Mastocytosis Colitis in 54 year old woman: A rare case report

Introduction: Mastocytosis is a rare disorder occurring due to neoplastic clonal proliferation of mast cells accumulating in one or more organ systems. Systemic mastocytosis is generally diagnosed after the second decade of life, reported male-to-female ratios range from 1:1 to 1:1.5. Case description : A 54-year-old woman came complaining weakness and diarrhea for the last 2 months. Symptoms are watery stools for 2-4 times a day and nausea. Physical examination found that the body temperature was 37.6 0 C, tachycardia, increased bowel sounds, and tenderness on stomach. An endoscopic examination was performed with results: transverse colon appears with polyps with a size of 3 mm, with a mosaic pattern of mucosa. The mucosa of the ascending colon and caecum also appears to be a mosaic pattern. Biopsy was sent for histopathological examination. Morphological features show significant increase of eosinophils & mast cells, differentially diagnosed with Mastocytosis colitis, Eosinophilic colitis, systemic mastocytosis with GI involvement. Methodology : Descriptive study of the case report type, data were obtained from the patient's record. Discussion and Conclusion : To rule out the differential diagnosis, an immunohistochemical examination and clinical correlation were performed. On histopathological examination, microscopic features showed the proliferation of mast cells in the aggregate only in the colon, without any other systemic manifestations, an increase in the number of mast cells >20/HPF was found in the colonic mucosa. The staining of CD117 on cells in the superficial (1/3 top) of the lamina propria suspected of being a mastocyte, supporting mastocytosis colitis. no cólon, sem outras manifestações sistêmicas, um aumento no número de mastócitos >20/HPF foi encontrado na mucosa colônica. A coloração de CD117 em células na superfície (1/3 superior) da lâmina própria suspeita de ser um mastócito, suportando a colite mastocitose morfológicas muestran un aumento significativo de eosinófilos y mastocitos, diagnosticados diferencialmente con mastocitosis colitis, colitis eosinofílica, mastocitosis sistémica con afectación gastrointestinal. Metodología: Estudio descriptivo del tipo reporte de caso, los datos se obtuvieron de la historia clínica del paciente. Discusión y Conclusión: Para descartar el diagnóstico diferencial, se realizó un examen inmunohistoquímico y correlación clínica. En el examen histopatológico, las características microscópicas mostraron la proliferación de mastocitos en el agregado solo en el colon, sin otras manifestaciones sistémicas, se encontró un aumento en el número de mastocitos> 20/HPF en la mucosa colónica. La tinción de CD117 en células en la superficie (1/3 superior) de la lámina propia sospechosa de ser un mastocitos, apoyando colitis por mastocitosis. Microscopic examination on biopsy tissue from ascending colon shows; surface epithelium, crypts, lamina propria & mucosal muscle on one tissue. Crypts generally do not show distorsion with rack of test & daisy flower pattern. Multiple infiltrative focus of eosinophilic PMN cells to crypt epithelium (in accordance with eosinophilic cryptitis). Lamina propia contains blood vessels with telangiectatic pattern & prominent inflammatory cells. On superficial part (upper ⅓ ) shows lamina propria with dense band-like distribution, consisting of cells with morphologically coiled-round nucleus, surrounded by moderate amount of pale-clear cytoplasm, mastocyte cell impression observed under conventional H&E staining, some mixed w ith mature plasma cells. On lower ⅔ of lam ina propria, abundant eosinophilic PMN distributed along with plasma cells & lymphocytes.


Introduction
Mastocytosis is a rare disorder with uncertain incidence number and gives a heterogeneous / varied picture, making diagnosis difficult, not solely based on histopathological features, but correlation with clinical and other investigations is needed to determine systemic involvement, which is characterized by accumulation of abnormal mast cells in various tissues.
While skin mastocytosis (localized skin form) is a classic presentation occurring in children, and tends to heal spontaneously in pediatric cases. One case study estimates that 1 in 1000 people in America have this condition. Mastocytosis generally affects men and women in equal amounts. This disease may begin in childhood or adulthood. (Cancer.net, 2022;Reggiania, 2015).
During puberty, systemic mastocytosis (SM) frequently occur in adults, marked with: mast cell infiltration to extracutaneous organs (e.g, bone marrow, liver, spleen, digestive tract, lymph nodes); this form of SM is progressive and doesn't have the tendency to regress. These two forms of mastocytosis are considered as myeloproliferative disorders. (Reggiania, 2015).
Mastocytosis occurs due to mast cell clonal neoplastic proliferation which accumulates in one or more organs. This is marked by abnormal mast cell infiltrates, which often contain multifocal clusters or cohesive aggregates. The most common symptoms are abdominal pain (avg 51%) followed by diarrhea (avg 43%) and nausea and vomiting (avg 28%). About 50% of children affected show typical skin lesions before the age of 6 months. Skin mastocytosis is much less common in adults than children. The cause of skin mastocytosis in children might be due to embryogenesis and early mast cell formation. Systemic mastocytosis is generally diagnosed after the second decade of life, and reported men-women ratio of 1:1 to 1:1.5. (Horny, 2017;Lee, 2008).
Based on studies in mice, it has been proposed that mammalian mast cells may originate from at least two different sources during embryonic development and that mast cells present in the skin at birth are gradually replaced by different populations as the individual matures. The presence of defects in the mast cell population that originates in the embryonic yolk

Methodology
This is a descriptive study from a case report. In general, case study research is centered on a phenomenon, which is described as detailed as possible (Yin, 2017;Pereira et al, 2018). The analytic description of the clinical case being presented in chronological order, and literally reviewed using a scientific database. Our research ethics committee did not review any ethical clearance for the case report that was already discussed at the clinicopathological conference and approved by the clinician, patient, and pathologist. Following ethical principles, the patient consent to disseminating the data and displaying images of her case for academic purposes. Informed consent form was signed willingly.

