Introduction

Adenomatous polyposis syndromes occupy the second place among colorectal cancer syndromes after Lynch syndrome. The last one is a syndrome associated with inherited mutation that impair DNA mismatch repair and high risk of colon cancer in young people (40—45 years), as well as other cancers [1, 2]. Polyposis syndromes are manifested by multiple benign polyps in the colon with subsequent development of colorectal cancer if surgical treatment is not applied. There are 2 main adenomatous syndromes: familial adenomatous polyposis (FAP) and MutYH-associated polyposis [3]. FAP is usually caused by various mutations of the APS gene (Adenomatous Polyposis Coli) [4]. FAP may be accompanied by other cancers.

Turcot syndrome (TS) is a hereditary syndrome characterized by combination of primary brain tumors with colorectal cancer (CRC) [5]. Various definitions of this syndrome were proposed. In 1959, Canadian surgeon Jacques Turcot was one of the first who described 2 cases of FAP combined with brain tumor in relatives. Patients were brother and sister. In the first case, polyposis and sigmoid adenocarcinoma were combined with medulloblastoma, in the second one — with glioblastoma and pituitary adenoma [6, 7]. There was no hereditary history in this case and the parents of these patients were second cousins. Therefore, autosomal recessive type of inheritance was supposed. Three years later, McKusick determined combination of primary brain tumors with FAP as Turcot syndrome [8].

Molecular genetic analysis of these siblings was performed in 1995. S. Hamilton et al. [8] found mutation of DNA mismatch repair gene (MMR) typical for Lynch syndrome. Currently, it is well known that combination of colorectal cancer and brain tumors may be secondary to various genotypes [9].

Over time, there have been repeated attempts to reclassify Turcot syndrome. To date, Turcot syndrome 1 (TS1) and Turcot syndrome 2 (TS2) are distinguished. These types are determined by combination of CRC with primary brain tumor in patients with MMR or APC gene mutations, respectively [5]. It is also known that glioblastomas are more common in patients with TS1, medulloblastomas – in those with TS2 [8—10].

It is difficult to assess incidence and prevalence of this syndrome considering its rarity and the fact that its definition has changed over the years. It is believed that this is a hereditary disease with autosomal recessive or autosomal dominant type of inheritance. However, the syndrome can also occur de novo [4]. To date, 150 TS patients have been reported in the literature [8, 11]. Obviously, this is a heterogeneous group of patients with various clinical and oncological manifestations and various genetic changes [12]. There is an experience of treatment of patients with Turcot syndrome in a family with FAP at the Ryzhikh Coloproctology Center [13]. We report own clinical observation considering rarity of these cases in the world.

Clinical observation

A 28-year-old patient D. from the Suzdal (Vladimirskaya region) first noted periodic discharge of blood and mucus with stool in 2015. At the same time there were complaints of severe headaches, dizziness, weakness, shaky gait, impaired coordination, dysarthria.

It is important to note that the patient’s hereditary history is burdened. Her father died at 48 years old from FAP followed by CRC, her grandmother died at 34 years old from FAP followed by CRC, her great-grandmother died at 60 years old from FAP followed by CRC. A 52-year-old mother is alive and has no complaints (Fig. 1).

It is also known that the patient underwent right-sided thoracotomy with resection of upper mediastinal tumor at 6 months old (desmoid fibroma).

Considering above-mentioned symptoms, the patient turned to the Vladimir Regional Clinical Hospital in 2016. Examination revealed tumor of the right hemisphere and cerebellar vermis, occlusive hydrocephalus with periventricular edema. Emergency right-sided ventriculoperitoneal bypass surgery was performed in September 2016. After that, the patient was referred to the Burdenko Neurosurgery Center in December 2016. Resection of a tumor of cerebellar vermis and the right cerebellar hemisphere was carried out with intraoperative neurophysiological monitoring.

Histological conclusion: morphological pattern and immunophenotype are more consistent with anaplastic ependymoma (WHO grade III).

