See related article, Dzeletovic I et al, on page e47 in CGH. See related article, Dzeletovic I et al, on page e47 in CGH. Question: A 52-year-old woman presented to the emergency department complaining of a perianal bleeding tumor confining her to bed rest. On examination, the patient was found to have a large anal exophytic condylomatous lesion involving both buttocks with cephalad extension to the vulva and labia (Figures A and B). Bleeding areas and numerous fistulous sinus tracts were evident. Her laboratory values were otherwise remarkable for hemoglobin of 6.8 g/dL. Her past medical history disclosed cervix circumcision for intraepithelial dysplasia. The patient developed nausea, vomiting, disorientation, and hallucinations. A marked severe acute hypercalcemia developed within 24 hours (serum calcium level from 10 to 17.2 mg/dL), which was refractory to saline diuresis, zolendronic acid, and calcitonin. A hypercalcemia workup was performed disclosing raised parathyroid hormone–related protein (PTHrP) and low active vitamin D3 [1-25(OH)2VD3] plasma levels. The metastatic workup, including computed tomography of the head, chest, and abdomen, as well as pelvic magnetic resonance imaging (MRI), was unremarkable apart from a potential local invasion of the coccyx by the tumor and enlarged bilateral inguinal lymph nodes (Figure C). What was the cause of the refractory hypercalcemia and why did calcium levels continue to rise despite aggressive medical management? Look onpage 2025for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. The patient was urgently taken to the operating room for a wide perineal dissection and an en-block tumor and partial coccygeal resection. After surgery, her calcium levels normalized. Histology revealed an invasive squamous cell carcinoma with positive margins arising in a giant anal condyloma acuminatum. Grade III anal intraepithelial neoplasia was also present. Consequently, she underwent radical surgery and chemoradiotherapy. To our knowledge this is the third reported case1Teo M. Dhadda A. Gunn J. Paraneoplastic hypercalcaemia in squamous cell carcinoma of the anus: first reported case.Clin Oncol (R Coll Radiol). 2008; 20: 718Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar, 2Hernandez J.M. Shibata D. Paraneoplastic hypercalcemia caused by an invasive squamous cell carcinoma arising from a giant anal condyloma acuminatum.Int J Colorectal Dis. 2009; 24: 359-360Crossref PubMed Scopus (3) Google Scholar of hypercalcemia of malignancy caused by squamous cell carcinoma arising in a giant anal condyloma acuminatum. Moreover, it is the first case with refractory hypercalcemia requiring urgent tumor excision. Giant condyloma acuminatum of the anogenital tract has a 30% rate of malignant degeneration. Identification rate of human papilloma virus (HPV) DNA in invasive anal cancer ranges from 50–95%. Almost 90% are HPV subtype 16, 7% HPV 18, 6% HPV 33, 1% HPV 31, and 2% untyped. A few studies have shown an obvious progression of anal intraepithelial neoplasia to invasive carcinoma in HPV-positive patients.3Frisch M. Glimelius B. Van den Brule A.J.C. et al.Sexually transmitted infection as a cause of anal cancer.N Engl J Med. 1997; 337: 1350-1358Crossref PubMed Scopus (575) Google Scholar We observed positive endonuclear hybridization sign for HPV DNA-subtypes 31/33 in many superficial squamous cells and koilocytes of the specimen (Figure D). The most important mechanisms involved in hypercalcemia of malignancy are (1) secretion of PTHrP (It is the leading mechanism in most cases). The gene encoding PTHrP exists in the short arm of chromosome 12 and is expressed at low levels in many normal tissues including keratinocytes. Poorly differentiated keratinocytes produce the largest amount of PTHrP. (2) Direct osteolytic metastases with release of local cytokines (in our case—coccygeal invasion) and (3) secretion of 1,25-dihydroxyvitamin D (1,25[OH]2D3; calcitriol). There are no published guidelines for selecting among supplementary modalities in the management of refractory hypercalcemia. The exact mechanism should be seriously taken into account for tailoring a treatment regimen for patients who have had a suboptimal response to initial therapy with bisphosphonates. Human Papillomavirus–Related Rectal Squamous Cell Carcinoma in a Patient With Ulcerative Colitis Diagnosed on Narrow-Band ImagingClinical Gastroenterology and HepatologyVol. 8Issue 5PreviewA 57-year-old woman presented with an 8-year history of chronic ulcerative colitis (CUC). She had received treatment with prednisone, and was maintained in clinical remission with 6-mercaptopurine. She subsequently developed steroid refractory symptoms and hence was given infliximab. Surveillance colonoscopy revealed a subtle erythematous flat lesion in the distal rectum, not contiguous with the dentate line (FigureA). Examination with narrow-band imaging (NBI) revealed a depressed lesion with an irregular ulcerated border, loss of the normal mucosal pit-pattern, and microvasculature (FigureB). Full-Text PDF
Read full abstract