Multiple venous malformations in the left colon and rectum: a long-standing case managed conservatively and an update of current literature

Abstract

Venous or cavernous malformations of the colon or rectum are a rare cause of lower gastrointestinal bleeds. It has been previously described as a diffuse cavernous haemangioma which was thought to be a benign vascular tumour. It mainly affects the rectosigmoid area of the gastrointestinal tract and is most common in children and young adults. Misdiagnosis is common with patients averaging a total of 19 years delay to this final diagnosis. We report a case of a 65-year-old patient who presented with occult, painless rectal bleeding and prior to this presentation, had been managed variously as colitis and angiodysplasia. This article aims to delineate the updated classification of this disease, principal clinical clues to aid the diagnosis while discussing patient treatment options and potential challenges faced in patient management.

Background

Venous or cavernous malformations (VMs) can present with symptoms ranging from recurrent painless rectal bleeding to massive haemorrhage causing life threatening haemodynamic instability.¹ It was first elucidated in 1839 however, its pathogenesis is not fully understood²; it is suspected to be derived from inherent defects of growth factor and endothelial cells pertaining to mesodermal tissue.³ It is thought that 80% of these malformations of the rectum and sigmoid colon are cavernous (extensive), with capillary malformations occupying the remainder.⁴ VMs are known to mimic other conditions notably carcinoma, haemorrhoids and proctitis. This has led to up to 80% of cases experiencing unnecessary surgical procedures and a delay in diagnosis.⁵ The range in diagnostic delay is said to be from 2 months to 70 years.⁴ Our aim in presenting this case is to raise awareness of an uncommon condition which can results in considerable morbidity if unrecognised.

Case presentation

A 65-year-old white man was referred by his primary physician with occult, painless rectal bleeding. There was no history of any change in bowel habit, nausea, vomiting or stool consistency. He had similar problems for 22 years, and he was originally admitted to hospital for several weeks with a tentative diagnosis of angiodysplasia or colitis. He had since that time been on 1.2 g of Asacol (mesalazine) daily and prophylactic iron tablets. A tapering dose of prednisolone was also prescribed by his primary physician during this period with the intention of reducing any potential inflammation. He has never had any significant medical ailments apart from musculoskeletal injuries. Family history revealed that his sister had a haemangiopericytoma adjacent to the bladder and uterus excised and his mother suffered with ischaemic heart disease in her 60s. His alcohol consumption was within the recommended 14 units a week and was an ex-heavy smoker (up to 40 cigarettes a day). Abdominal examinations revealed a soft, non-tender abdomen and no peripheral stigmata of any gastrointestinal disease. A digital rectal examination was unremarkable.

Investigations

Routine laboratory investigations showed normal haemoglobin (150 g/L) and ferritin levels (124 µg/L). Being above 50 years of age with unexplained rectal bleeding however prompted referral for direct colonoscopy. There were multiple cystic swellings of the rectal mucosa up to 15 cm, containing serous fluid (figure 1), with grossly abnormal background mucosa which was purple/black suggesting submucosal petechiae or abnormal vasculature (figure 2A,B). The purplish discolouration extended to 40 cm, with normal mucosa above this from the proximal descending colon to the caecum. There was no evidence of mucosal inflammation. Biopsy on the wall of the protrusion revealed a fluid filled cyst and this led to excessive bleeding requiring haemostatic clip. Rectal and sigmoid biopsies were normal. An initial suspicion of pneumatosis coli was excluded by a normal plain film abdominal X-ray (AXR) which showed no abnormal bowel gas patterns and no free intraperitoneal gas however did reveal multiple pelvic phleboliths. A CT angiogram of abdomen and pelvis revealed conventional and patent visceral arteries with no venous or arterial abnormalities relating to the GI tract. There was however circumferential thickening of the middle and lower rectum with multiple calcified foci scattered throughout the abdomen (figure 3A,B). Twenty-two years previously at his original presentation: flexible sigmoidoscopy had been noted to have very abnormal-looking rectal mucosa and had been treated with mesalazine for presumed ulcerative colitis. From that time, he had continued to have intermittent rectal bleeding which were occasionally severe, but he had not required blood transfusion or repeat admission to hospital until the recent presentation.

