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Case Report Urethral Adenocarcinoma Associated with Intestinal-Type Metaplasia, Case Report and Literature Review

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Case Report Urethral Adenocarcinoma Associated with Intestinal-Type Metaplasia, Case Report and Literature Review Int J Clin Exp Pathol 2013;6(8):1665-1670 www.ijcep.com /ISSN:1936-2625/IJCEP1306007 Case Report Urethral adenocarcinoma associated with intestinal-type metaplasia, case report and literature review Christopher S Hale1, Hongying Huang1, Jonathan Melamed1, Ruliang Xu1, Larry Roberts2, Rosemary Wieczorek1, Zhiheng Pei1, Peng Lee1 1Department of Pathology, New York Harbor Healthcare System, New York University School of Medicine, New York, NY, USA; 2Sound Shore Medical Center, New Rochelle, NY, USA Received June 6, 2013; Accepted July 8, 2013; Epub July 15, 2013; Published August 1, 2013 Abstract: The presence of glandular epithelium in urinary tract biopsies poses a diagnostic challenge. Intestinal metaplasia of the urethra may be seen in many congenital, iatrogenic, and reactive conditions, as well as in as- sociation with malignant conditions such as urethral adenocarcinoma. We present a case of a 61 year-old woman presenting with microscopic hematuria. Successive biopsies showed glandular epithelium with focal atypia in close association with inflammation, but no overt malignancy. Only on surgical resection was the associated high grade adenocarcinoma revealed. When intestinal-type mucosa is present within a urinary tract biopsy, associated malig- nancy may be present only focally. Thorough sampling and consideration of the differential diagnosis is imperative. Keywords: Urethral adenocarcinoma, intestinal metaplasia Introduction from this area were sent for histopathologic examination. After an unremarkable CT scan of Development of intestinal-type mucosa as a the pelvis, a repeat biopsy was performed with metaplastic response is a well-described phe- similar findings. Transurethral resection six nomenon in sites such as the esophagus. months later showed high grade urethral Rarely, metaplastic intestinal-type mucosa may adenocarcinoma. also be seen in the urinary tract. This is particu- larly true in the bladder, where glandular muco- Histopathology sa may be seen in the benign reactive condition cystitis glandularis [1]. Glandular cells may also The first biopsy Figure( 1) was received in two represent a primary or metastatic malignancy, parts. Hematoxylin and eosin stained, formalin- and merit careful inspection for atypical fea- fixed, paraffin embedded sections of showed tures. This diagnostic dilemma is even greater acute inflammatory exudate with mucin and when intestinal-type epithelium is seen in less rare clusters of benign glandular cells. The sec- common locations, such as the urethra. We ond part showed acutely inflamed benign uro- report the case of a urethral biopsy containing thelium with squamous and glandular metapla- areas of intestinal-type glandular tissue, which sia. Trichrome and smooth muscle actin stains on resection proved to be associated with high- demonstrated expected submucosal composi- grade urethral adenocarcinoma. tion of fibro connective tissue without desmo- plasia. An immunostain for PIN-4 (p63, 34βe12 Clinical presentation and AMACR) demonstrated positivity for p63 and 34βe12 in an area of squamous metapla- A 61 year-old woman was found to have micro- sia, as well as within a periurethral glandular scopic hematuria on routine medical examina- remnant. The adjacent area of glandular meta- tion. Cystoscopic work-up revealed a ragged, plasia lacked PIN-4 immunoreactivity. An area red lesion on the anterior mid-urethra. Biopsies of squamous metaplasia and an area of residu- Urethral adenocarcinoma and intestinal-type metaplasia Figure 1. A: H&E shows predominately benign glandular cells; B: a periurethral Skene’s gland and an area of squa- mous metaplasia are highlighted by p63 and 34βe12, but not AMACR (PIN-4 cocktail). Adjacent glandular metapla- sia lacks immunoreactivity. Figure 2. A: H&E shows an area of bland appearing intestinal-type metaplasia; B: Ki-67 immunostain shows focally increased proliferation. al Skene’s gland tissue both showed strong atypical glandular cells. Trichrome and smooth nuclear reactivity for p63. The metaplastic muscle actin stains demonstrated expected glandular cells lacked p63 immunoreactivity. submucosal composition without desmoplasia Nuclear Ki-67 reactivity in the areas of squa- or invasion. mous metaplasia showed 10% reactivity in a basal pattern, whereas Ki-67 positivity in the Six months after the repeat biopsy, transure- glandular areas was 5%. thral resection was performed. During the pro- cedure, bimanual examination showed a fusi- After an unremarkable CT scan of the pelvis, a form mass surrounding the entire urethra and repeat biopsy was performed. The repeat biop- bladder neck. Cystoendoscopy