Hematuria During Pregnancy: An Unusual Presentation of Inverted Papilloma


Inverted papilloma (IP) of the urinary tract is an uncommon tumor that is usually regarded as benign. The exact cause of IP is presently unknown, although various theories have been postulated. It typically occurs during the fifth or sixth decade of life. Although IP has been reported in the pediatric age group, its occurrence in a young female during pregnancy has never been reported. The present case is a 24-year-old female who presented with gross hematuria in the 16th week of pregnancy. She had IP of the urinary bladder with extensive squamous metaplasia. Immunohistochemistry showed positivity with human papillomavirus strain 16. Transurethral resection of the bladder tumor was completed and there was no recurrence 16 months later. Squamous metaplasia has been defined as a diagnostic feature of IP, but its extensive presence during pregnancy raises questions about the influence of hormones on its development.

KEYWORDS: Inverted Papilloma; Pregnancy; Squamous metaplasia; Urinary bladder

CORRESPONDENCE: Dr. Punit Tiwari, Department of Urology, Institute of Post Graduate Medical Education and Research, SSKM Hospital, 242, AJC Bose Road, Kolkata, West Bengal, 700020, India ().

CITATION: Urotoday Int J. 2010 Jun;3(3). doi:10.3834/uij.1944-5784.2010.06.13

ABBREVIATIONS AND ACRONYMS: HPV, human papillomavirus; IP, inverted papilloma




Inverted papilloma (IP) of the urinary bladder is an uncommon urothelial tumor. Although it is generally regarded as a benign neoplasm, there are conflicting data on its association with synchronous and metachronous urothelial carcinoma [1]. Little is known about the etiology of IP; many theories are given but none are conclusive [1,2]. A recent study showed a relationship between human papillomavirus (HPV) and IP [3].

The purposes of the present case report are: (1) to describe a female who was pregnant and had IP of the urinary bladder with extensive squamous metaplasia, and (2) to highlight the role of HPV in causing IP. The present case is the only known IP of this type reported in the English literature.


A 24-year-old primigravida female presented at gestation week 16 with gross hematuria. She had recurrent urinary retention and passage of blood clots for the past 2 days. She had no history of urinary tract infection, stone disease, smoking, exposure to any drug, or any previous urological problems. She was in good health but exhibited mild pallor.


The patient was admitted to the hospital, where catheterization was done. Abdominal examination revealed a uterus that was 16 weeks in size and ballotable. The fetal heart rate was 160 beats per minute. Vaginal examination was normal. Laboratory data were within normal limits, including coagulation profile. Urine cytology showed no abnormal cells.

An ultrasound examination of the abdomen showed a mass in the posterior wall of the urinary bladder (Figure 1a) and a healthy fetus (Figure 1b). The upper urinary tracts were normal.

Cystoscopy was performed. It revealed small irregularly shaped blood clots and grossly bloody urine that was evacuated with a gentle bladder wash. There was a sessile growth that involved approximately the distal half of the trigone and extended up to the bladder neck; it was covered with slough (Figure 1c).

Management and Histological Evaluation

Transurethral resection of the bladder tumor (TURBT) was done with cauterization of the base. Histological examination showed that the polyp surface was lined with smooth benign transitional epithelium from which cords inverted and extended deep into the core of the polyp. These cords created a mosaic of epithelial tissue separated by fibrous stroma. The connective tissue was scanty, giving rise to a distinct trabecular arrangement with peripheral pallisading of the tumor cells. There was an extensive area of squamous metaplasia without atypia (Figure 2a). Individual cells were transformed into polygonal or round shapes with centrally placed round nuclei. The cells were characterized by clear vacuolated cytoplasm and distinct margins (Figure 2b). At some places, intracellular bridges were well delineated. Immunohistochemistry done with HPV 6, 11, 16, and 18 showed positivity with HPV 16 (Figure 2c); the remaining tests were negative.

The patient delivered a healthy child 5 months after surgery. She received ultrasound and cystoscopy examinations regularly for the past 16 months and has had no recurrence to date.


Many cases of IP have been reported since it was first described by Potts and Hirst in 1963 [4]. IP of the urinary tract is an uncommon tumor that is usually regarded as benign. It typically occurs in the fifth or sixth decade of life. Although IP has been reported in the pediatric age group [5], its occurrence in a young female during pregnancy has never been reported.

The exact etiology of IP is not yet fully understood. One theory is that it is caused by hyperplasia due to chronic inflammation [2]; another is that it is a neoplasm [1]. HPV 16 and HPV 18 are known to be associated with various diseases of the external genetalia and urinary system, including the urinary bladder. However, association of HPV with IP of the bladder is very rare [6]. Chan et al [3] concluded that HPV type 18 may play some role in the pathogenesis of IP. However, the present case showed negative response to HPV 18 and positive response to HPV 16 (by microwave based antigen retrieval method). HPV 16 is more prevalent in the patient's geographic region. A strong male predominance exists in this area, with a male/female ratio of 3:1 to 7:1.

Macroscopic hematuria and dysuria are the main presenting complaints, as in the present case. Although ultrasonography of the bladder may sometimes reveal a bladder mass, cystoscopy remains the diagnostic procedure of choice. Urine cytology has not been reported as useful in the diagnosis of urinary bladder IP. The shedding of cells is unlikely when an intact layer of normal mucosa covers it. However, the presence of suspicious or malignant cells in urine cytology should alert the physician to the need for closer surveillance and reevaluation of the histological finding. The accuracy of the histological diagnosis of IP is pivotal in determining its natural history. Henderson et al [7] defined 6 diagnostic criteria for IP: (1) inverted configuration, (2) covering layer of urothelium, (3) uniformity of the epithelial cells, (4) absence or rarity of mitoses, (5) formation of microcysts (crypts), and (6) presence of squamous metaplasia. However, it can still be difficult to differentiate this lesion from low-grade transitional cell carcinoma (TCC), cystitis cystica, cystitis glandularis, and von Brunn's cell nests. Although the histological distinction from lesions such as cystitis cystica and cystitis glandularis do not affect the clinical outcome, it is necessary to differentiate IP from low-grade TCC because the latter might recur and/or progress. The present patient's characteristics were similar to those found in published studies, differing only in the presence of extensive squamous metapalsia. The metaplasia may have been due to hormonal changes during pregnancy.

Transurethral resection has been performed in almost all reported cases of IP, including the present. Incomplete tumor resection contributes to a high recurrence rate. Therefore, the present authors view IP recurrence with caution, especially if it recurs in a similar location. In the present case, no recurrences have developed in 16 months of follow-up after delivery. Although squamous metaplasia is described as one of the key histological diagnostic features of IP, its extensive presence during pregnancy is unusual. Whether hormonal status during pregnancy plays any role in this extensive squamous metaplasia is a matter of conjecture. Further studies are needed to answer this question and to study the role of HPV-16 as a etiological factor of IP.


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