Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2022  |  Volume : 18  |  Issue : 6  |  Page : 1827-1831

Squamous cell carcinoma arising from keratinizing desquamative squamous metaplasia of renal pelvis and double paraneoplastic syndrome: Association of two rare entities

Department of Pathology, Lady Hardinge Medical College, New Delhi, India

Date of Submission11-Dec-2021
Date of Decision11-Jan-2022
Date of Acceptance11-Jan-2022
Date of Web Publication14-Sep-2022

Correspondence Address:
Md Ali Osama
Department of Pathology, Lady Hardinge Medical College, New Delhi 110001
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_2229_21

Rights and Permissions
 > Abstract 

Keratinizing desquamative squamous metaplasia (KDSM) of the upper urinary tract is a rare entity. The present case is of a 45-year-old female patient with an 8-month history of abdominal lump, recurrent right lumbar pain, intermittent fever, and oliguria. Computed tomography kidney, ureter, and bladder revealed a grossly enlarged right kidney along with heterogeneously enhancing soft tissue density mass and internal septations. A differential diagnosis of renal cell carcinoma, urothelial carcinoma, tuberculosis, and pyonephrosis of the kidney was considered as per the clinical and radiological presentation. Intraoperatively, thick fluid was seen in the kidney and its pedicle was seen adhered to duodenum. Partial nephrectomy was done and on microscopic examination squamous cell carcinoma (SCC) was seen arising in the setting of KDSM. Postoperatively, the patient showed an exponential rise of total leukocyte count (100/153 × 103/μl) and serum calcium levels (10.1/17.2/20.4 mg/dl); eventually started deteriorating and later succumbed to illness. We report this rare association of SCC of the renal pelvis arising in KDSM along with the double paraneoplastic syndrome.

Keywords: KEY WORDS: Keratinizing desquamative squamous metaplasia, paraneoplastic syndrome, pelvis, squamous cell carcinoma

How to cite this article:
Agarwal K, Osama MA, Kavita G, Majumdar AD. Squamous cell carcinoma arising from keratinizing desquamative squamous metaplasia of renal pelvis and double paraneoplastic syndrome: Association of two rare entities. J Can Res Ther 2022;18:1827-31

How to cite this URL:
Agarwal K, Osama MA, Kavita G, Majumdar AD. Squamous cell carcinoma arising from keratinizing desquamative squamous metaplasia of renal pelvis and double paraneoplastic syndrome: Association of two rare entities. J Can Res Ther [serial online] 2022 [cited 2022 Dec 9];18:1827-31. Available from: https://www.cancerjournal.net/text.asp?2022/18/6/0/356098

 > Introduction Top

Keratinizing desquamative squamous metaplasia (KDSM) is a condition in which the urothelium of the urinary tract is replaced with keratinized squamous epithelial cells. Metaplasia of the lower urinary tract is not uncommon, however, KDSM of the upper urinary tract and renal pelvis is an extremely rare phenomenon.[1],[2],[3] This metaplastic process may be associated with chronic inflammation, irritation, smoking, or associated chronic infections. Owing to the rarity of publications describing this entity, we present this unique case of development of squamous cell carcinoma (SCC) in a metaplastic keratinized squamous epithelium of renal pelvis. This case is even more unique on account of its association with its hematological presentation of a leukemoid reaction with concomitant hypercalcemia.

