Bladder & urothelial tract

• Rare, < 1 case per 1 million of population
• 10 - 30% of bladder adenocarcinomas, 0.2 - 0.3% of all bladder cancers (J Urol 2012;188:1102, Rare Tumors 2016;8:6257)
• Age: fifth to sixth decade (younger than nonurachal adenocarcinomas; median age 52 - 56 versus 69 years) (Cancer 2006;107:721, Urol Oncol 2016;34:388)
• M:F = 2:1 (Dis Markers 2018;2018:7308168)

• Usually dome of bladder, occasionally anterior wall of bladder (intramural mass)

• Embryologic derivative undergoing neoplastic transformation (J Urol 1984;131:1)
• Risk factors include bladder exstrophy and urachal anomalies

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• Since the entire length of the median umbilical ligament may harbor urachal remnants and carcinoma may present in perivesical tissue, staging is different than bladder carcinoma
• Staging of urachal carcinoma has reduction in substages (applied to invasion of the bladder wall) and management differs according to the pathologic stage at the time of surgery (Hum Pathol 1996;27:240)
• First staging proposed by Sheldon (J Urol 1984;131:1, Urol Oncol 2016;34:388)
  • I: confined to urachal mucosa (in situ)
  • II: urachus invasion confined to urachus itself
  • III: local extension
    • Bladder (IIIA)
    • Abdominal wall (IIIB)
    • Peritoneum (IIIC)
    • Other viscera (IIID)
  • IV
    • Metastasis to regional lymph nodes (IVA)
    • Distant sites (IVB)
• Local recurrence and metastatic disease are common (J Urol 2007;178:74, Cancer 2006;107:712)
• 5 year cancer specific survival rate is ~50% (median ~45 months, significantly longer than bladder urothelial carcinoma) (Cancer 2006;107:712, Hum Pathol 2015;46:1808, J Urol 2006;175:2042, Dis Markers 2018;2018:7308168)
• In Sheldon classification, > 80% patients presented in stage III (bladder invasion) with 5 year survival rate from 25 - 61% (J Urol 1984;131:1, Urol Oncol 2016;34:388)
• Mayo and Ontario staging systems simplify the Sheldon staging using larger dataset (2006) (Cancer 2006;107:712, J Urol 2006;175:2042)
• In the Mayo system
  • Bladder mucosa and muscularis propria invasion are stage II instead of III
  • Regional lymph node involvement is stage III instead of IVA
  • Distant metastasis is stage IV instead of IVB
• In 2023, a new TNM staging system was proposed based on the 626 cases included in Surveillance, Epidemiology, and End Results (SEER) database as follows (Cancer Med 2023;12:2752)
  • Stage I
    • pT0, Ta, Tis (confined to urachal mucosa)
    • N0, M0
  • Stage II
    • pT2, pT3a (invasion of bladder muscularis propria or microscopic invasion of perivesical tissue)
    • N0, M0
  • Stage III
    • pT3b, 4a (macroscopic invasion of bladder perivesical tissue or invasion of uterus, vagina, prostate)
    • N0, M0
  • Stage IV
    • pT4b (invasion of pelvic wall, abdominal wall or peritoneum)
    • Any nodal involvement or distant metastasis regardless of pT category
• Staging systems have prognostic utility but lack validation because of the overall smaller sample size due to disease rarity (Cancer Med 2023;12:2752, Hum Pathol 2015;46:1808)

• 30 year old woman with vertebral metastasis (Arch Pathol Lab Med 2004;128:1043)
• 49 year old man with primary urachal signet ring cell carcinoma (Front Oncol 2022;12:1034245)
• 54 year old man with in situ adenocarcinoma of the urachus arising in a giant urachal cyst and associated pseudomyxoma peritonei (J Clin Pathol 2003;56:152)
• 55 year old man with enteric type tumor (Can J Urol 2009;16:4753)
• 70 year old patient with malignant transformation of urachal cyst (J Cancer Res Ther 2022;18:291)

• Umbilectomy with partial cystectomy, possibly laparoscopic (Clinics (Sao Paulo) 2008;63:731)
• Since the entire length of median umbilical ligament may harbor urachal remnants, which may develop carcinoma synchronously or metachronously, the surgery of choice includes en bloc resection of the entire length of the ligament with umbilectomy with negative margins
• Adjuvant treatment given depending on the stage includes chemoradiation

