Clinical Case Summary

Langerhans cell histiocytosis (LCH) is a rare condition caused by the clonal proliferation of bone-marrow derived antigen presenting langerhan cells. Its incidence is prevalent in the pediatric population with 4-5 million cases per year in adults the incidence is even more rare with approximately 1-2 million cases per year. It can manifest as a unifocal, multifocal single-system, or even multi-system disease, which creates a true medical challenge in its diagnosis and management. LCH most commonly presents with osseous lesions, but is exceedingly rare in the GI tract with the prevalence limited to only a handful of cases–-approximately less than 30 in the English literature till date to the best of our knowledge. We present a 44-year-old Caucasian female with a past medical history significant for GERD, type 2 diabetes mellitus, gastroparesis, essential hypertension, and a family history of colon cancer in the patient’s maternal and paternal uncles was referred for evaluation of chronic abdominal pain and diarrhea via colonoscopy. Prior to the procedure, the patient admitted to chronic diarrhea and intermittent but self-resolving left lower quadrant abdominal pain, but otherwise denied any hematochezia, constipation, tenesmus, nausea or vomiting with oral intake, unintentional weight loss, fevers, chills, or recent illnesses. Colonoscopy showed erythema throughout the sigmoid colon, ulceration in the transverse colon, and a single sessile 2 mm polyp was found in the rectum. Transverse colon biopsy revealed a submucosal infiltrate of Langerhans cells with indented nuclei and pale eosinophilic cytoplasm and admixed inflammatory cells. Furthermore, immunohistochemical staining revealed cells strongly positive for S-100 protein, CD-1a, and CD56–confirming Langerhans cell histiocytosis. Our case is another rare presentation that contributes to the understanding of this highly variable disease and possible treatment with further clinical studies and trials.

References

-Image of the transverse colon biopsy with histiocytic infiltrate in the lamina propria
-Image of the CD-1a+ immunohistochemical staining

Clinical Case Summary

Enteropathy-associated T-cell lymphoma (EATL) is an intestinal tumour of intra-epithelial lymphocytes. It is most often, but not always, associated with celiac disease. It is a rare disease with an annual incidence rate of 0.5-1 per million. EATL Type I is a large cell lymphoma which is associated with celiac disease. EATL type II consists of small to medium-sized cells and has no known association with celiac disease.
The patient, a 60 year old female, presented with chronic diarrhea. Colonoscopy showed a small 3mm sessile polyp in the descending colon which was removed via cold snare polypectomy (insert pic). The colon mucosa was normal and random biopsies were taken. Histology did not have any abnormal features. The polyp histology showed lymphoid aggregates with a focal area of increased intraepithelial lymphocytes. This was inconclusive and not diagnostic of microscopic colitis. Celiac serologies were negative. The patient continued to have persistent diarrhea with electrolyte imbalances, and extensive evaluation was done. CT did not show any masses nor pancreatic lesions. Stool studies for bacterial infections, parasites were negative. She was treated presumptively for Small Intestinal Bacterial Overgrowth (SIBO) with rifaximin. However, her diarrhoea continued. Repeat colonoscopy was done two months later which showed mild erythema in the ascending colon (insert pic), and a 2mm transverse colon polyp and removed via polypectomy (insert pic). Random biopsies were again taken. Histology now showed monomorphic epitheliotrophic T-cell lymphoma (Insert pic).
Patient was diagnosed with aggressive monomorphic EATL type II. Although bone marrow examination did not show any evidence of lymphoma, she was managed with chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone.
This case highlights the importance of the approach to chronic diarrhea, and although rare, repeat endoscopy should be considered to ensure no worsening of lymphocytosis.