 > Case Report Top

A 45-year-old female patient with complaints of the right abdominal lump since 8 months, presented to the hospital. This was associated with recurrent lumbar pain, intermittent fever, and gradual reduction in urine output. With the current complaints and medical history, the patient was admitted in the surgery department. On investigations, the patient was found to be anemic (hemoglobin 7.3 g/dl, red blood cell count 3.4 million/mm3) platelet count was on the higher side of normal-360 × 103 μL. The initial total leukocyte count was 47 × 103/μl which increased to 68 × 103/μl on the 3rdday. Toxic granules were not seen on peripheral smear examination. The patient developed fever on the 2ndday of admission. Physical examination revealed a right abdominal lump measuring 15 cm × 8 cm. The mass was large, lobulated arising from the right lumbar region and extending till the umbilical region. No foul-smelling cervical discharge, bleeding per vaginum or any cervical mass was noted. Papanicolaou cervical screen test done 6 months back was negative for any intraepithelial lesion or malignancy. Chest X-ray did not show any abnormality. Ultrasonography revealed intra-abdominal fluid collection for which repeated US-guided pigtail catheter drainage was done. The aspirated fluid showed occasional pus cells; however, no atypical cells were seen. Adenosine deaminase and protein levels were also within normal range. Culture and sensitivity of the aspirated fluid showed no organism. The patient did not show any signs of improvement on intravenous antibiotics, hence, anti-tubercular therapy was empirically instituted. However, the patient failed to improve clinically. As a result, computed tomography of kidney, ureter, and bladder was done which revealed a grossly enlarged right kidney of about 21.5 cm × 10.2 cm × 5 cm and a heterogeneous enhancing soft tissue density mass with internal septations, measuring 6.6 cm × 3.7 cm × 6.9 cm [Figure 1]a. The mass was seen completely filling the right renal pelvis, pelviureteric junction, and obstructing the pelvicalyceal system. There was secondary gross hydronephrosis with thinning of the cortical renal parenchyma. The mass lesion was seen closely abutting, indenting, and compressing the adjoining part of inferior vena cava with partial intraluminal filling defect at the drainage of ipsilateral renal vein (suggestive of renal vein thrombosis). No renal stones were identified. The other kidney was unremarkable. Clinically and radiologically, a diagnosis of renal cell carcinoma with hydronephrosis was made. Further, the right kidney was found to be nonfunctional according to the Diethylenetriamine pentaacetic Acid scan. In light of the patient's clinical deterioration, nonfunctioning kidney and radiological reports; right partial nephrectomy was done. The ureter was not excised. Intraoperatively, 400–500 ml thick fluid was present in the right kidney. The renal pedicle was seen adhered to duodenum along with dense adhesions which were identified between the transverse colon loops. Grossly, a right partial nephrectomy specimen was received as multiple irregular cystic tissue pieces. Microscopically, multiple sections taken from the cystic fragments showed atrophied renal parenchyma with features of chronic pyelonephritis on the outer surface of the cyst wall. The cyst was lined by keratinizing squamous epithelium with desquamation [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f. No urothelial lining was identified on extensive sectioning. A possibility of intrarenal teratoma was considered, however, multiple sectioning of the renal pelvis did not reveal any adnexal structure or derivative of the mesoderm or endoderm, thus ruling out a teratoma. Squamous epithelium showed loss of polarity, was dysplastic at places, and showed irregular infiltrative down growths and nests of epithelium which were indicative of SCC [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e, [Figure 2]f. The nests of atypical cells were devoid of any inflammatory cells. On immunohistochemistry, the atypical cell nests were positive for CK5/6 [Figure 3]a and [Figure 3]b, p63 [Figure 3]c, and negative for CK7 [Figure 3]d, CK20 [Figure 3]e, and GATA-3 [Figure 3]f (thus ruling out urothelial carcinoma). Hence, a final diagnosis of SCC arising in a desquamative keratinizing squamous metaplasia of the renal pelvis with chronic pyelonephritis was rendered. Postoperatively, the patient did not show much signs of improvement and her overall performance status began to deteriorate with progressive weakness and anemia. Subsequent total leukocyte counts (100/153 × 103/μl) kept increasing, differential counts persistently showed neutrophilic predominance (95%/93%/88%). The neutrophil alkaline phosphatase score was 368. Peripheral smear showed only a mild left shift with no atypical cells seen. Serum calcium levels (10.1/17.2/20.4 mg/dl) also started rising exponentially in tandem. No derangement in coagulation profile was noted. A diagnosis of double paraneoplastic syndrome was made further. The patient on the 6th postoperative day developed bilateral pleural effusion and gradually started desaturating. Pleural fluid examination showed few reactive mesothelial cells; however, no atypical cells were noted. In view of worsening renal function and suspicion of sepsis, the patient was empirically started on iv antibiotics. Blood cultures revealed Methicillin-resistant Staphylococcus aureus which was sensitive to teicoplanin. Hypercalcemia was managed by aggressive hydration and bisphosphonate therapy. On the 13th postoperative day, the patient died due to metabolic acidosis, acute respiratory distress syndrome, and septic shock.
Figure 1: (a) Contrast-enhanced computed tomography kidney, ureter, and bladder showing a grossly enlarged right kidney with a heterogeneous enhancing soft tissue density mass and internal septations (white arrows); (b) squamous metaplasia of renal pelvis covered by a thick layer of keratin (H and E, ×100); (c) renal pelvis showing metaplastic keratinizing squamous epithelium with underlying atrophic tubules (H and E, ×100); (e) renal pelvis with underlying smooth muscle layer (black arrow) and compressed atrophic renal parenchyma (H and E, ×40); (f) surrounding renal parenchyma showing chronic pyelonephritis (H and E, ×200)