showed a fusi- sy (Figure 2) was processed as described form papillary-nodular tumor involving the blad- above and showed glandular intestinal-type der neck, proximal, mid and distal urethra, but epithelium with clusters of highly atypical cells not the urethral meatus. The tumor was resect- within the superficial lamina propria, as well as ed and submitted in multiple specimens for his- fragments of benign squamous epithelium. tology (Figure 3). Tissue from the bladder neck Significant chronic inflammation was present in showed intestinal metaplasia with severe atyp- most of the biopsy parts. An immunostain for ia, similar to the earlier biopsies; however, tis- Ki-67 showed 85% nuclear positivity in the sue from the anterior urethra demonstrated 1666 Int J Clin Exp Pathol 2013;6(8):1665-1670 Urethral adenocarcinoma and intestinal-type metaplasia Figure 3. Sections from the initial transurethral re- section show (A) extensive intestinal metaplasia with atypia and (B) invasive adenocarcinoma with (C) lam- ina propria involvement. high grade invasive adenocarcinoma associat- Significant atypia was present on each biopsy, ed with extensive intestinal metaplasia with but chronic inflammation and associated atypia. The tumor invaded the lamina propria, benign glandular tissue prevented an unequiv- but did not involve the muscularis propria. ocal diagnosis of adenocarcinoma. Only on Prominent proliferative cystitis was also resection was the patient’s high grade adeno- present. carcinoma definitively shown in association with the severely atypical glandular epithelium. Following systemic chemotherapy (Ifex, Taxol, This highlights the importance of adequate and Carboplatin), residual tumor remained on sampling in diagnosis of glandular urethral MRI. Examination under anesthesia showed lesions. abarely palpable mass extending from the prox- imal urethra to the meatus. Repeat transure- The origin of female primary urethral adenocar- thral resection was performed and submitted cinomais not fully understood. Prostate-specific in several specimens for histology. Histology antigen (PSA) expression inprimary urethral showed adenomatous changes with focal high adenocarcinoma supports an origin from grade dysplasia/focal carcinoma in situ, with female periurethral (Skene’s) glands [2, 3]. no invasive carcinoma. More recently, PSA non-reactive, mAbDas1- reactive cases of primary urethral adenocarci- Discussion noma have been reported in association with The differential diagnosis for glandular lesions intestinal metaplasia, leading to speculation in the female urethra is challenging and that some cases of female primary urethral includes developmental heterotopia, intestinal- adenocarcinoma may arise from malignant type metaplasia, and adenocarcinoma. In this transformation of urethritis glandularis, a con- case, the etiology of the glandular epithelium dition histologically characterized by intestinal was unclear despite two sets of biopsies. metaplasia [3, 4]. In this case, the lack of PSA 1667 Int J Clin Exp Pathol 2013;6(8):1665-1670 Urethral adenocarcinoma and intestinal-type metaplasia expression in the glandular tissue and lack of Intestinal-type metaplasia has also been atypia in the adjacent periurethral glands point reported in association with posterior urethral towards a non-periurethral gland origin (Figure polyps or “caruncles”. In addition to intestinal- 1). type epithelium, metaplasia of urethral polyps may also exhibit squamous or rarely even gas- The role of intestinal metaplasia in genitouri- tric-type differentiation [12]. Paneth cell meta- nary tract carcinogenesis is not known. One ret- plasia was an unusual finding in another case rospective study of 19 patients with intestinal [13]. Metaplastic change in urethral polyps metaplasia of the bladder did not find evidence could arise as the result of mechanical irrita- that intestinal metaplasia represents a precur- tion, or as a reaction to the inflammation that sor to bladder adenocarcinoma [5]. Intestinal gave rise to the polyp. Analogy has been made metaplasia could still be a precursor lesion to between this process, solitary rectal ulcer syn- adenocarcinoma more distally in the urinary drome, and inflammatory cloacogenic polyps tract. A case report of a woman with an exter- [7]. Stricture of the prostatic urethra in men nal urethral meatus tumor found mucinous has also been reported in association with adenocarcinoma in close association with both intestinal metaplasia with dysplasia [14]. intestinal metaplasia and urethritis cystica, Similar mechanical obstruction or stricture in suggesting a connection [3]. In this case, a con- the female urethra could also lead to metaplas- tinuum of dysplastic changes is present: benign tic response. Another study of over 300 pros- glandular mucosa, glandular mucosa with tatic urethra specimens has suggested that severe atypia, and high grade adenocarcinoma.
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