References

Delabie et al., Enteropathy-associated T-cell lymphoma: clinical and histological findings from the International Peripheral T-Cell Lymphoma Project. Blood 2011; 118 (1): 148–155.
Jolanda etal., Enteropathy associated T-cell lymphoma and its precursor lesions, Best Practice & Research Clinical Gastroenterology, Volume 24, Issue 1, 2010, Pages 43-56

Clinical Case Summary

A 52-year-old woman, already suffering from diabetes insipidus diagnosed 6 years earlier and on therapy with desmopressin, presented to our gastroenterology department for a routine screening colonoscopy after a positive FOBT. The patient did not complain of gastrointestinal symptoms. Subepithelial nodular formations with apical ulceration in the transverse colon were found. Pathological analysis revealed pseudonodular aggregates in the lamina propria composed of histiocytic elements (CD163+) morphologically compatible with Langerhans cells (CD1a+, Triptase-, MPO-, S100-/+, pan CK-). The diagnosis was confirmed by immunohistochemical analysis for Langherin, which turned positive.
Further outpatient evaluation with endocrinologist was scheduled, after which disease staging was initiated. Initially, PET-CT with FDG, EGDS, and thyroid FNA were performed, all of which were negative for additional disease localizations. Bone marrow aspiration and bone biopsy showed no infiltration, negative flow cytometry, and no evidence of V600E BRAF mutation in molecular biology.
A reassessment of the cerebral area was then performed by MRI, which revealed an expansive formation in the suprasellar region measuring 9x11x9 mm, compatible with an infundibulo-hypothalamic localization of the disease.
The patient then underwent gynecological evaluation, which revealed a vulvar lesion subjected to biopsy, with histological and immunohistochemical characteristics (CD1a+, S100+, Langherin+) consistent with the pathology.
A systemic therapy cycle was initiated for two months with vinblastine in 5 intravenous administrations of 3 mg, 6 mg, and then 8 mg weekly, along with a course of oral deltacortene 75 mg.
At the 2-month follow-up cerebral MRI after the end of therapy, the expansive posterior suprasellar formation appeared unchanged.
Twelve months after the previous colonoscopy, the lesions in the transverse colon previously described were no longer visible.

Clinical Case Summary

Introduction: Primary colorectal lymphoma is a rare condition. The incidence has varied from 0.1% to 0.9% of all colorectal malignancies in many series[1]. MALT lymphomas arise from mucosa-associated lymphoid tissue and can involve various organs, including the gastrointestinal tract, lung, salivary glands, thyroid, and unusual sites, such as the dura[2]. The most common site for MALT lymphoma is the stomach. MALT lymphoma of the colon and rectum is the least common gastrointestinal location.
Case presentation: A 63-year-old female presented to the Digestive Department of our hospital for iron deficiency anemia , weight loss, abdominal pain and positive FIT testing. The patient had no previous medical history. Physical examination upon admission showed that the patient was pale with lower abdominal tenderness, blood pressure and heart rate were normal. Laboratory results showed iron deficiency anemia hemoglobin 8.4g/dl, MCV:77.3 fl, MCH:22.6 pg, MCHC: 29.4 g/dl, positive FIT Testing. Colonscopy was done and revealed small area of rectal erythema by white light endoscopy, NBI showed a clear margin with a dark brown background and enlarged branch-like vessels on the surface of the lesion. The lesion was classified as NBI international colorectal endoscopic (NICE) type 3 and Japanese NBI expert team (JNET) type 3 ,multiple biopsies were taken and stained for CD20, BCL-2, CD3, CD5, CD10, BCL-6, CD23 and Ki-67, picture support diagnosis of low grade extranodal marginal zone lymphoma of mucosa associated lymphoid tissue. Upper endoscopy was palnned which was completely normal apart from GERD grade A. Abdominal CT with contrast showed mild area of rectal thickening 2.5 x 2 cm. The treatment options was discussed by multidisclipinary team and the patient refered to our department again for EMR which was done safetly with complete excision of the mucosal lesion. She was subjected for colonscopic follow up after 6 months.