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• Firm, white-gray mass with epicenter in the anterior wall or dome of bladder with urachal tract
• Usually lacks intraluminal mass or surface mucosal changes
• Could be cystic with abundant mucin production (Am J Surg Pathol 2014;38:1033)
• Ulceration with previous biopsy site or if endophytic growth (Am J Surg Pathol 2012;36:432)
• Median size is 6 - 7 cm (Dis Markers 2018;2018:7308168)

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• Arises from intramural portion of urachus, grows into bladder wall, lacks mucosal involvement, is sharply demarcated from normal epithelium and lacks intestinal metaplasia
• Most tumors are well differentiated adenocarcinomas with histologic variations of mucinous / colloid (57%), enteric (15%), signet ring (6%), mixed morphology (8%) or nonspecific / NOS (14%) (Dis Markers 2018;2018:7308168)
• Mucinous neoplasms are predominant
• Mucinous cystic tumors form a spectrum from cystadenoma to mucinous cystic tumors of low malignant potential to microinvasive and frankly invasive cystadenocarcinomas similar to other organs (i.e., appendix, ovary) (Am J Surg Pathol 2014;38:1033)
• Residual benign urachal remnants can be intermingled with carcinoma and harbor preinvasive lesions
• Enteric subtype is morphologically identical to colorectal primary carcinomas
• Signet ring subtype is characterized by infiltrative stromal growth of signet ring cells
• < 5% of cases present with other malignant epithelial neoplastic morphology such as usual urothelial, squamous cell carcinoma and neuroendocrine (Adv Anat Pathol 2016;23:71)

Contributed by Maria Tretiakova, M.D., Ph.D.

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• CK20, CDX2, CK7, high molecular weight keratin, CD15, CEA (Am J Surg Pathol 2011;35:787, Dis Markers 2018;2018:7308168)
  • CK7 is more frequent (~50%) than in colonic primary
• High molecular weight keratin is the most useful marker to differentiate from negative colonic primary

• Local extension of colonic or other adenocarcinoma:
  • Clinical history, radiological and endoscopic investigation are important
  • Diffuse nuclear immunoreactivity for beta catenin suggests nonurachal colorectal carcinoma; diffuse positivity for 34 beta E12 supports urachal carcinoma (Am J Surg Pathol 2009;33:659, Adv Anat Pathol 2016;23:71)
• Metastatic adenocarcinoma:
  • Clinical history is important
• Nonurachal primary adenocarcinoma of bladder:
  • Usually posterior wall or trigone
  • Intraluminal mass, carcinoma in situ or extensive glandular metaplasia of adjacent urothelium
• Invasive urothelial carcinoma with glandular differentiation:
  • Usual urothelial carcinoma with urothelial carcinoma in situ is noted in the vicinity
  • Positive urothelial markers (e.g., uroplakin II, S100P, p63 and GATA3)
• Villous adenoma:
  • Noninvasive

The photomicrograph depicts urachal adenocarcinoma. Which of the following is the most important criterion for the diagnosis of urachal adenocarcinoma?

1. Beta catenin nuclear positivity on immunohistochemistry
2. Intraluminal mass in posterior wall
3. Intramural mass in dome or anterior wall
4. Presence of carcinoma in situ in mucosal lining

C. Intramural mass in dome or anterior wall. Considering the embryologic aspect, the most important criterion for urachal origin is the presence of an intramural mass in the dome or anterior bladder wall. Answers B and D are incorrect because lack of intraluminal mass and absence of carcinoma in situ favor urachal origin over primary bladder origin. Answer A is incorrect because nuclear beta catenin is often positive in colonic adenocarcinoma, which may extend or metastasize in rare cases and excludes urachal origin.

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Reference: Urachal adenocarcinoma

What is the importance of diagnosing primary urachal origin in a malignant glandular neoplasm of the bladder and perivesical area?

1. Familial predisposition
2. It arises from embryologic remnant
3. Rarity of disease representing scientific curiosity
4. Staging and management are different than bladder primary

D. Staging and management are different than that of primary adenocarcinoma of the bladder. The urachus is a fibrous cord extending from the bladder wall to the umbilicus; along the free surface of the bladder urachus, carcinoma is frequently amenable to partial cystectomy if it presents as a solitary mass. The entire tract of median umbilical ligament must be excised. Staging of urachal carcinoma differs from those that arise from the bladder surface. Most urachal carcinomas (80%) present at advanced stages but are still associated with a better survival rate than bladder urothelial carcinomas (Hum Pathol 2015;46:1808). Answer A is incorrect because no familial predisposition has been described.

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Reference: Urachal adenocarcinoma