predisposing factor is chronic irritation of the bladder by urinary infection, calculi, and long-term indwelling catheterization. Here, we are reviewing the pathologic and clinical characteristics of seven consecutive cases of this rare tumor.

 > Subjects and methods Top

Medical records of seven patients with bladder tumors who were diagnosed with MC of the bladder and were treated in our hospital from 2004 onwards were reviewed.

Patient demographics and prior history

Five patients were males and the remaining two female. Their median age was 72.2 years (range: 62-82 years) and most of them were older than 70 years. Only one patient presented with de novo bladder cancer while none of the remaining patients had a previous history of bladder cancer. In most of these, there was no clear evidence of a bladder tumor in the initial assessment. The diagnosis of bladder MC was established by the pathologic examination of the resected bladder tissue in all six patients.

Detailed clinical features

  1. Case 1: A 62-year-old man with no prior history of bladder cancer presented with chronic urinary retention. Upon ultrasound investigation, he was found to have an enlarged urinary bladder with a considerable amount of residual urine (>1000 ml). His prostate gland was 58 cm 3 . He also had at least three urinary bladder diverticulae of 3 cm diameter or greater (the larger of them had a diameter of 5 cm). A mild dilatation of both left and right renal pelvis was noted as well. His serum creatinine level was 6 mg/dl, and his blood urea nitrogen was 97 mg/dl. He reported difficulty in urination in the last 6 months. A catheter was placed until the normalization of blood urea nitrogen and serum creatinine levels and the patient underwent the regular diagnostic workout. Intravenous pyelography and cystoscopy confirmed the findings of the ultrasound investigation. Urine cytology revealed abundant infectious cells, however, it was negative for malignancy. Digital rectal examination was normal and serum prostate-specific antigen (PSA) value was 2.5 ng/ml. The patient underwent transurethral resection of the prostate and 7 days later bladder the diverticulectomy. Difficulty in the detachment of the larger diverticula from the surrounding tissues during the procedure revealed a soft tissue mass arising from the diverticula wall and expanding to the adjacent fat and peritoneum. Histological examination diagnosed MC of the bladder. Computed tomography (CT) scans of the abdomen and chest and complete gastroenterologic investigation excluded other locations
  2. Case 2: A 74-year-old male smoker with a history of recurrent nonmuscle-invasive grade 2 urothelial carcinoma and few transurethral resection of the bladder tumors (TUR-BTs) was admitted to our department with a bladder tumor found accidentally by abdominal ultrasound. He was asymptomatic although he had a positive urine culture. Of note, his regular follow-up examinations (cystoscopy, urine cytology, and abdominal ultrasound) 6 months prior his admission were normal. The patient underwent clinical and radiological evaluation: Cystoscopy showed the tumor to appear as a solid mass located in the posterior bladder wall while the CT scan of the abdomen was suspicious for locally advanced disease (invasion of the vesical fat). CT scans of the chest and brain as well as a bone scan were all negative for metastatic disease. Histologic examination of the TUR-BT specimens confirmed the diagnosis of locally advanced pure MC of the bladder without urothelial element
  3. Case 3: A 72-year-old patient suffering of chronic obstructive uropathy (benign prostate hypertrophy related renal insufficiency) and arterial hypertension was admitted to our hospital with anouria. His serum creatinine level was 8.5 mg/dl, and his blood urea nitrogen was 387 mg/dl. He reported a long-term catheter use-for at least 5 years-because of prostatic hypertrophy and recurrent urinary retention. Physical examination revealed a palpable mass (probably corresponding to block nodes) in the left groin [Figure 1] and an enlarged prostate gland. Abdominal ultrasound revealed excessive hydronephrosis and cortical thinning of kidneys, apparent thickening of the bladder wall, and a 120 cc volume prostate gland. CT of the abdomen showed a 6 cm solid mass in the left groin, a small solid mass in the liver, left para-aortic and internal iliac lymph nodes, and ipsilateral osteolytic lesions on the base of the puboischial ramus and the pubic body. The bladder wall was thickened, and the middle lobe of the prostate protruded in the lumen of the bladder. CT of the chest found no abnormalities. The patient's renal function was improved after five dialysis sessions and bilateral placement of percutaneous nephrostomy tubes. He underwent transdermal biopsy (fine-needle biopsy) of the mass. Histological examination diagnosed MC of unknown origin [Figure 2]. Patient subsequently underwent additional tests. Urine cytology diagnosed uroepithelial atypia while cystoscopy revealed an ulcerated area on the left lateral wall above the ipsilateral vesicoureteral junction. The patient underwent TUR-BT
  4. Cases 4 and 5: A 71 and 69-year-old women came to the emergency department of our hospital with gross hematuria. The past medical history of the older patient included episodes of cystitis associated with vesical stones while that of the younger patient included cervical carcinoma for which she had treated with radical hysterectomy. Endoscopic evaluation revealed a solitary fungating mass in the bladder in both cases. That of the first female patient was located on the bladder neck (measuring 3 cm × 2 cm in size) while that of the second was smaller, and it was found in the bladder dome. Cystoscopic biopsies were taken
  5. Cases 6 and 7: An 82 and 77-year-old men with no prior history of bladder cancer presented with a chronic hematuria. Upon ultrasound examination of the abdomen, a mass protruding from the right bladder wall of the older patient was shown while no specific findings were revealed in the younger patient. Cystoscopy confirmed the diagnosis of bladder cancer in both cases. Both patients underwent TUR-BT.
Figure 1: Computed tomography image of a 6 cm solid mass in the left groin