References

1. Tevlin R, Larkin JO, Hyland JM, O'Connell PR, Winter DC. Primary colorectal lymphoma - A single centre experience.Surgeon 2015; 13: 151-155 [PMID: 24694573 DOI: 10.1016/j.surge.2014.01.002]
2. Wöhrer S, Kiesewetter B, Fischbach J, Müllauer L, Troch M, Lukas J, Mayerhoefer ME, Raderer M. Retrospective comparison of the effectiveness of various treatment modalities of extragastric MALT lymphoma: a single-center analysis.Ann Hematol 2014; 93: 1287-1295 [PMID: 24633660DOI: 10.1007/s00277-014-2042-z]

Clinical Case Summary

Introduction: Heterotopic gastric mucosa (HGM) is not uncommon throughout the gastrointestinal (GI) tract, nevertheless its presence in the lower GI is considered as a rare entity. The purpose of this study is to report a clinical case of HGM located in the rectum, which was presented with intermittent bleeding. The medical history of the patient and the way was treated are presented.
Case presentation: A 40-year-old male patient with an unremarkable medical history presented to the outpatient clinic suffering from anal pain, accompanied with intermittent rectal bleeding. At colonoscopy, a solitary flat elevated lesion with central depression, approximately 2 cm in size, was identified in the lower part of the rectum. Histological examination of the biopsy specimen showed heterotopic gastric mucosa while Giemsa stain was positive for Helicobacter Pylori (HP). First-line treatment for HP eradication including a 14-day course of proton pump inhibitor (PPI), amoxicillin, clarithromycin and metronidazole was administered. One month after therapy was completed, the patient underwent a Urea Breath Test (UBT) and an HP antigen stool examination, which were both negative. Meanwhile, the symptoms had been resolved. Unfortunately, the patient never returned to follow the standard procedure of proper clinical and endoscopic re-evaluation.
Conclusion: HGM can be either congenital, as a result of an error in the differentiation of the endodermal stem cells during organogenesis, or acquired, as a metaplasia during the repair of damaged epithelium. When located in rectum, HGM can be presented with symptoms such as bleeding, abdominal or anal pain. Moreover, complications such as ulcer and even adenocarcinoma have been reported. Although endoscopic or surgical resection is considered as the radical therapy of the HGM in rectum, administration of PPIs, inhibitors of histamine-receptors or HP eradication treatment, in cases HP is present, is effective in short-term symptoms relief.

References

1) Iacopini F, Gotoda T, Elisei W, Rigato P, Montagnese F, Saito Y, Costamagna G, Iacopini G. Heterotopic gastric mucosa in the anus and rectum: first case report of endoscopic submucosal dissection and systematic review. Gastroenterol Rep (Oxf). 2016 Aug;4(3):196-205. doi: 10.1093/gastro/gow006. Epub 2016 Apr 21. PMID: 27103738; PMCID: PMC4976682.
2) Devereaux CE, Devereaux RG. Heterotopic gastric mucosa of the rectum with a review of the literature. J Clin Gastroenterol. 1994 Jul;19(1):41-5. doi: 10.1097/00004836-199407000-00011. PMID: 7930432.
3) Chrysanthos, N. & Anagnostopoulou, Evagelia & Daskalaki, Anna & Patsavela, Stamatia. (2015). Images of the Month. The American journal of gastroenterology. 110. 498. 10.1038/ajg.2014.251.
4) Chen WG, Zhu HT, Yang M, Xu GQ, Chen LH, Chen HT. Large heterotopic gastric mucosa and a concomitant diverticulum in the rectum: Clinical experience and endoscopic management. World J Gastroenterol 2018; 24(30): 3462-3468 [PMID: 30122884 DOI: 10.3748/wjg.v24.i30.3462]

