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Papillary urothelial neoplasm of low malignant potential with osseous metaplasia in a 19-year-old chronic smoker: A case report with review of literature


1 Department of Pathology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
2 Department of Urology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India

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Date of Submission06-Jun-2021
Date of Decision31-Dec-2021
Date of Acceptance01-Jan-2022
Date of Web Publication26-May-2022
 

   Abstract 


Urothelial tumors characteristically occur in elderly persons, more commonly in males with typical complaints of hematuria. Although few studies attempted to describe clinic-pathological features of urothelial malignancies in young patients, due to heterogeneity in the inclusion of age groups under “young patients” no reliable conclusions can be derived. Herein, we are describing an interesting case of papillary urothelial neoplasm of low malignant potential with osseous metaplasia in a 19-year-old chronic smoker young patient presented with chief complaints of abdominal pain with a review of the literature.

Keywords: Osseous metaplasia, papillary urothelial neoplasm of low malignant potential, urothelial tumor


How to cite this URL:
Gupta RK, Wasnik P, Sharma AR. Papillary urothelial neoplasm of low malignant potential with osseous metaplasia in a 19-year-old chronic smoker: A case report with review of literature. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Feb 5]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=345889





   Introduction Top


Urothelial malignancies in young adults are very rare with an incidence of only 0.1% to 0.4% in patients younger than 20 years.[1],[2] Urothelial tumors in young patients (<20 years) are more common in males and are predominantly low grade with a better outcome.[3] The majority of urothelial tumors in young patients are noninvasive including low-grade, papillary urothelial carcinomas, and papillary urothelial neoplasm of low malignant potential (PUNLMP).[2] Diagnosis of urothelial tumors in young patients may be delayed due to less suspicion and unusual clinical presentations. Herein, we report a case of PUNLMP with osseous metaplasia (OM) in a 19-year-old young chronic smoker male patient presented with abdominal pain without hematuria.


   Case Report Top


A 19-year-old chronic smoker male presented with the chief complaints of left lower abdominal pain since 2 days. No history of burning micturition, fever or chills, dysuria or stone related episodes of pain or hematuria was present. Both urine cytology and culture were unremarkable. Ultrasound showed a mass lesion measuring 13.3 × 9.6 mm in right posterior wall of urinary bladder with increased vascularity and irregular mucosa along with left vesicoureteric junction calculus (4.5 mm) and mild hydronephrosis in left kidney [Figure 1]a. The computed tomography (CT) urography showed an obstructive calculus at left vesicoureteric junction (VUJ) with upstream hydroureteronephrosis and thickened urinary bladder wall around VUJ. Near right VUJ, an enhancing polypoidal soft tissue density lesion was also noted [Figure 1]b and [Figure 1]c. Cystoscopy showed a pedunculated small papillary bladder tumor in right posterior wall. Bilateral ureteroscopic lithotripsy and trans-urethral resection of bladder tumor (TURBT) with deep muscle biopsy were performed. Post-resection, intravesicle mitomycin-C (40 mg) instillation for 90 min was done. The patient was discharged on fourth day and is symptom-free at 10-month follow-up.
Figure 1: (a) Ultrasound image showing a mass lesion (arrow) in right posterior wall of urinary bladder with increased vascularity and irregular mucosa, (b) and (c) CT urography showing an enhancing polypoidal soft tissue density lesion (arrow) near right vesicoureteric junction

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Pathological findings: The hematoxylin and eosin sections showed multiple fragmented papillaroid tissue pieces lined by transitional epithelium with the presence of fibrovascular cores [Figure 2]a. The papillary fragments showed increased thickness of urothelium with relatively maintained polarity and focal preserved umbrella cells in the surface layer. The cells were relatively monomorphic with nuclear enlargement, mild hyperchromatia, and inconspicuous nucleoli [Figure 2]b. Occasional mitotic figures were seen on basal layer. Multiple pieces of bone formation with osteoblastic rimming were also noted in the stroma [Figure 2]c and [Figure 2]d. Deep muscle biopsy did not reveal any invasive tumor. A final diagnosis of PUNLMP with OM was made.
Figure 2: Histopathology image showing (a) a papillaroid tumor fragments lined by transitional epithelium with the presence of fibrovascular cores (HE × 40), (b) the papillary fragments show increased thickness of urothelium and maintained polarity comprise of relatively monomorphic cells with nuclear enlargement, mild hyperchromatia, and inconspicuous nucleoli (HE × 100), (c) multiple pieces of stromal bone formation (HE × 100), and (d) Metaplastic bone showing osteoblastic rimming (arrow) (HE × 400)

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   Discussion Top


Bladder tumors in adolescents and young adults are very rare and have a good prognosis owing to the low-grade malignancy and the low rate of recurrence.[1] Cigarette smoking is a known major risk factor for bladder cancer, which may imply in young patients too.[2] This patient also had a history of chronic smoking. Polat et al.[1] in their series also reported history of chronic smoking in two patients. In addition, genetic factors play an important role in causing bladder tumor in young age group; however, the importance of occupational exposure is uncertain in young patient. Though painless hematuria is the major symptom, in this case, the patient presented with abdominal pain only. Stanton et al.[2] found abdominal pain as second most common presenting symptom in young adults with bladder tumors.

PUNLMP is characterized by increased urothelium thickness, maintained polarity, and minimal cellular atypia. It forms discrete exophytic papillary lesions of different sizes. Though PUNLMP poses a risk of recurrence and progression to low-grade urothelial carcinoma, it very rarely can advance to invasive carcinoma.[4],[5]

OM is a very rare phenomenon in bladder tumors, which can be occasionally seen in primary as well as metastatic invasive high-grade transitional cell carcinoma, and must be differentiated from sarcomatoid carcinoma.[6] Till date, no cases of PUNLMP with OM in young adults are described in the literature.