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Figure 2: Squamous cell carcinoma of the urinary bladder (H and E, ×100)

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 > Results Top

All specimens of MC of the bladder were obtained from TUR-BTs. The sections were fixed in 10% buffered formalin, processed in the standard fashion, embedded in paraffin, cut at 4 mm intervals, and stained with hematoxylin and eosin stain (H and E). Immunohistochemical staining was performed by the standard immunoperoxidase technique. The antibodies used included cytokeratin (CK 5, 6, 7) uroplakine III, PSA, p63, CK19, CK20, and cyclooxygenase 2 (COX-2). Cases were scored for the percentage of mixed component, necrosis, and heterologous elements.

Histologic features

  1. Case 1: The biopsy specimen consisted partly of normal diverticula wall and partly of invasive keratinizing squamous cell carcinoma involving the diverticula wall and the full thickness of the adjacent bladder wall extending into the perivesical soft tissue [Figure 2] and [Figure 3]. Surgical margins were not disease free. Immunohistochemistry study demonstrated positive stain for CK 5, 6 and COX-2 and negative for PSA, CK19 and CK20, and p63. Some of the tumor cells were immunoreactive with p63 and uroplakine III. COX-2 was expressed homogeneously and intensely in the cytoplasm of neoplastic cells [Figure 4]
  2. The biopsy specimen had an overall volume of 5 cc. Histological examination showed a well to moderate differentiated MC of the bladder. Squamous differentiation was characterized by irregular and infiltrative nests or sheets of polygonal cells with distinct cellular borders, eosinophilic cytoplasm and varying degrees of keratinization. The adjacent bladder epithelium showed dysplasia and squamous cell carcinoma in situ along with extensive squamous metaplasia. Immunohistochemical study showed that the tumor cells were positive for CK 5/6 and COX-2. Squamous metaplastic epithelium also expressed COX-2. Surgical margins were not disease free as the tumor has invaded the muscolaris propria
  3. Case 3: Histopathology examination of percutaneous biopsy specimens revealed moderate differentiated MC. In immunohistochemistry, the tumor cells were positively stained for CK5-6, partly positive for uroplakine III and negative for CK7 and PSA. Histological examination of the bladder biopsy also diagnosed stage II SCC with same immunohistochemistral characteristics
  4. Cases 4 and 5: Histological examination of the biopsy specimens showed a well-to-moderate differentiated pure MC in both cases. Squamous differentiation was characterized by irregular and infiltrative nests or sheets of polygonal cells with distinct cellular borders, eosinophilic cytoplasm, and varying degrees of keratinization. The tumors elicited areas of necrosis while the nonneoplastic tissue showed extensive squamous metaplasia (which was excessive in the first case). The immunohistochemical study showed that the tumor cells were positive for CK 5/6 and COX-2 and negative for CK19 and CK20. Some of the tumor cells were immunoreactive with p63. COX-2 was expressed homogeneously and intensely in the cytoplasm of neoplastic cells. Squamous metaplastic epithelium also expressed COX-2. In the younger patient, the tumor was confined to the urothelium while in the older one muscular invasion occurred. In this particular patient, CT scan of the abdomen showed invasion to the adjacent adipose and lymph involvement node tissue however there was no evidence of distant metastasis
  5. Cases 6 and 7: Histological examination of the TUR-BT specimens of the older patient showed a moderately differentiated MC, while that of the younger one diagnosed a poorly differentiated mixed urothelial and MC. In both cases, bladder tumors have invaded the lamina propria and the bladder muscle.
Figure 3: Well-differentiated squamous cell carcinoma of the urinary bladder (H and E, ×100)

