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A Man With Changes in the Urinary Bladder: Benign Metaplasia or Adenocarcinoma?

A Man With Changes in the Urinary Bladder: Benign Metaplasia or Adenocarcinoma?

SECOND OPINION
Multidisciplinary Consultations on Challenging Cases

The University of Colorado Denver School of Medicine faculty holds weekly second opinion conferences focusing on cancer cases that represent most major cancer sites. Patients seen for second opinions are evaluated by an oncologic specialist. Their history, pathology, and radiographs are reviewed during the multidisciplinary conference, and then specific recommendations are made. These cases are usually challenging, and these conferences provide an outstanding educational opportunity for staff, fellows, and residents in training.

The second opinion conferences include actual cases from genitourinary, lung, melanoma, breast, neurosurgery, gastrointestinal, and medical oncology. On an occasional basis, ONCOLOGY will publish the more interesting case discussions and the resultant recommendations. We would appreciate your feedback; please contact us at second.opinion@uchsc.edu.

E. David Crawford, MD
Al Barqawi, MD
Guest Editors

University of Colorado Health Sciences Center
and Univeristy of Colorado Cancer Center
Denver, Colorado

The patient is a 39-year-old man who presents with pelvic lymphadenopathy. He has a history of ureteral reflux disease, recurrent nephrolithiasis, right nephrectomy, ileal loop diversion of the left ureter, and radical cystectomy for “bladder cancer,” which he underwent 3 years ago. The lymphadenopathy was discovered incidentally during recent imaging.

Case Report

History

Dr. Thomas Flaig: This patient has a complex medical and surgical history that is remarkable for several urologic problems and procedures. As a young child, he had severe ureteral reflux disease, and 30 years ago, he underwent a right nephrectomy to remove a nonfunctioning kidney that was damaged by the reflux. At the same time, he had an ileal loop diversion on the left side, presumably to prevent similar damage to the left kidney. The patient also has a history of recurrent nephrolithiasis requiring extracorporeal shock-wave lithotripsy on multiple occasions.

Three years ago, as part of a workup for hematuria, cystoscopic evaluation revealed a bladder mass. The patient reports that he was diagnosed with “bladder cancer” and had a radical cystectomy. He is now seen in our center for evaluation of nephrolithiasis and was found to have lymphadenopathy in the pelvis.

His past medical history is notable for multiple sclerosis. A review of his family history is significant for multiple sclerosis in his mother, but no history of cancer in any first-degree relatives. His social history reveals ongoing tobacco use.

Physical Exam

Dr. Flaig: On physical exam, the patient’s temperature is 96.6°F, pulse rate is 66/min, respiratory rate is 16/min, and his blood pressure is 132/72 mm Hg. He is in no acute distress. His lungs are clear to auscultation bilaterally. The cardiac exam reveals a regular rhythm without murmur. His abdomen is soft and nontender. Surgical scars are present and consistent with previous operative procedures. An ostomy site is present on the left side of the abdomen. His extremities are without any sign of infection or gross inflammation.

Laboratory Findings

Dr. Flaig: Laboratory findings include the following: sodium, 140 mMol/L; creatinine, 1.0 mg/dL; ALT, 26 U/L; total bilirubin, 0.5 mg/dL; albumin, 4.2 g/dL; white blood cell count, 10.9 × 109/L; hemoglobin, 16.3 g/dL; and platelets, 266 × 109/L.

Discussion

Pathology

Dr. Flaig: Dr. La Rosa, would you please review the patient’s pathologic findings?

FIGURE 1
Specimen #1—Histologic examination of a 3-year-old cystectomy specimen showed extensive proliferation of glands in the lamina propria (H&E, 4x objective).
FIGURE 2
Specimen #2—Cystectomy specimen showing submucosal glands lined by columnar epithelium, including goblet cells and Paneth cells (intestinal metaplasia) (H&E, 20x objective).

Dr. Francisco La Rosa: We reviewed for second opinion diagnosis the outside surgical pathology case established for this patient, consisting of a urinary bladder biopsy and a cystectomy specimen from 3 years ago. Histologic examination of the cystectomy specimen showed extensive proliferation of glands in the lamina propria (Figure 1), which were lined by columnar epithelium, including goblet cells and Paneth cells ­(Figure 2). Some sections showed pools of mucinous material with extravasation into the stroma (Figure 3).

FIGURE 3
Specimen #3—Cystectomy specimen showing pools of submucosal mucinous material with extravasation into the stroma (H&E 20x objective).

Even though the diagnosis in the outside pathology report for the biopsy specimen was of an “adenocarcinoma,” we found no evidence of significant nuclear atypia, mitotic activity, necrosis, or signet ring cells. In addition, no evidence of stromal reaction or significant chronic inflammation was present around the glands and the mucinous pools. The muscularis propria had no evidence of invasion. Also submitted for our review were three right iliac lymph nodes taken at the time of the cystectomy, which showed no evidence of malignancy.

Tumors of the urinary bladder are mostly (> 90%) derived from the urothelium (transitional cell mucosa) and are usually composed of papillary formations with different grades of malignant differentiation and potential for invasion.[1] Some of these tumors may present with areas of squamous and/or glandular differentiation. In contrast, cystitis cystica and cystitis glandularis are rare benign metaplastic changes of the urinary bladder characterized by an increased growth of the normal glandular elements within the bladder mucosa (Brunn glands). These are primarily reactive changes usually associated with chronic inflammatory processes, and should not be considered premalignant lesions. The histologic features are nests of von Brunn glands with cystic changes, which define cystitis cystica, and mucin-filled goblet cell metaplasia, which defines cystitis glandularis. In our discussion case, we observed these changes, both in the biopsy and in the cystectomy specimens.

Cystitis glandularis is found mostly in the trigone. The cystic dilatation of the glands is followed by progressive flattening of the glandular epithelium, giving origin to the morphologic changes known as cystitis cystica. Cystitis glandularis may be seen with microscopic changes in small aggregates of mucosal glands, but it may also occur as grossly identifiable poly­poid masses suggesting a neoplastic process.

The histopathologic findings of cystitis glandularis and cystica should not present a diagnostic problem. The issue arises when we need to differentiate between these benign lesions and adenocarcinoma.[2,3] Cystitis glandularis and cystica are characterized by only minimal nuclear atypia without the observation of any stromal reaction, as is seen in invasive adenocarcinoma. The glands in cystitis glandularis and cystica show a well defined outline, whereas the glands in cases of adenocarcinoma are irregular and show an infiltrative behavior. Thus, invasiveness, irregular glandular contours, desmoplastic stromal reaction, and nuclear atypia are the main features that define an adenocarcinoma. Extravasation of mucinous material into the stroma may be seen in the intestinal type of cystitis glandularis—as an isolated finding, it may be difficult to differentiate from a malignant process.[4,5]

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