Rom J Morphol Embryol 2011, 52(3 Suppl):1153–1156 R J M E ASE EPORT Romanian Journal of C R Morphology & Embryology http://www.rjme.ro/
McKittrick–Wheelock syndrome: a rare etiology of acute renal failure associated to well-differentiated adenocarcinoma (G1) arising within a villous adenoma
LILIANA ANA TUŢĂ1), MĂDĂLINA BOŞOTEANU2), MARIANA DEACU2), E. DUMITRU3)
1)Department of Nephrology 2)Department of Pathology 3)Department of Gastroenterology Faculty of Medicine, “Ovidius” University, Constanta Emergency County Hospital, Constanta
Abstract Introduction: Large villous adenomas or adenocarcinomas of the rectum can determine secretory diarrhea, associated with a depleting syndrome of prerenal acute renal failure, hyponatremia, hypokalemia, and hypoproteinemia, with favorable prognosis if early detected and properly treated. The syndrome is rare, with approximately 50 cases reported in the literature. Aim: Acute renal failure, caused by fluids and electrolytes hypersecretion, secondary to a malignant rectal villous adenoma is revealed in a 55-year-old patient, admitted with major hydro-electrolytic and acid-base disturbances to our Nephrology Department. Case Presentation: The 55-year-old male patient had a nine months history of mucous diarrhea, for which he was treated unsuccessfully by GP’s and infectionists. The symptomatology aggravated progressively and the patient was admitted through ICU with oligoanuria, severe dehydration and hydro-electrolytic and acid-base disturbances. Rectosigmoidoscopy revealed a giant villous adenoma at the rectum. Conservative therapy initially improved, and finally normalized renal function and made possible surgical resection of the tumor, with an excellent evolution afterwards. Conclusions: The McKittrick–Wheelock syndrome is a rare, life-threatening condition that requires interdisciplinary medical diagnosis and treatment, but has a good prognosis if renal function is recovered in time and makes possible curative tumoral resection. Keywords: villous adenoma, hydro-electrolytic disturbances, acute renal failure.
Introduction (BP 85/60 mmHg, with sinusal tachycardia – pulse 112 beats/min.). Biological parameters: leukocytosis Villous adenomas causing secretory diarrhea and (18 600/mm3), severe nitrate retention (serum creatinine severe hydro-electrolytic and acid-base disturbances are 9.18 mg/dL, urea 279.9 mg/dL), Na+ (108 mmols/L), known as the McKittrick–Wheelock syndrome, as it was K+ (2.39 mmols/L), Cl- (50 mmols/L), bicarbonates first described in 1954 [1, 2]. The McKittrick–Wheelock (30 mEq/L), hypoproteinemia (4.6 g/dL), hyperuricemia syndrome classically describes secretory diarrhea (31.7 mg/dL), collected fecal specimens – negative for associated with a depleting syndrome of dehydration, any infective cause. Abdominal ultrasound examination acute renal failure, hyponatremia, hypokalemia, and reveals a solid tumoral mass with a diameter of ~9 cm in hypoproteinemia. Prognosis is usually good, especially the pelvic region. Rectosigmoidoscopy shows a large after fluid and electrolyte replacement, with early villous tumor until 7–8 cm from anal region; the rest of recourse to definitive surgery. The syndrome is rare, the sigmoid was normal (Figure 1). There was no with approximately 50 cases reported in the literature evidence of metastatic disease. [3, 4]. We report a case of this uncommon syndrome After intensive therapy of fluids and electrolytes and review the literature on the possible mechanisms. replacement, we obtained recovery of the renal function + (creatinine 1.09 mg/dL, urea 40 mg/dL, Na 145 mmol/L, Patient, Methods and Results K+ 3.5 mmol/L, Cl- 108 mmol/L) after seven days from A 55-year-old male was admitted through ICU admission. After the preoperative assessment, a low accusing in the last nine months mucinous diarrhea, anterior resection of the rectum was carried out. followed in the last two weeks by nausea, vomiting, The pathological evaluation of the surgical specimen malaise and recently onset of oligoanuria. He was revealed peculiar features of the lesion. Gross examined from the onset of the symptomatology by examination of the segment of colon removed during GP’s and infectionists and discharged for several times specific surgical procedure identified an exophytic and with presumptive diagnosis of infective gastroenteritis. infiltrative mass of 12×10 cm, localized at the distal Clinically, on this last admission, he was dehydrated extremity of the specimen and at 13 cm distance from
