Sarcomatoid carcinoma in a bladder diverticulum: A rare case

542 LETTER TO THE EDITOR SYMPTOMATIC HYPOCALCEMIA OWING TO ORAL RISEDRONATE THERAPY Sir, A 21-year-old man was admitted to our hospital because of intermittent diarrhea from his childhood and weight loss. Physical examination was normal (1.55 m height and 43 kg weight). Laboratory studies were as follows; serum total calcium (Ca2+): 8.8 mg/ dl, phosphorus: 5 mg/dl, magnesium: 1.6 mg/ dl, albumin: 3.7 mg/dl, total protein: 5.7 mg/ dl. Serum sodium, potassium, alkaline phosphatase levels, and renal, hepatic, and thyroid function tests were normal. Serum parathyroid hormone (PTH) level was 139 pg/ ml. Antigliadin immunoglobulin A (IgA) antibody was positive. Severe villous atrophy in the proximal intestine was found in histopathologic examination. Bone mineral densitometry (DEXA) revealed significant osteoporosis (L1– L 4, Z, and T scores were 3.24 and -3.23, respectively). According to these data, he was diagnosed with celiac disease and implemented on a gluten free diet, oral risedronate (35 mg/once a week), oral calcium (elemental calcium 1800 mg/day) and oral magnesium (1830 mg/day). Three days after the starting dose of risedronate, he experienced a full picture of hypocalcemia with physical and laboratory findings (albumin-corrected serum Ca2+ of 5.9 mg/dl) including long QT interval in the ECG. Other results were; phosphorus 3.1 mg/dl, magnesium 1.7 mg/dl, and albumin 3.4 mg/ dl. Then, he was treated with intravenous calcium gluconate. He recovered well with this therapy, and discontinued risedronate and continued with oral calcium, magnesium and vitamin-D3 besides gluten free diet. Use of the Naranjo adverse drug reaction probability scale indicated a possible (score: 4) relationship between symptomatic hypocalcemia and risedronate therapy in this patient.[1] 543 LETTER TO THE EDITOR caused hypomagnesemia as well. Since PTH secretion is stimulated by magnesium dependent adenly cyclase, it is possible that hypomagnesemia exacerbated hypocalcemia by interrupting the normal feedback loop. Therefore, correction of the hypomagnesemia seems essential in such patients. In conclusion, symptomatic hypocalcemia is a rare but possible complication of oral risedronate therapy. Patients with celiac disease should be checked for their calcium and vitamin-D status, and carefully followedup during risedronate treatment. REFERENCES Bisphosphonates are recommended especially in old patients with celiac disease, and, given the serious consequences of spontaneous fractures can also be considered at younger ages.[2] These drugs, when given intravenous, have occasionally been reported to cause symptomatic hypocalcemia. [3] However, as in the present case, it is quite uncommon with oral administration[4,5] because of compensatory mechanisms such as increase in PTH secretion, which prevents hypocalcemia by enhancing renal absorption of calcium, vitamin-D production, and stimulating osteoclastic bone resorption. Depending on the potency of the bisphosphonate, the effect of PTH on bone resorption by osteoclasts is blocked to some extent during bisphosphonate treatment. Gastrointestinal calcium absorption occurs mainly in the proximal ileum and decreases towards the distal par ts. In our case, the diarrhea might have impaired calcium absorption in response to hypocalcemia. Presumably, gastrointestinal calcium loss Indian J Med Sci, Vol. 59, No. 10, October 2005 1. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al., A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239–45. 2. Scott EM, Gaywood I, Scott BB. Guidelines for osteoporosis in coeliac disease and inflammatory bowel disease. British Society of Gastroenterology. Gut 2000;46(Suppl 1):i1–8. 3. Singh D, Khaira NS, Sekhon JS. Symptomatic hypocalcaemia after treatment with zoledronic acid in a patient with multiple myeloma. Ann Oncol 2004; 15:1848. 4. Johnson MJ, Fallon MT. Symptomatic hypocalcemia with oral clodronate. J Pain Symptom Manage 1998;15:140–2. 5. Mayordoma JI, Rivera F. Severe hypocalcaemia after treatment with oral clodronate and aminoglycoside. Ann Oncol 1993;4:432–3. SARCOMATOID CARCINOMA IN A BLADDER DIVERTICULUM — A RARE CASE Sir, Sarcomatoid carcinoma are those, which exhibit a prominent spindle cell component. They are aggressive tumours with a poor prognosis and should be differentiated from true carcinosarcoma.