*Corresponding author:Vivian Regina Guzela, Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, Departamento de Gastroenterologia, Av. Dr. Enéas de Carvalho Aguiar, 255. Cerqueira César – São Paulo, SP 05403-000, Brazil
How to cite this article:Vivian R G, Carlos W S J, Dewton d M V, Lucas F S, Sérgio C N , et al. Rectal Cancer in Common Variable Immunodeficiency:
A Case Report. Adv Res Gastroentero Hepatol, 2020;14(5): 555900. DOI: 10.19080/ARGH.2020.14.555900.
Introduction:Common variable immunodeficiency (CVID) is a primary immunodeficiency related predominantly to immunoglobulin (Ig) G and IgA deficiency with or without changes in IgM levels. Other immunological pathways may also be altered, which makes this pathology extremely heterogeneous. The main manifestations include predisposition to severe infections, development of autoimmune diseases and greater susceptibility to the development of neoplasms, especially lymphomas and gastric cancer. There are reports of colorectal and anal cancer in this population, very variable in terms of histology (lymphomas, squamous cell carcinoma), but little is found about rectal adenocarcinoma concomitantly with CVID and ulcerative colitis (UC). The objective of this case report is to demonstrate the unusual association between colorectal cancer in a young patient presenting CVID.
Case presentation:A 31-years-old patient complained of an increased number of bowel movements associated with tenesmus and hematochezia and presence of mucus within the feces. As a personal history, she had been diagnosed with CVID and UC since she was 14 years old. Since then she is treated with intravenous immunoglobulin monthly and sulfasalazine, with clinical response. At the current physical examination, splenomegaly was noted and in rectal examination, a mass adhered to medium rectum was touched. The colonoscopy had revealed enanthem and ulcers, three rectal polyps and an ulcerative infiltrative lesion in the middle rectum. Biopsies identified nonspecific chronic colitis, high-grade tubular adenoma, high-grade tubulo-villous adenoma, high-grade tubular adenoma with focus of intramucosal adenocarcinoma and invasive tubular adenocarcinoma of the rectum, respectively. Staging showed no distant lesions and pelvic resonance suggested a T2N0 rectal neoplasia. The patient was then submitted to videolaparoscopic rectosigmoidectomy with total excision of the mesorectum and the pathological staging confirmed the radiological result. The patient is currently being followed by oncology, immunology, and colon and rectal surgery, asymptomatic after the re-introduction of the previous medications.
Conclusion:CVID may predispose to colorectal diseases, including IBD´s and neoplasms like rectal cancer, so our article suggests these patients should be considered for clinical and endoscopic screening for the entire gastrointestinal tract disorders and not only for gastric cancers.
Keywords:Rectal cancer; Common variable immunodeficiency; Ulcerative colitis; Inflammatory bowel disease
Abbreviations: CVID: Common Variable Immunodeficiency; Ig: Immunoglobulin; UC: Ulcerative Colitis; IBD: Inflammatory Bowel Disease; IUIS: International Union of Immunological Societies; ESID: European Society for Immunodeficiencies; 5-ASA: Aminosalycilates Derivatives; mm: Millimeter; cm: Centimeter; MRI: Magnetic Resonance Imaging; CT: Computerized Tomography
There are about four hundred known monogenic inborn errors of immunity that can present various phenotypes such as susceptibility to infections, development of neoplasms, allergies, autoimmune and inflammatory diseases. The International Union of Immunological Societies (IUIS) had developed a classification based on the presentation of these diseases, in order to facilitate diagnosis and broaden consensus among publications .
CVID is the most common symptomatic primary immunodeficiency, predominantly related to immunoglobulin G and A deficiencies, with or without variations of IgM levels . About one third of patients may also have other immune defects including T cells alterations . The European Society for Immunodeficiencies (ESID) establishes diagnostic criteria designated in Table 1. CVID is the most heterogeneous among primary immunodeficiencies and may manifest in both children
and adults. The B lymphocyte count may be normal, low or absent.
