The majority of bladder lesions originate from the urothelium. Squamous cell lesions are rare and can be either benign or malignant (1). Malignant squamous lesions of the bladder include squamous cell carcinoma, squamous differentiation in urothelial carcinoma, and in situ squamous cell carcinoma (5). Benign squamous lesions include keratinized squamous metaplasia, squamous cell papilloma, verrucous squamous hyperplasia, and condyloma acuminatum.
Squamous cell papilloma localized in the bladder is extremely rare. A review of the literature reveals only three case reports published to date (5,6,7). In a study by Guo et al. (2006), 29 cases of non-invasive squamous lesions of the bladder were examined, five of which were identified as squamous cell papillomas (3). A case of a 74-year-old patient presenting with hematuria and LUTS in 2013 is presented (5). In a case report published in 2022, a case of squamous papilloma accompanied by a bladder stone was treated with TURB (7). The case reported in 2020 involved a 76-year-old woman (6). Sengupta et al. (2021) also reported a case of squamous cell papilloma localized in the urethra (4).
In clinical practice, these lesions can present with atypical symptoms such as hematuria, lower urinary tract symptoms, or suprapubic pain, but they may also be incidentally discovered. Due to its rarity, the etiology of squamous cell papilloma remains unclear. Risk factors include smoking, exposure to aromatic amines, and a history of bladder stones, as observed in our case (4). In the study conducted by Cheng et al. in 2000, no relationship was found between squamous papilloma and HPV infection (8). However, the relationship between oral squamous papilloma and HPV has been demonstrated in some studies (9).
The differential diagnosis should exclude other benign and malignant lesions of the bladder, primarily urothelial carcinoma. On cystoscopy, squamous cell papilloma typically appears as a calcified mass, which is often indistinguishable from urothelial carcinoma. Diagnosis is established through accurate pathological evaluation of tissue obtained via excisional biopsy or transurethral resection. Histologically, squamous cells are characterized by parallel alignment to the surface, abundant eosinophilic cytoplasm, and a spindle-shaped morphology, whereas urothelial cells typically exhibit moderate clear or basophilic cytoplasm and a perpendicular alignment to the surface. Squamous cell papilloma is described as a papillary, exophytic, non-invasive lesion with extensive keratinization on the surface. Immunohistochemically, p63 positivity and focal p16 positivity are significant for diagnosing squamous papilloma.
Squamous papilloma should be differentially diagnosed with keratinizing squamous metaplasia, which is considered an important risk factor for invasive carcinoma. Keratinizing squamous metaplasia, clinically known as leukoplakia, is a pathologic response to chronic inflammatory stimulation such as from infection, indwelling catheters, stones, and parasite eggs. Marked hyperkeratosis, parakeratosis, and elongation of the rete pegs were present in verrucous squamous hyperplasia. The condyloma would be larger than the papilloma, would have a broader base, and would appear pink-to-red as a result of less keratinization. HPV infection should be ruled out by the absence of morphological koilocytic features or through molecular methods (8). In cases of nuclear atypia, mitotic activity, or irregular cell clusters within the stroma suggestive of invasion, malignant tumors must be considered.
Due to its rarity and limited data in the literature, the clinical significance of squamous cell papilloma remains unclear. It is considered a benign lesion, and recurrence is believed to be rare following surgical excision (3). In the study conducted by Guo et al., 5 cases of squamous papilloma were identified and followed up for 21 months, with recurrence observed in only one case (3). In the case reported by Takei et al., recurrence was observed in the third month, but no recurrence was noted in the following 2.5 years (6). In the case reported by Miliaras et al., no recurrence was observed after 6 months of follow-up, while the follow-up duration in the case reported by Mohamed et al. was not specified (5,7). In the case of urethral squamous papilloma, no recurrence was observed after 9 months of follow-up (4). The paucity of reported cases and the short follow-up periods makes it challenging to establish follow-up recommendations.
In conclusion, squamous cell papilloma of the bladder is a rare benign lesion with characteristic microscopic and immunohistochemical features that mimic malignant bladder tumors endoscopically. Its etiology and clinical significance remain uncertain. This case emphasizes the importance of accurate pathological evaluation for urologists and underscores the need to avoid overly aggressive treatments for patients.