Click here to view
Figure 2: (a and b) Keratinizing squamous epithelium disorganization with irregular infiltrative down growths and nests of epithelium indicative of squamous cell carcinoma (black arrows) (H and E, ×100); (c) nests of tumor cells along with keratin pearls infiltrating into the surrounding normal renal parenchyma (H and E, ×40); (d and e) solid nests of tumor cells infiltrating into the surrounding normal renal parenchyma (H and E, ×100, ×200); (f) numerous keratin pearl formation (white arrow) in areas of squamous cell carcinoma (H and E, ×100)

Click here to view
Figure 3: (a) Metaplastic squamous epithelium, dysplastic epithelium and underlying tumor positive for CK5/6 (×100); (b) Tumor cells and keratin pearls positive for CK5/6 (×100); (c) p63 positivity seen in metaplastic squamous epithelium of renal pelvis and squamous cell carcinoma (×100); (d) CK7 negative in the metaplastic renal pelvis lining and the underlying tumor cells (Internal positive control- Distal renal tubules showing positivity for CK7) (×100); (e) CK20 negative staining in metaplastic renal pelvis lining and tumor cells (×100); (f) immunohistochemistry staining: GATA-3 negative (×100)

Click here to view

 > Discussion Top

Metaplasia of urothelium of the upper urinary tract is a relatively infrequent phenomenon and may either present as squamous or glandular differentiation. This protective adaptation occurs in response to a chronic injury, converting the transitional epithelial lining to a more robust keratinized squamous lining, thereby mitigating damage to the underlying stroma. Earlier, this entity was referred to as renal leukoplakia or cholesteatoma. Hertle and Andraulakakis described this histological entity as KDSM.[1] Siderits et al. reported a case of KDSM with a history of chronic renal disease and acute pyohydronephrosis.[2] Koratala et al. documented a similar metaplastic change of renal pelvis in a known chronic smoker.[3] Similarly, in the present case, the patient had a long-standing history of hydronephrosis and decreased urinary output. There is still no final consensus as to whether KDSM is a precancerous condition or a benign protective response. There are case reports of the occurrence of SCC in squamous metaplasia of renal pelvis. Brits et al. described a female with flank pain and sepsis and a hydronephrotic nonfunctioning kidney which subsequently on biopsy revealed it to be a moderately differentiated SCC.[4] SCC arising from KDSM of upper urinary tract is extremely rare. On extensive search, only one such case report has been found in published literature. Al-Marhoon et al. reported a case of a 45-year-old male smoker with an enlarged left kidney with cystic changes which on biopsy showed SCC arising from KDSM of renal pelvis [Table 1].[5] The present case will be the second case in the literature.
Table 1: Comparison of our case with other cases in literature