Figure 1.

Rectal mucosa with cystic fluid-filled swellings of the mucosa.

Figure 2.

(A and B) Rectosigmoid and sigmoid mucosa with abnormal vascular pattern and purplish discolouration due to submucosal venous malformations.

Figure 3.

(A) CT axial reconstruction—rectal wall thickening with intramural and mesenteric phleboliths (arrow). (B) CT sagittal reconstruction—rectal wall thickening with intramural and mesenteric phleboliths (arrows).

Differential diagnosis

The appearance was initially considered to be either pneumatosis coli, melanosis coli, rectal varices or a vascular malformation of some sort. On the basis of his CT scan, the possibility of a submucosal tumour of the rectum was considered, but the endoscopic appearance and histology did not suggest this. The plain AXR did not show typical changes of pneumatosis coli and he did not have any stigmata of chronic liver disease nor radiological evidence of portal hypertension on the CT scan. Histology ruled out melanosis and inflammatory bowel disease. After a literature search, the long benign history coupled with the characteristic endoscopic appearance and phleboliths on CT were considered in keeping with a diffuse cavernous haemangioma (DCH) or the recently updated classification of this disease—a venous malformation.

Treatment

The patient was managed conservatively. The iron tablets and mesalazine were discontinued because of this update in diagnosis. Advice was given to the patient to seek medical attention if rectal bleeding was getting conspicuously worse or if he started having symptoms of anaemia.

Outcome and follow-up

Six months passed, and the patient presented to his community doctor with per rectal bleeding, lasting around 6 weeks. He passed large volumes of fresh blood and clots around 7 to 8 times daily at its worst. He denied having any perianal pain, diarrhoea and systemic symptoms. Haemoglobin fell to 102 g/L; however, it quickly recovered on re-initiation of the iron tablets. He did not require blood transfusion or intravenous iron. At clinic review 18 months after the presentation, he remains well, with no further bleeding, normal bowel habit, and stable haemoglobin at 155 g/L, with ferritin at 23 ug/L. He declined a further flexible sigmoidoscopy. The patient reiterated his desire to avoid any surgical intervention and was content with the possibility that this could mean he has similar unpredictable episodes in the future.

Discussion

The term ‘haemangioma’ is mainly used due to clinical familiarity with the term but in the truest sense, it is actually a cavernous malformation.^6–8 The more recent classification (revised in May 2018) by the International Society for the Study of Vascular Anomalies), classifies cavernous haemangiomas/malformations as venous malformations which in essence also aims to distinguish malformations from haemangiomas.⁹ Histologically, a haemangioma has a high endothelial cell turnover and it is usually present 6–8 weeks after birth.¹⁰ Haemangiomas also tend to have a proliferative phase for a few years and usually spontaneously involute whereas venous malformations (previously classified as cavernous haemangiomas) tend to grow in proportion to body size.^{10 11} Intestinal vascular malformations are also usually present at birth and have a normal endothelial cell turn over. They can be further classified as capillary malformations, cavernous (either diffuse and expansive or localised) or a mixed pattern.⁴ These lesions can be present in the skin, spinal cord, brain and bone as part of syndromes such as blue rubber bleb nevus syndrome, Osler-Weber Rendu syndrome, Proteus Syndrome, Kasabach-Merritt syndrome and Klippel-Trenaunay-Weber syndrome.¹² Despite these associations of haemangiomas and vascular malformations, only 2% have GI manifestations with these syndromes, with cutaneous lesions aiding diagnosis for most of these syndromes.⁴

A literature search shows around 350 reported cases of VMs of the colon with a female predominance of around 3:1.^{4 13} Anaemia (>50%) and painless lower gastrointestinal bleeding (>75%) are the most common presenting symptoms.^{1 14} Intravascular coagulation within the tumour leading to platelet destruction and coagulation factor consumption may lead to the acute, chronic or intermittent bleeding seen in VMs.¹⁵ Rectal bleeding could be ongoing from childhood however around 10% of patients are completely asymptomatic.¹ It could also present as bowel obstruction (17%) where localised lesions could act as a nidus for intussusception while larger masses cause mechanical luminal obstruction and may invade surrounding viscera causing abdominal or pelvic discomfort.^{1 16} Stool consistency is a poor marker as patients can present with both diarrhoea and constipation.¹⁷