Several hypotheses postulated for metaplastic bone formation in urothelial carcinomas but exact mechanism and pathogenesis need to be further elucidated particularly in young patients. Pang[7] suggested that the capability of urothelium to maintain a high level of calcium, phosphate, and alkaline phosphatase activity is responsible for OM. Another theory suggested a possible role of bone morphogenetic protein 2 (BMP2) in the transformation of stromal mesenchymal cells into osteoblasts, particularly in previously operated cases having scar and fibrous tissue.[8] Other factors of osteogenesis encompassing specific transcription factors like OCT3/4, SOX-2, c-Myc, and Klf4 generating pluripotent stem cells are also described for playing role in OM in bladder tumors.[9] Assuming all hypotheses proposed, OM requires the presence of osteogenic precursor cells, inducers like growth factors/transcription factors, and a suitable milieu containing minerals. Razafimahefa et al.[10] in their paper summarized 19 cases of bladder carcinoma with OM (12 cases in primary tumors and 7 cases in metastatic locations) with a single pediatric case of noninvasive high-grade urothelial carcinoma (niHGC) in a 3-year-old child. Our case of PUNLMP and niHGC in 3-year-old child[6] with OM explain a possible genetic predisposition, which may also be implicated despite the absence of particular triggering factors. The definite prognostic significance of OM in bladder cancers is not described; however, its occurrence in predominantly high-grade primary and metastatic urothelial carcinomas indicates toward aggressive behavior of such tumors.[10]

Urinary bladder hamartomas are extremely rare and may be associated with osteoid-like metaplasia and should be considered as a differential for urothelial tumors with OM.

Cystoscopy is the standard procedure for the evaluation of gross hematuria and the detection of intravesical growth. Sometimes, ultrasound is very helpful for initial investigation, particularly in patients presenting with other symptoms like abdominal pain and no hematuria. Resection of tumor is the treatment of choice, regardless of age. As most cases of urothelial tumors in young adults are low grade, an aggressive follow-up with cystoscopy is not advised; a simple ultrasound-based follow-up is sufficient.[1] Polat et al.[1] also suggested that intracavitary chemotherapy after TURBT is not required in young adults due to the rarity of recurrence.

To conclude, urothelial tumors in young adults are usually low grade with excellent prognosis; however, due to heterogeneity in the age group under “young adults” in different literature, a clear treatment and follow-up guideline is still not formulated. Similar to the general population, chronic smoking is an important risk factor for urothelial tumors in young adults. OM is a very rare phenomenon described in few high-grade primary and urothelial carcinoma likely denoting aggressive behavior; however, interestingly, we have found OM in a case of PUNLMP in a young adult, which warrants a close follow-up.

Acknowledgment

We would like to thank Dr Nikhil Balpande, Senior resident, Dept of Radiodiagnosis, AIIMS, Raipur, for his support in radiological examination.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Polat H, Utangac MM, Gulpinar MT, Cift A, Erdogdu IH, Turkcu G. Urothelial neoplasm of the bladder in childhood and adolescence: A rare disease. Int Braz J Urol 2016;42:242-6.  Back to cited text no. 1
    
2.
Stanton ML, Xiao L, Czerniak BA, Guo CC. Urothelial tumors of the urinary bladder in young patients: A clinicopathologic study of 59 cases. Arch Pathol Lab Med 2013;137:1337-41.  Back to cited text no. 2
    
3.
Fine SW, Humphrey PA, Dehner LP, Amin MB, Epstein JI. Urothelial neoplasms in patients 20 years or younger: A clinicopathological analysis using the world health organization 2004 bladder consensus classification. J Urol 2005;174:1976-80.  Back to cited text no. 3
    
4.
Jaworski D, Szylberg Ł, Gzil A, Stawinski P, Kasperska A, Marszałek A. Diagnostic difficulties in cases of papillary urothelial neoplasm of low malignant potential, urothelial proliferation of uncertain malignant potential, urothelial dysplasia and urothelial papilloma: A review of current literature. Ann Diagn Pathol 2019;40:182-8.  Back to cited text no. 4
    
5.
Maxwell JP, Wang C, Wiebe N, Yilmaz A, Trpkov K. Long-term outcome of primary papillary urothelial neoplasm of low malignant potential (PUNLMP) including PUNLMP with inverted growth. Diagn Pathol 2015;10:3.  Back to cited text no. 5
    
6.
Skarda J, Michalek J, Tichy T, Smakal O, Kral M. Kodet R. High-grade non-invasive transitional cell carcinoma with osseous metaplasia of the 3-year-old boy urinary bladder. J Clin Exp Pathol 2015;5:236.  Back to cited text no. 6
    
7.
Pang LS. Bony and cartilaginous tumours of the urinary bladder. J Pathol Bacteriol 1958;76:357-77.  Back to cited text no. 7
    
8.
Boudabbous S, Arditi D, Paulin E, Koessler T, Rougemont AL, Montet X. Ossifying metaplasia of urothelial metastases: Original case with review of the literature. BMC Med Imaging 2015;15:30.  Back to cited text no. 8
    
9.
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861-72.  Back to cited text no. 9
    
10.
Razafimahefa J, Gosset C, Mongiat-Artus P, Andriamampionona TF, Verine J. Stromal osseous metaplasia in urothelial carcinoma of the bladder: A rare case report and literature review. Diagn Pathol 2019;14:75.  Back to cited text no. 10
    

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Correspondence Address:
Rakesh K Gupta,
Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, GE Road, Tatibandh, Raipur - 492 099, Chhattisgarh
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_611_21



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