Click here to view

The paraneoplastic syndrome represents an interplay of complex mechanisms involving cytokines and hormones. It has a broad spectrum of presentation from clinical conditions such as fever to multifaceted clinical syndromes. Hematologic manifestations of the paraneoplastic syndrome range from derangement in coagulation profile to abnormality of blood cells and leukocytosis, as seen in this case. Hypercalcemia is more common in tumors presenting with squamous histology vis-a-vis other histopathological subtypes.[6] Musri et al., in their case of renal pelvic SCC showed a sudden rise of calcium levels postoperatively.[7] The combination of multiple paraneoplastic syndromes is a rare clinical occurrence. Our case showed an exponential rise in serum calcium levels and total leukocyte count postoperatively. Coşkun et al. reported a case of renal pelvis SCC with multiple hematological paraneoplastic syndromes including hypercalcemia, leukocytosis, and thrombocytosis which carried a worse prognosis and the patient died after few cycles of chemotherapy.[8] Although there are case reports of SCC occurring in squamous metaplasia of the upper urinary tract, to the best of knowledge, the occurrence of keratinizing SCC from KDSM along with paraneoplastic syndrome has not been documented yet. There has been some research in the field of SCC differentiation of the upper urothelial tract tumors and possible immunotherapy however no study describes the therapy to be given for the present case. Arriola et al., in their study, demonstrated immunopositivity of programmed death ligand-1 in all 14 cases (100%) with squamous differentiation of upper urothelial tract malignancies and thus provides a potential immunotherapy target in those patients where cisplatin-based chemotherapy regimens have been known to be unsuccessful in improving clinical outcome.[9]

 > Conclusion Top

We have reported this case to emphasize that a diagnosis of malignancy should be considered in a patient having a history of pyelonephritis. There is a paucity of published data in the literature about the association of renal pelvic SCC with multiple paraneoplastic syndromes. More studies are required to determine the best course of treatment for these patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

Hertle L, Androulakakis P. Keratinizing desquamative squamous metaplasia of the upper urinary tract: Leukoplakia-cholesteatoma. J Urol 1982;127:631-5.  Back to cited text no. 1
Siderits RH, Fingerman J, Hazra A, Rimmer C, Colaco M, Mikhail N, et al. Renal pelviceal keratinizing squamous metaplasia with sparing of pyramidal zones. Case Rep Urol 2012;2012:242780.  Back to cited text no. 2
Koratala A, Qadri I, Bird V, Ruchi R. Renal keratinising desquamative squamous metaplasia: All that hurts is not stone. BMJ Case Rep 2017;2017:bcr2017220682.  Back to cited text no. 3
Brits N, Bulane S, Wadee R. Primary squamous cell carcinoma of the kidney: A case report and review of the literature. Afr J Urol 2020;26:79.  Back to cited text no. 4
Al-Marhoon MS, Saparamadu PA, Venkiteswaran KP, Shareef O, Mathewkunju J. Squamous cell carcinoma arising in keratinizing desquamative squamous metaplasia (KDSM) of the renal pelvis. UroToday Int J 2013;6:49.  Back to cited text no. 5
Walls J, Bundred NJ. Squamous cell carcinoma of the renal pelvis associated with urinary diversion and humoral hypercalcaemic malignancy syndrome. J R Coll Surg Edinb 1992;37:207-8.  Back to cited text no. 6
Musri FY, Mutlu H, Eryilmaz MK, Salim DK, Tazegul G, Coşkun HŞ. Hypercalcemia associated with squamous cell carcinoma of renal pelvis: A case and review of the literature. J Cancer Res Ther 2019;15:S170-2.  Back to cited text no. 7
Coşkun HŞ, Kargı A, Özdoğan M, Bozcuk H, Savaş B. Leukocytosis, thrombocytosis and hypercalcemia as a triple paraneoplastic syndrome in a patient with squamous cell carcinoma of the renal pelvis. Turk J Haematol 2010;27:51-2.  Back to cited text no. 8
Arriola AG, Farahani SJ, Bhargava HK, Guzzo TJ, Brooks JS, Lal P. PD-L1 expression reveals significant association with squamous differentiation in upper tract urothelial carcinoma. Am J Clin Pathol 2019;151:561-73.  Back to cited text no. 9


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Case Report>Discussion>Conclusion>Article Figures>Article Tables
  In this article

 Article Access Statistics
    PDF Downloaded32    
    Comments [Add]    

Recommend this journal