Only 20% of CVID patients have genetic mutations identified and
are no longer considered in the spectrum of this disease, but as a
specific immunodeficiency, since CVID is by definition of unknown
Treatment is based the immunoglobulin replacement and, in
more severe cases, allogeneic bone marrow transplantation may
be considered . Infectious manifestations include mainly otitis,
sinusitis and pneumonia, which may evolve with bronchiectasis.
Infectious diarrhea by agents such as Giardia, Salmonella and
Campylobacter jejuni may also occur and arthritis, notably caused
by Mycoplasma, is also suggestive .
Another common manifestation present in up to one third
of patients are autoimmune diseases, such as thrombocytopenic
purpura and hemolytic anemia. In the gastrointestinal tract, celiac
disease may be present as well as inflammatory bowel diseases
(6 to 10% of the patients), with biopsy showing typical reduction
of plasma cells, besides villous atrophy . In addition to these
diseases, CVID patients may also present Sjögren´s syndrome,
systemic lupus erythematosus, vitiligo, alopecia, diabetes (type 1)
and Guillain-Barré syndrome.
The general incidence of cancer in CVID is about 10% and
usually occurs between the fourth and sixth decade of life, with
a risk between 5 to 12 times higher than in the population .
The most common neoplasms are B-cell lymphomas and gastric
cancer. Non-Hodgkin´s and Hodgkin lymphomas, pancreatic
neuroendocrine tumor, chronic myeloid leukemia, breast cancer
and papillary thyroid carcinoma had been described until now .
Lymphomas can represent up to 40% of malignancies in patients
with CVID and non-Hodgkin without association with Epstein-Barr
virus infection. Gastrointestinal tract tumors may occur at varying
frequencies in this subpopulation (0,48% to 14,6%), represented
in 72% of the cases as gastric cancer, where Helicobacter pylori
infection and pernicious anemia play important role .
A meta-analysis of 2016 describes colorectal involvement as
22% of gastrointestinal malignancies in CVID, but descriptions
commonly do not detail the prevalent histological results. Some
case reports had described intestinal involvement lymphomas,
colonic neuroendocrine tumors and anal squamous cell
carcinomas [5-7]. So, in this case report, we emphasize the
importance of thinking about gastrointestinal involvement in CVID
patients, considering that this group may have two risks factors
do development of colorectal cancers: the immunological disease
by itself and the IBD continuous inflammatory commitment.
A caucasian female patient, 31-year-old, from São Paulo –
Brazil, complained of tenesmus, hematochezia and mucus within
the stool, with a frequency of 4 evacuations daily associated with
a weight loss of 13 pounds in the last 4 months. As a personal
history, ate age 11, she had started do develop recurrent
infections, especially sinusitis and pneumonia, as well as episodic
liquid diarrhea. At 14-years-old, the diarrhea had become bloody
and accompanied with a severe abdominal pain, in addition to
worsening of the severity of infectious conditions, despite the
emergence of arthralgia. After being diagnosed with bronchiectasis
and mild pancolitis with enanthema, the patient was screened for
immunodeficiencies and hypogammaglobulinemia was detected.
Conduct by the immunologist, she received the diagnostic of CVID
and UC. At this time, the treatment prescribed included monthly
infusion of immunoglobulin and 5-ASA orally (sulfasalazine),
achieving satisfactory clinical response, normalization of the
bowel habits and reduction of the frequency and severity of the
Over the following years, she had presented four episodes of
hematemesis, diagnosed as esophageal varices and chronic liver
disease. With the medical control of the portal hypertension and
the endoscopic band ligation and sclerotherapy to the varicosal
disease, the patient remained asymptomatic until her thirtieth
birthday, having performed her last colonoscopy five years before
the beginning of the symptoms with no inflammation involvement.
In relation to her family history, there were no cases of polygenic,
autoimmune or even neoplastic diseases.