1154 Liliana Ana Tuţă et al. the proximal surgical border. The external surface of cytoplasmic ratio due to karyomegaly and decreased the tumor had a papillary and irregular configuration, cytoplasmic volume, hyperchromatic or vesicular nuclei gray-reddish color with hemorrhagic areas, variable with prominent nucleoli and coarse chromatin; nuclei consistency. The proliferation completely obstructed the were stratified and reached luminal border (Figure 4). colic lumen (Figure 2). A supplementary argument for the malignant Microscopic analysis evidenced histopathological character of this glandular proliferation consisted in the features of villous adenoma, with its characteristic evidence of the infiltrative pattern of the malignant fingerlike projections composed of typical intestinal glands that invaded desmoplastic stroma and induced epithelium with apical secretion of mucin (Figure 3). the appearance of an inflammatory response (Figure 5). This benign neoplasm was accompanied by the The use of PAS special stain revealed the muco- presence of glandular structures lined by multilayered secretant nature of the glandular structures, with both cells with marked cyto-nuclear atypia, suggestive intra- and extraluminal accumulation of mucin (Figure 6). for diagnosis of well-differentiated adenocarcinoma Histopathological diagnosis: well-differentiated (G1). Malignant features comprised increased nucleo- adenocarcinoma (G1) arising within a villous adenoma.
Figure 2 – Macroscopic aspect of the lesion: protrusive and infiltrative character.
Figure 1 – Rectosigmoidoscopy: large villous tumor.
Figure 3 – Villous adenoma: branching papillary Figure 4 – Malignant glandular structures lined by projections with preserved nuclear polarity (HE stain, multilayered epithelial atypical cells, with karyomegaly, ×200). conspicuous nucleoli, coarse chromatin (van Gieson stain, ×400).
Figure 5 – Malignant glandular structures with Figure 6 – Mucosecretant nature of the neoplastic infiltrative pattern into a desmoplastic stroma (van structures (PAS stain, ×200). Gieson stain, ×40).
McKittrick–Wheelock syndrome: a rare etiology of acute renal failure associated to well-differentiated… 1155
Discussion endocavitary irradiation (recurrence rate of ~32% of rectal adenomas), endoscopical resection (high risk of Colonic villous adenomas occur usually in the recurrence), surgical resection of the tumor [12, 13]. rectum and rectosigmoid regions. These adenomas are Our patient underwent rectal amputation with generally sessile and may be up to 10 cm in diameter. permanent iliac stoma and the postoperatory evolution The malignant potential of adenomatous polyps was favorable until the time being, with maintenance increases with size, villous configuration, and degree of of normal levels of renal function and electrolytes dysplasia. Secretory villous adenomas are different from and no local recurrence of the carcinoma, almost four non-secretory villous adenomas on light microscopic years after tumoral resection followed by chemo- and ultra structural examination. In secretory villous therapy. adenoma, there is an exaggerated mucous production, explaining secretory diarrhea [5, 6]. Ultrastructural Conclusions study of villous adenomas shows that secretory villous adenomas are hypersecretory, with atypical goblet The McKittrick–Wheelock syndrome arises from the cells that produce a mucin of abnormal composition severe dehydration and electrolyte depletion that occurs [5, 7]. as a complication of colonic villous adenoma. These The depletion syndrome characterized by cardio- adenomas exude large quantities of electrolyte-rich vascular collapse, acute renal failure, hyponatremia and fluid. Severe orthostatic hypotension and prerenal acute a hypokalemic, hypochloremic metabolic acidosis is renal failure may occur. A key diagnostic feature is a rare complication of a rectal villous adenoma. greatly elevated blood urea nitrogen with proportionately Characteristically there is watery, mucinous diarrhea lesser elevation of serum creatinine. This syndrome is with increased bowel action. As the tumor size increases a rare, life-threatening condition that requires multi- the enteral losses overwhelms compensatory mechanisms disciplinary cooperation for diagnosis and treatment, but and the patient may seek medical attention. Digital has a good prognosis if renal function is recovered in rectal examination might miss sometimes even large time, and makes possible curative tumoral resection. tumors in many case, due to their soft, mucin-covered surface, often described as velvet-like [7, 8]. References The mechanism of fluid and electrolyte loss is [1] McKittrick LS, Wheelock FC, Carcinoma of the colon. 