Postoperative period was uneventful. The patient was discharged on the 7^th postoperative day.

In January 2017, contrast-enhanced MRI of the brain revealed residual areas of contrast enhancement along the periphery of postoperative bed, numerous small areas in the right cerebellar hemisphere without progression. Considering these MRI data, radiotherapy has been conducted for the period from March to April 2017 (Primus LUE with multi-petal collimator, photon energy 6 MeV). There were 30 courses with a single dose of 2 Gy, total dose of 60 Gy. Clinical deterioration was observed after this procedure (adynamia, aphasia, inability to move independently). In this regard, the patient was hospitalized to the Department of Neurosurgery of the Vladimir Regional Clinical Hospital in May 2017. Examination revealed occlusive hydrocephalus with periventricular edema. Emergency let-sided ventriculoperitoperitoneal bypass surgery was performed (Medtronic system with a medium pressure Burr Hole pump). Treatment was followed by clinical improvement (recovery of motor activity and speech).

However, the patient still complained of periodic discharge of blood and mucus with stools and tendency to constipation. In August 2018, colonoscopy was performed in the Suzdal and multiple colon polyps were diagnosed. Therefore, FAP was first diagnosed. The patient was referred to the Ryzhikh Coloproctology Center.

General condition was satisfactory at admission. The patient was in mind, sluggish, adynamic, answered the questions monosyllabically, with pauses, moved in a wheelchair. She was comprehensively examined.

Colonoscopy revealed large creeping neoplasm of soft-elastic consistency in lower ampullar part of the rectum immediately after the anal canal. Neoplasm was localized within left anterior semicircle and occupied up to 1/2 of the colon lumen.

During endoscopic examination, endoscope was passed up to the cecum and into small bowel for 10 cm. Small bowel lumen was intact, wrinkles were small. There were about 130 adenomatous polyps 0.5—1 cm in all parts of the colon. A large circular pink villous tumor with a length of 6—7 cm was found in the upper ampullar part of the rectum. A large creeping villous tumor with a length of up to 5 cm involving anal canal was determined in the lower ampullar part of the rectum. Soft-elastic neoplasm was localized within left anterior semicircle and occupied up to 1/2 of the colon lumen (Fig. 2a, b).

Contrast-enhanced CT of the abdominal organs: ventriculoperineal bypass grafts were determined in the abdominal cavity, distal end of one shunt was found in the left subphrenic space, distal end of the other — in the right mesogastrium (Fig. 3a, b).

Molecular genetic examination revealed APC gene mutation c.2730_2737del8.

Thus, the following diagnosis was made considering all these data:

Primary diagnosis: Familial adenomatous polyposis, classic form. APC gene mutation c.2730_2737del8. Turcot syndrome (Anaplastic ependymoma of cerebellar vermis and the right cerebellar hemisphere). Gardner syndrome (Desmoid tumor of the upper mediastinum). Villous tumors (2) of the rectum up to 6 cm.

Concomitant diagnosis: cerebellar syndrome, oculomotor impairment syndrome, severe cognitive impairment. Undifferentiated epilepsy. Bilateral endocrine-inactive adrenal tumors. Operations: 1) right-sided thoracotomy with resection of upper mediastinal desmoma (1990); 2) resection of cerebellar tumor (12.2016); 3) ventriculoperitoneal bypass (2016, 2017). State after previous radiotherapy with total dose of 60 Gy (03-04.2017).

Colectomy with abdominal-anal resection of the rectum and Brook’s ileostomy was made in December 2018 considering the diagnosis of FAP. Postoperative period was uneventful.

Morphological data: multiple tubular (mainly) and tubulo-villous adenomas with mild epithelial dysplasia, great number of aberrant crypts and microadenomas with mild epithelial dysplasia are observed throughout the colon mucosa. A large circular rectal tumor is a villous adenoma with mild and focal moderate epithelial dysplasia. Morphological conclusion: morphological pattern of familial adenomatous polyposis (Fig. 4).