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Figure 4: Immunohistochemical detection of cyclooxygenase 2 in squamous cell carcinoma in the urinary bladder (×200)

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Patient treatment and outcomes

  1. Case 1: Despite extended surgical excision, tumor recurrence, bacterial infection, and abscess were developed locally in due course. The patient did not responded to the antimicrobial treatment and underwent two more surgical interventions. He also developed distant metastases and died of septic shock, 26 days after the 2 nd intervention
  2. Case 2: The patient was unfit for radical surgical treatment and was advised to receive radiotherapy and adjuvant chemotherapy with cisplatin plus gemcitabine. He was found with evidence of metastatic disease at the last follow-up (18 months after diagnosis); however, he refused treatment and died 8 months after the time of diagnosis
  3. Case 3: During hospitalization, the patient had recurrent urinary tract infection that was treated with appropriate antimicrobial therapy. The patient developed multiple visceral metastases and died 4 months after the time of diagnosis
  4. Cases 4 and 5: The older patient underwent radical cystectomy. Twenty-seven months after initial diagnosis, she is alive with distant metastases to the lung. The younger patient remained under active surveillance. She was presented with local recurrence 8 months later for which she underwent TUR-BT
  5. Cases 6 and 7: The patients underwent staging, and they were found with a T3N + M0 and a T2N0M0 disease, respectively. The first patient was unfit for radical surgical treatment and was advised to receive radiotherapy and adjuvant chemotherapy with cisplatin plus gemcitabine. The second underwent radical cystectomy. Eleven months after initial diagnosis he is alive and disease free.

 > Discussion Top

Malpingian carcinoma is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of cells showing particular cytological or tissue architectural characteristics of squamous cell differentiation, such as the presence of keratin, tonofilament bundles, or desmosomes. Epidemiological studies indicate that the development of squamous cell carcinoma of the urinary bladder is closely associated with chronic inflammation of the urinary tract. In fact, MC's occur in association with schistosomiasis in 83% of the cases, [2] while urothelial carcinomas of the bladder with squamous differentiation have been associated with human papilloma virus infection. [3] Moreover, symptoms associated with MC include bladder and lower abdominal pain, urinary frequency, and nocturia which are common with that of cystitis. [4] Actually, the exact underlying mechanism is currently unknown. COX-2 is markedly expressed in all squamous cell carcinoma suggesting that chronic inflammation stimulates the production of COX-2 protein and that an increased COX-2 level in turn induces the development of squamous cell carcinoma of the bladder affecting many biological features of this tissue including apoptosis, cell adhesion, angiogenesis, and invasiveness. [2] Regarding cell adhesion, it seems that it determines its biological behavior.