1954, unclear. The theoretical explanation for this is that the Dis Colon Rectum, 1997, 40(12):1494–1495; discussion 1495–1496. more distal and larger the lesion, the more likely the [2] Tjandra JJ, Cuthbertson AM, Penfold C, Sessile adenomas bowel is unable to subsequently absorb the large of the rectum: a personal series 1974–1984, Aust N Z J secretory output of the tumour. Jacob et al found that in Surg, 1990, 60(11):883–886. [3] Konishi S, Nakada I, Satani T, Kasuga T, Watanabe Y, a patient with a secretory villous adenoma that there Tabuchi T, Villous rectal adenoma as a rare cause of was increased adenylate cyclase activity compared to acute renal failure (McKittrick-Wheelock syndrome), Colo- patients with non-secretory tumors [9]. proctology, 2010, 30(4):251–253. 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After Bond JH, Church TR, Robertson DJ, Smith-Warner SA, indomethacin or somatostatine administration in Jacobs ET, Alberts DS, Greenberg ER, A pooled analysis of patients with the secretory rectal villous adenoma, the advanced colorectal neoplasia diagnoses after colonoscopic stool concentration of PGE2 markedly decreased, as did polypectomy, Gastroenterology, 2009, 136(3):832–841. the patient’s stool volume, combined with a similar [6] Hamilton SR, The adenoma-adenocarcinoma sequence in the large bowel: variations on a them, J Cell Biochem reduction in the stool sodium excretion. When the Suppl, 1992, 16G:41–46. indomethacin was stopped, the stool PGE2, sodium, and [7] Snhitka T, Friedman MHW, Kidd E, Mackenzie W, Villous volume once again increased [11]. This study suggests tumors of the rectum and colon characterized by severe that the use of prostaglandin synthetase inhibitors can be fluid and electrolyte loss, Surg Gynecol Obstet, 1961, 112:609–621. used to reduce the stool output in patients with secretory [8] Caliskan C, Makay O, Firat O, Uğuz A, Akgün E, Korkut MA, distal tumors, but caution should be taken with this McKittrick-Wheelock syndrome: is it really rare? Am J treatment when the patient has dehydration and renal Emerg Med, 2010, 28(1):105–106. failure. Still, our option is for fluid and electrolyte [9] Jacob H, Schlondorff D, St Onge G, Bernstein LH, Villous replacement, even in high levels of nitrate retention, adenoma depletion syndrome. Evidence for a cyclic nucleotide-mediated diarrhea, Dig Dis Sci, 1985, 30(7):637– better, if possible, than hemodialysis, with early recourse 641. to definitive surgery [10, 11]. Secretory diarrhea should [10] Steven K, Lange P, Bukhave K, Rask-Madsen J, not be always equated with the development of Prostaglandin E2-mediated secretory diarrhea in villous metabolic acidosis. Alkalosis is most likely to develop adenoma of rectum: effect of treatment with indomethacin, Gastroenterology, 1981, 80(6):1562–1566. when the stool electrolytes [(Na+ + K+) - Cl-] are less - [11] Popescu A, Orban-Schiopu AM, Becheanu G, Diculescu M, than plasma HCO3 . Hydro-electrolytic balance is McKittrick-Wheelock syndrome – a rare cause of acute required before radical therapy [9, 12], which may be: renal failure, Rom J Gastroenterol, 2005, 14(1):63–66.
1156 Liliana Ana Tuţă et al. [12] Kelly S, Lee P, Robertson G, Profound hypokalaemia [13] Miles LF, Wakeman CJ, Farmer KC, Giant villous adenoma secondary to a large rectosigmoid villous tumour, N Z Med J, presenting as McKittrick-Wheelock syndrome and pseudo- 2007, 120(1253):U2514. obstruction, Med J Aust, 2010, 192(4):225–227.
Corresponding author Liliana Tuţă, Associate Professor, MD, PhD, Department of Nephrology, Emergency County Hospital, Faculty of Medicine, “Ovidius” University, 145 Tomis Avenue, 900591 Constanţa, Romania; Phone +40722–300 505, Fax +40241–662 071, e-mail: [email protected]
Received: February 2nd, 2011
Accepted: October 25th, 2011