On physical examination, the patient has adequate nutritional
status, the abdomen showed a Traube space massive on percussion,
besides a palpable mass in the left hypocondrium, suggesting
splenomegaly. In the proctological examination, in addition to a small perianal tag skin, in the rectal digital examination was
possible to notice a mass adhered 8 cm above the anal verge,
occupying two third of the circumference of the middle rectum,
with the presence of blood in the glove. After the emergence of
the symptoms, the patient was asked to make general laboratory
tests and the only altered results were a pancytopenia and a
carcinoembryonic antigen of 6,7mg/dL. The colonoscopy revealed
normal terminal ileum, diffuse colon enanthema, punctate ulcers
with fibrin in the ascending colon, three subpediculate polyps
(10 to 12mm) in upper and middle rectum (Figure 1 & 2) and
an ulcerative infiltrative lesion in the middle rectum, with a
diameter about 4 cm (Figure 3). Pathological anatomy identified
nonspecific chronic colitis, high-grade tubular adenoma, highgrade
tubular villus adenoma, high-grade tubular adenoma with
focus of intramucosal adenocarcinoma (the specimen margins
were free of neoplasia) and an invasive tubular adenocarcinoma,
Pelvic magnetic resonance imaging (MRI) showed a rectal
lesion, above the peritoneal reflection, with 3,5 centimeters
in diameter, occupying 60% of the circumference, invading
the muscular, without compromising the mesorectal layer and
without lymph node enlargement (Figure 4). Abdominal and
pelvic computerized tomography (CT), in addition to the lesion
described, revealed a spleen with 21 centimeters, signs of chronic
liver disease and portal hypertension (Figure 5) and the chest
tomography did not find any nodular lesions.
The patient underwent laparoscopic abdominal
rectosigmoidectomy with total mesorectal excision, as the initial
stage was T2N0M0 and the lesion coincident with the limit of
peritoneal reflection (Figure 6 & 7). The histological conclusion was
a moderately invasive carcinoma of 2,6 cm, pT2pN0, with thirteen
lymph nodes unaffected. The postoperative course continued
without any complications and, despite the mayor susceptibility,
there were no infectious diseases, with diet reintroduction on the
first postoperative day. Currently, the patient has been followed
by a multidisciplinary team (immunologist, oncologist and
colon and rectal surgeon) for eighteen months without signs of
cancer relapse. 5- ASA derivative was prescribed again, as well as
immunoglobulin and the beta-blocker to the portal hypertension
and until now the patient remains asymptomatic.
This case report illustrates the rare occurrence of rectal
adenocarcinoma in a patient with CVID. It is well known that
these patients most commonly develop autoimmune diseases
such as UC and this condition may predispose to colorectal cancer
after some years of chronic inflammation, however there are
no publications about this evolution in patients with a primary
immunodeficiency. This case may suggest that in some groups like
this, gastrointestinal cancer screening should not only be done to
the upper tract, with upper endoscopy, due to the mayor incidence
of gastric cancer. Careful attention should be paid to complaints
related not only to colorectal cancer, but also to IBD, proposing
an early diagnose and assertive treatment, with a follow-up with
smaller intervals between the endoscopic examinations, since
the malignancies seems to develop early in these patients. Some
reports have referred to intestinal involvement lymphomas,
colonic neuroendocrine tumors and anal squamous cell carcinoma
[5-7], but until this article writing nothing was found about rectal
adenocarcinoma in the indexed publications.
In conclusion, we suggest that patients with CVID should
undergone early endoscopic screening of the upper and
low gastrointestinal tract, aiming to diagnose IBD or other
predisposing malignant conditions.
This case report was submitted to the ethical committee
“Comitê de Ética para Análise de Projetos de Pesquisa”
(CAPPESQ) of the Hospital das Clínicas – Faculdade de Medicina
da Universidade de São Paulo and to Plataforma Brasil, with
approval. The informed consent signed by the patient is available
Data sharing is not applicable to this article as no datasets
were generated or analysed during the current study, because it is
a case report in which all relevant exams and patient´s information
is available in the article itself.