DISCUSSION
The majority of bladder lesions originate from the urothelium. Squamous cell lesions are rare and can be either benign or malignant (1). Malignant squamous lesions of the bladder include squamous cell carcinoma, squamous differentiation in urothelial carcinoma, and in situ squamous cell carcinoma (5). Benign squamous lesions include keratinized squamous metaplasia, squamous cell papilloma, verrucous squamous hyperplasia, and condyloma acuminatum.
Squamous cell papilloma localized in the bladder is extremely rare. A review of the literature reveals only three case reports published to date (5,6,7). In a study by Guo et al. (2006), 29 cases of non-invasive squamous lesions of the bladder were examined, five of which were identified as squamous cell papillomas (3). A case of a 74-year-old patient presenting with hematuria and LUTS in 2013 is presented (5). In a case report published in 2022, a case of squamous papilloma accompanied by a bladder stone was treated with TURB (7). The case reported in 2020 involved a 76-year-old woman (6). Sengupta et al. (2021) also reported a case of squamous cell papilloma localized in the urethra (4).
In clinical practice, these lesions can present with atypical symptoms such as hematuria, lower urinary tract symptoms, or suprapubic pain, but they may also be incidentally discovered. Due to its rarity, the etiology of squamous cell papilloma remains unclear. Risk factors include smoking, exposure to aromatic amines, and a history of bladder stones, as observed in our case (4). In the study conducted by Cheng et al. in 2000, no relationship was found between squamous papilloma and HPV infection (8). However, the relationship between oral squamous papilloma and HPV has been demonstrated in some studies (9).
The differential diagnosis should exclude other benign and malignant lesions of the bladder, primarily urothelial carcinoma. On cystoscopy, squamous cell papilloma typically appears as a calcified mass, which is often indistinguishable from urothelial carcinoma. Diagnosis is established through accurate pathological evaluation of tissue obtained via excisional biopsy or transurethral resection. Histologically, squamous cells are characterized by parallel alignment to the surface, abundant eosinophilic cytoplasm, and a spindle-shaped morphology, whereas urothelial cells typically exhibit moderate clear or basophilic cytoplasm and a perpendicular alignment to the surface. Squamous cell papilloma is described as a papillary, exophytic, non-invasive lesion with extensive keratinization on the surface. Immunohistochemically, p63 positivity and focal p16 positivity are significant for diagnosing squamous papilloma.
Squamous papilloma should be differentially diagnosed with keratinizing squamous metaplasia, which is considered an important risk factor for invasive carcinoma. Keratinizing squamous metaplasia, clinically known as leukoplakia, is a pathologic response to chronic inflammatory stimulation such as from infection, indwelling catheters, stones, and parasite eggs. Marked hyperkeratosis, parakeratosis, and elongation of the rete pegs were present in verrucous squamous hyperplasia. The condyloma would be larger than the papilloma, would have a broader base, and would appear pink-to-red as a result of less keratinization. HPV infection should be ruled out by the absence of morphological koilocytic features or through molecular methods (8). In cases of nuclear atypia, mitotic activity, or irregular cell clusters within the stroma suggestive of invasion, malignant tumors must be considered.
Due to its rarity and limited data in the literature, the clinical significance of squamous cell papilloma remains unclear. It is considered a benign lesion, and recurrence is believed to be rare following surgical excision (3). In the study conducted by Guo et al., 5 cases of squamous papilloma were identified and followed up for 21 months, with recurrence observed in only one case (3). In the case reported by Takei et al., recurrence was observed in the third month, but no recurrence was noted in the following 2.5 years (6). In the case reported by Miliaras et al., no recurrence was observed after 6 months of follow-up, while the follow-up duration in the case reported by Mohamed et al. was not specified (5,7). In the case of urethral squamous papilloma, no recurrence was observed after 9 months of follow-up (4). The paucity of reported cases and the short follow-up periods makes it challenging to establish follow-up recommendations.
In conclusion, squamous cell papilloma of the bladder is a rare benign lesion with characteristic microscopic and immunohistochemical features that mimic malignant bladder tumors endoscopically. Its etiology and clinical significance remain uncertain. This case emphasizes the importance of accurate pathological evaluation for urologists and underscores the need to avoid overly aggressive treatments for patients.