[1] So far, only two cases of sarcomatoid carcinoma in a bladder diverticulum have been reported. This 56-year-old patient presented with total painless hematuria of 1-month duration. Physical examination was negative. CT examination showed a large bladder diverticulum containing an irregular contrast enhancing mass (Figure 1). On cystoscopy, a large diverticulum with a nodulopapillary tumour with keratin material on surface was seen. Biopsy of the tumour reported a high­ grade spindle cell neoplasm. The patient underwent bilateral pelvic lmphadenectomy, radical cystoprostatectomy with MAINZ II T. DOGRU, A. SONMEZ, I. TASCI, H. GENC Gulhane Medical School, Department of Internal Medicine, Etlik, Ankara, Turkey Correspondence Teoman Dogru. Gulhane Medical School, Department of Internal Medicine, Etlik, 06018, Turkey E-mail: teomandogru@yahoo.com Indian J Med Sci, Vol. 59, No. 10, October 2005 Figure 1: Contrast enhanced CT scan showing the neck of the diverticulum communicating with bladder LETTER TO THE EDITOR ureterosigmoidostomy. The lymph nodes and resected margins were negative. Histopathology repor t proved to be sarcomatoid carcinoma. The tumor was composed of transitional cell carcinoma (TCC), sarcomatous spindle cells and the area of transition between TCC and spindle cells [Figure 2(inset)]. Immunohistochemical examination showed that the spindle cells and the area of transition were strongly positive for vimentin and weakly positive for cytokeratin (Figure 2). The histopathological and immunohistochemical transition between the TCC and the spindle cells implies that the sarcomatous elements originated from the TCC during tumour progression. The patient expired 6 months after surgery with extensive pelvic lymph node recurrence and lung metastasis. The occurrence of a tumor inside a diverticulum is relatively rare. The TCC is the commonest tumor seen in a diverticulum. About 19 cases of intradiverticular sarcomas and carcinosarcomas have been reported in Figure 2: Microphotograph (100x) showing strongly positive vimentin areas. (Inset) Microphotograph (400 x) shows pleiomorphic sarcomatoid cells with hyper chromatic nuclei (H&E staining) 544 the literature. Of these only two cases are of sarcomatoid carcinoma. [2] Patients with intradiverticular tumours usually present with hematuria, voiding difficulty, palpable mass. Neoplasms originating in a bladder diver ticulum are character ized by ear ly transmural invasion and tendency for higher histopathological grades.[3] This makes early diagnosis and treatment imperative in these tumours. Filling defects caused by intradiverticular tumors may not always be visualized in intravenous urogram (IVU) and cystography. Cross-sectional imaging studies like US, CT, and magnetic resonance imaging (MRI) are being used with greater accuracy in the diagnosis and staging of intradiver ticular tumours. MRI imaging in oblique planes can facilitate the diagnosis by demonstrating the neck of the diverticulum. Also, T2 weighted images allow differentiation between tumor in a diver ticulum and a necrotic extravesical mass. [4] Cystoscopic findings of keratin materials and fast growing tumours also warrant special attention. As in our case, these signify a more sinister pathology than the usual TCC. Cystoscopic biopsy may not be diagnostic always as superficial biopsy may be inconclusive. The neoplasm’s or iginating in a bladder diver ticulum are character ized by ear ly transmural invasion and high incidence of local recurrence. [5] The previously reported cases treated with partial cystectomy had rapid intra abdominal recurrences and dismal prognosis. Our case demonstrates the accuracy of CT in detecting intradiverticular tumours. Obtaining a deep biopsy by cystoscopy is essential for diagnosis. The intradiver ticular sarcoma and sarcomatoid carcinoma portend a poor prognosis even Indian J Med Sci, Vol. 59, No. 10, October 2005 545 LETTER TO THE EDITOR with aggressive surgical resection. REFERENCES 1. Young RH, Wick MR, Mills SE. Sarcomatoid carcinoma of the urinar y bladder. A clinicopathologic analysis of 12 cases and review of the literature. Am J Clin Pathol. 1988; 90: 653–61 2. Kim MY, Jeon YS, Suh CH, Park WH. Sarcomatoid carcinoma arising from the diverticulum of the urinary bladder dome: a difficult diagnosis with imaging. Am. J. Roentgenol. 1999; 172: 1454-5 3. Yagci C, Atasoy C, Fitoz S, Akyar S. Cross sectional imaging findings in intradiverticular bladder tumor­ a case report. Tani Girisim Radyol.2003; 9:452-5 4. Durfee SM, Schwartz LH, Panicek DM, Russo P. MR imaging of carcinoma within bladder diverticulum. Clinical Imaging 1997; 21:290-2 5. Cheng CW, Ng MT, Cheung HY, Sun WH, Chan LW, Wong WS, Lai FM. Carcinosarcoma of the bladder diverticulum and a review of the literature. Int J Urol. 2004; 11:1136-8. T. A. KISHORE, S. BHAT, A. S. ALBERT, J. AUGUSTINE Department of Urology and Pathology, Medical College, Kottayam, Kerala, India Correspondence TA Kishore Department of Urology, Medical College, Kottayam – 686008, Kertala, India, E-mail: kishoreta@yahoo.com Indian Journal of Medical Sciences is pleased to announce the launch of its website. The URL of the website is http://www.indianjmedsci.org. The features of the site are: • • • • • • • • • Free full text availability of articles in HTML as well as PDF Link to abstracts and full text from the cited references Link to PubMed abstracts of published articles by authors Link to related articles in PubMed Link from text of articles to various databases and search engines Facility to submit comments on articles Email notifications on new issue release Statistics of articles download and visits Structure based on OpenURL, DC Metadata and other international standards Indian J Med Sci, Vol. 59, No. 10, October 2005