A recurring theme with VMs is misdiagnosis, and this seems to be a significant cause of mortality and morbidity for these patients. In our case, it was thought to be proctitis or possibly angiodysplasia. In the literature, other cases were treated with unnecessary haemorrhoidectomies, polypectomies, transfixation and sclerotherapy for rectal varices secondary to portal hypertension or given mesalazine for colitis.¹⁷ The patient’s old case notes and previous imaging were no longer available, and we speculated that preceding diagnoses may have been due to concealment of typical endoscopic manifestations from bowel wall ischaemia as a consequence of multiple thrombo-embolic occurrences in these dilated vessels. These ischaemic changes may lead to erosions and indistinguishable oedematous ulcerations, mistaken for inflammatory changes seen in proctitis or ulcerative colitis.¹⁸ The cost of treatment with Asacol for the 22 years was significant.¹⁹ The numerous superficial vascular ectasias seen on colonoscopy could have been mistaken as angiodysplasia previously. Aetiologically, they may also suggest a mixed capillary, cavernous malformation or even a consequence of imbalances in pro-angiogenic and antiangiogenic factors from regional tissue hypoxia.²⁰

In terms of clinical diagnosis, the typical endoscopic appearance (once recognised) and the radiological findings of multiple phleboliths proved vital. Imaging modalities (plain radiography, sonography, CT scan, MRI, angiography and colonoscopy) ruled out alternative diagnoses. Multiple hyaline/calcified thrombi (phleboliths) are commonly seen in the pelvis in VMs due to venous stasis. Doppler ultrasound may show a low velocity flow (as opposed to high velocity flow in arteriovenous malformations) or thrombosis with heterogeneous hypoechoic lesions.²¹ MRI is better than CT scans for image clarity and multiplanar functions however both help define the extent of the lesion (T2-W sequence with fat suppression on MRI is best for this) and will be necessary prior to any surgical intervention.²² They may reveal classical irregular thickening of bowel wall and venous malformations will show hypointensity on T1-W and hyperintensity on T2-W imaging.²² Colonoscopy is believed to be the gold standard as it clearly depicts luminal extension and morphology of the malformation. Engorged lesions that appear bluish may be seen and most authors suggest not to biopsy such lesions as at least 1 in 4 of these patients are at risk of severe blood loss.²³ There is a theoretical risk of progression to Disseminated Intravascular Coagulation (DIC) after trauma or unnecessary surgery due to intravascular coagulopathy leading to moderate thrombocytopenia, hypofibrinogenaemia and raised D-dimer.

Management of venous malformations of the gut is challenging, but definitive treatment is surgery. A modified low anterior resection which involves a pull through transection and coloanal anastomosis is best.²⁴ It is sphincter saving and associated with normal urinary and sexual function.²⁵ Compared with other sphincter saving procedures, it is associated with less operating times and lower intraoperative blood transfusions.¹⁷ Sclerotherapy, cryotherapy, embolisation and thermoablation (electrocautery) may only provide brief symptom control.¹⁴ The recent use of medical therapies like celecoxib, thalidomide, propranolol and bevacizumab have been employed due to their inhibition of Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) pathways along with vasoconstriction and are showing early promise.^{26 27} Factors such as patient preference, malformation morphology and locale and symptom severity ultimately determine the best treatment course.¹³ Collectively, these were the reasons our patient was managed conservatively.

Learning points.

• The absence of mucosal inflammation makes inflammatory bowel disease exceedingly unlikely.

• A diagnosis for venous or cavernous malformations (VM) should be considered in patients with long-standing and unexplained bleeding with typical appearance at endoscopy and phleboliths/mucosal thickening on CT scan.

• Plain X-ray, sonography, CT scans, MRIs and endoscopy provide definite pathognomonic evidence and if venous malformation is suspected, mucosal biopsy should be avoided.

• The most effective treatment to date is a pull-through transection and coloanal anastomosis. A modified low anterior resection can also be considered.

• Use both cavernous haemangioma and venous malformations when searching literature.