Although <4% of MC cases are at risk of metastasis and hence life-threatening, [5] MC of the bladder usually has poor prognosis as most patients die within a short period from the time of diagnosis. [6] Radical cystectomy with urinary diversion appear to be the treatment of choice, but 5-year survival rates are still low ranging from 27% to 33%. [4] Why this tumor exhibits a highly aggressive behavior when located in the bladder is not known. However, the natural history of this malignancy may be linked to its histological characteristic (squamous element) and its pathogenesis. The squamous element may be present in the bladder either as a result of metaplastic transformation of the normal mucosa or through differentiation of the conventional, transitional cell carcinoma. Both represent an adaptive change which occurs in response to long-term irritation of the bladder mucosa. The pathogenesis of MC of the bladder is not clearly understood, however, it is associated with the epithelial metaplasia. The last has been extensively investigated in the cervix: Many studies demonstrated that the region of the epithelium which has undergone metaplastic changes is particularly susceptible because the immature metaplastic epithelial cells are susceptible to carcinogens and that most, if not all, cervical carcinomas develops there. [7] Respectively, in the bladder, the fully differentiated normal urothelium subjected to metaplasia is gradually converted into another type epithelium composed by stratified squamous cells, which is susceptible to mutations. In addition, keratinization, and extend of squamous metaplasia seem to play an important role in the pathogenesis of MC's. In fact, nonkeratinizing squamous metaplasia-also known as vaginal metaplasia as it is mostly found in females is limited (it normally occurs in the trigone of the bladder) and it is well-defined. It does not have clinical significance, and it is considered an anatomic variation, caused by a hormonal influx. [8] In contrast, keratinizing squamous metaplasia is associated with squamous cell carcinoma. It is considered a precancerous condition especially when more than 50% of the bladder surface is affected. [9] The exact pathophysiologic mechanism of the transformation from keratinizing squamous metaplasia to squamous cell carcinoma is not clearly understood however it is mediated by the epithelial growth factor (EGFR) a tyrosine kinase that transduces signals controlling cell proliferation. Actually, an increased EGFR receptor activity has been reported in squamous carcinomas associated to previous squamous metaplasia of the bladder. [10] Enhanced activity of EGFR is also found in the bladder of patients with muscle-invasive MC derived from keratinizing squamous metaplasia. Of note, most of these cancers are invading the muscularis propria of the urinary bladder at the time of diagnosis. [6],[11] Interestingly, conventional urothelial carcinomas containing squamous cell component displays highly aggressive behavior: More than 90% of these carcinomas are poorly differentiated (histological grade: G3) and most patients (76%) carrying these tumors are diagnosed at an advanced stage. [12],[13] Interestingly, the occurrence of disease recurrence and mortality rates of patients with transitional carcinomas with squamous differentiation is two-fold and four-fold higher than in patients without squamous differentiation, respectively. [10],[14] Whether the unfavorable prognostic value can be attributed to squamous differentiation and if it is dependent on intrinsic biologic properties of the tumor it is not known. It could be, however, assumed that the strong adhesion between cells that characterizes MCs may be associated with the aggressive nature of both primary MCs and transitional carcinomas containing foci of squamous metaplasia. In fact, structures involved in cell-to-cell adhesion and cell adhesion molecules play a significant role in cancer progression. Moreover, cell to cell interactions of cancer cells with endothelium determine the metastatic spread. In addition, direct tumor cell interactions with platelets, leukocytes, and soluble components significantly contribute to cancer cell adhesion, extravasation, and the establishment of metastatic lesions. [15] It remains obscure, how during metastases, reduced adhesion (despite the presence of retentive cytokines) permits the cancer cells to migrate from the primary site while increased adhesion capacity permits the cancer cells to settle on the secondary environment. Evidence suggests that cells cannot effectively migrate unless they can establish a number of new adhesions; however, too much adhesion may impede translocation of the cell body. In the confirmation to the above, expression of the adhesion molecule E-cadherin was not correlated with tumor progression, invasion, and metastasis in the tumor cells of MC human bladder cancer. [16] Whether and if cell adhesions serve as key sites for signal transduction and establishment of cell polarity remains also unknown. In conclusion, while monitoring protocols required for the early control of local recurrence, future studies should target the relationship between cell adhesion motility and translocation since which may be important for effective chemotaxis.

 > References Top

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Prudnick C, Morley C, Shapiro R, Zaslau S. Squamous cell carcinoma of the bladder mimicking interstitial cystitis and voiding dysfunction. Case Rep Urol 2013;2013:924918.  Back to cited text no. 4
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Wiener DP, Koss LG, Sablay B, Freed SZ. The prevalence and significance of Brunn's nests, cystitis cystica and squamous metaplasia in normal bladders. J Urol 1979;122:317-21.  Back to cited text no. 9
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Lagwinski N, Thomas A, Stephenson AJ, Campbell S, Hoschar AP, El-Gabry E, et al. Squamous cell carcinoma of the bladder: A clinicopathologic analysis of 45 cases. Am J Surg Pathol 2007;31:1777-87.  Back to cited text no. 12
Beltran H, Robinson BD, Tagawa ST. Primary squamous cell carcinoma of the urinary bladder presenting as peritoneal carcinomatosis. Adv Urol 2010:179250.  Back to cited text no. 13
Antunes AA, Nesrallah LJ, Dall'Oglio MF, Maluf CE, Camara C, Leite KR, et al. The role of squamous differentiation in patients with transitional cell carcinoma of the bladder treated with radical cystectomy. Int Braz J Urol 2007;33:339-45.  Back to cited text no. 14
Bendas G, Borsig L. Cancer cell adhesion and metastasis: Selectins, integrins, and the inhibitory potential of heparins. Int J Cell Biol 2012;2012:676731.  Back to cited text no. 15
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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