Clinical Case Summary

Diffuse nodular lymphoid hyperplasia (DNLH) of the gastrointestinal tract is a rare benign disease characterized by multiple polypoid nodules, associated with inborn errors of immunity (IEI) such as common variable immunodeficiency (CVID) and infections like Giardia lamblia. To date, there are few cases reported in Southeast Asia. We present a patient in Singapore with DNLH associated with CVID.
A 39-year-old man presented with one year of intermittent diarrhoea with nocturnal episodes, associated with abdominal pain. Colonoscopy revealed a normal colon, but there were multiple diminutive polyps in the terminal ileum (TI). Histology showed mild chronic inflammation with lymphoid aggregates, without any microorganisms. Magnetic resonance enterography did not identify any sizeable polyps within the small bowel, which would have led to further evaluation for gastrointestinal lymphoma.
Stool studies, sent on a subsequent bout of diarrhoea, returned positive for Giardia lamblia. He was treated with metronidazole but his diarrhoea persisted. On probing further, he had a history of recurrent rhinosinusitis and febrile illnesses since childhood, prompting further laboratory studies which showed a normal full blood count, erythrocyte sedimentation rate of 11mm/hour, and hypogammaglobulinemia. A diagnosis of CVID was made and he was initiated on regular intravenous immunoglobulin (IVIG) replacement with resolution of his diarrhoea.
Surveillance colonoscopy three years later demonstrated prominent lymphoid follicles from the ascending to rectosigmoid colon, in addition to the TI. Histology was consistent with DNLH without dysplasia. He remains well and asymptomatic on regular IVIG.
In summary, as DNLH is associated with IEI and parasitic diseases, it is important to evaluate for these diseases upon diagnosis. DNLH is also associated with gastrointestinal lymphoma that may warrant surveillance, though the clinical course is unclear and there are no guidelines for surveillance.

References

ALBUQUERQUE. A. Nodular lymphoid hyperplasia in the gastrointestinal tract in adult patients: A review. World J. Gastrointest. Endosc., 2014, 6 (11) : 534-540.
Illustrative material in final poster
1. Endoscopic image of prominent lymphoid follicles in colon and terminal ileum
2. Pathological image of terminal ileum biopsy demonstrating lymphoid aggregates

Clinical Case Summary

8 years boy, presented with a spontaneous entero(colo)-cutaneous fistula for last 6 months. The patient had a history of colonic perforation at 1 year of age, twice spontaneous gastric perforations at 1.5 years of age, entero-cutaneous fistula at 2.5 years of age, colonic perforation, and reopening of anastomosis at 6 years age. For these complaints, he underwent a total of 7 abdominal surgeries. The child also had recurrent fever, skin infections, and oral ulcers along with neutropenia, mild anemia, high CRP, and ESR. Bone marrow aspiration and biopsy were normal. Upper gastrointestinal endoscopy was normal; colonoscopy showed patchy erythema, whitish scar areas, and no ulcers except for hepatic flexure where a large fistula was communicating to the skin. Colonic biopsies suggested chronic inflammation without granulomas.
Whole exome sequencing showed two mutations: 1. Heterozygous TNF-AIP3 gene suggestive of Autoinflammatory syndrome, familial, Behcet-like 1 (autosomal dominant). 2. The homozygous HAX1 gene is suggestive of severe congenital neutropenia (autosomal recessive).
Clinically the patient had features of both the disorders. The patient was started on cotrimoxazole prophylaxis and infliximab (IFX) which led to complete fistula closure within 6 months with gain in 10 cm height. Due to low neutrophils, he was also given G-CSF. A small fistula recurred after 9 months. Investigations showed low IFX levels with very high antibodies to IFX. After due consideration and consent the patient was given steroids followed by tapering and Adalimumab was added. After 6 months of treatment, the fistula has healed completely.
Conclusion: There is a need to do early genetic analysis in unusual cases. Both the above-mentioned mutations are very rare and unfortunately, our index patient suffered from both, which made our choice of treatment challenging. The role of biologicals can be extended to newly diagnosed rare disorders if pathogenic mechanisms are similar to IBD.

References

Berteau F, Rouviere B, Delluc A, Nau A, Le Berre R, Sarrabay G, Touitou I, de Moreuil C. Autosomic dominant familial Behçet disease and haploinsufficiency A20: A review of the literature. Autoimmun Rev. 2018;17:809-815.