Case Description
A 54-year-old woman came to the ER at Sanglah Central General Hospital complaining of weakness and digestive problems for the past 2 months. She suffered an increase in bowel movements frequency approximately 2-4 times a day, her stools are sometimes watery, and sometimes accompanied with nausea. Diarrhea is not accompanied with abdominal pain before or even after stool passing. Patient also complained of weight loss of approximately 8 kg in 2 months. Her previous medical history was only checking herself up to a general medical clinic and received medicines for indigestion and diarrhea.
There are no previous chronic illnesses recorded.
On physical examination, the body temperature was sub-febrile with 37.6c, tachycardia, increased bowel movements, and tenderness in the epigastric area. Then, an endoscopic (colonoscopy) exam was done and results were as follows; anusrectum looks normal, sigmoid colon is normal, descending colon is normal, a 3 mm polyp with mosaic pattern mucosa in transverse colon was identified, whilst terminal ileum looks normal.
On ascending colon, biopsy was performed for histopathological examination. On 24/12/2022, a sample of 3 specimens in 10% NVF solution with patient's identity, Each of the specimens are 1-2 mm long, gray-white color as seen on  From this microscopic examination on Figure 2, its concluded; Morphology shows lesion of colon mucosa from endoscopic biopsy associated with significantly increased eosinophils and mast cells, maybe diagnostically differentiated with Mastocytosis colitis, Eosinophilic colitis, Systemic mastocytosis with GI involvement. Further histochemical examination is required to ensure the lesion is mastocytosis colitis. Microscopic photos of ascending colon mucosa lesion from endoscopic biopsy. A&B) biopsy tissue limited to ascending colon mucosa layer (H&E 40x). C) consist of surface epithelium, crypts, lamina propria & mucosa muscle, without image distortion with rack of test & daisy flower like pattern (H&E 100x). D) multiple infiltrative eosinophilic PMN cells to crypts epithelium (in accordance to eosinophilic cryptitis), lamina propria contains dense distribution of band like cells indicating mastocyte, and on lower ⅔ of lamina propria shows rich distribution of eosinophilic PMN mixed with plasma cells and lymphocyte (H&E 400x). Source: Authors.
On May 10th 2021, immunohistochemical examination was done to the biopsy tissue. Figure 3 is showing the results as follows: Immunohistochemical staining for CD117/c-kit on ascending colon tissue biopsy, shows strong positively stained mast cells on cell membrane and cytoplasm. CD117 staining on superficial cell parts (upper ⅓) of lamina propria suspected as mastocyte, therefore supporting the diagnosis of mastocytosis colitis.

Discussion
Systemic Mastocytosis (SM) is a rare disease, heterogenic and progressive, marked with abnormal proliferation and mast cell infiltration on multiple organs. Mastocytosis variants are identified mainly through pathological examination, disease distribution, and clinical manifestation, including GI tract. GI tract symptoms occur on 14-85% patients with systemic mastocytosis. (Horny et al, 2017;Reggiania et al, 2015).
Around 50% of children affected show typical skin lesions before 6 months old. Skin mastocytosis occur very rarely in adults compared to children. Systemic mastocytosis generally diagnosed after second decade of life with 1:1 to 1:1.5 ratio of men to women. (Horny et al, 2017 ;Cestells et al, 2021).
In the reported case, a 54 year old woman with GI tract manifestation without skin involvement.
In the reported case, the patient complained of fatigue, and GI tract disturbances since around the last 2 months. She experienced increased defecation of 2-4 times a day, stools are sometimes runny and accompanied with stomach ache. Patient also complained about weight loss of around 8kg in the last 2 months. Endoscopic findings as shown by Figure 4 on patients with mastocytosis affecting GI tract range from subtle abnormalities to severe ulceration. Mucosa erythema, nodularity-polipoid, ulceration, or strictures are commonly found depending on GI tract location involved. (Srivastava, 2016).
In this case, the endoscopic findings are normal anus-rectum, normal sigmoid colon, normal descending colon, a polyp of 3mm on transverse colon with mosaic pattern, on mucosa of ascending colon and caecum also show mosaic pattern, meanwhile on terminal ileum no abnormalities were found. atrophy may be seen. (Reggiania et al, 2015). SM is determined by major and minor criteria, a minimum of 1 major and 1 minor criteria, or at least 3 minor criteria met. (Horny et al, 2017;Sristava, 2016). ○ Serum total tryptase persistently > 20 ng/ml, unless an associated myeloid neoplasm is present, in which case this parameter is invalid.
On histopathological examination, a microscopic picture of mastocytosis will show mast cell infiltration in the lamina propria with round or spindle cell nucleus morphology and moderate pale to clear cytoplasm. As explained on Figure 5, mast cell infiltration density varies, fine infiltrates usually show a band-like appearance under the surface epithelium in the mucosal layer. A biopsy of the nodular lesion shows a denser confluent infiltrate and clearly resemble a lymphoproliferative disorder.
In the reported case, Mast cell proliferation abnormalities were found in aggregates only in the colon, without any clinical skin manifestations such as urticaria pigmentosa or other systemic signs such as hematological abnormalities.
Histopathological examination found an increase in the number of mast cells >20/HPF in the colonic mucosa, accompanied by symptoms of chronic diarrhea. Therefore, this case is more suitable to be diagnosed as mastocytosis colitis.

Differential diagnosis:
1. Eosinophilic Colitis (EC); very rare, only a few cases have been reported since 1979. The diagnosis of EC depends on histopathology identifying an excess of eosinophils. Clinical presentations include abdominal pain, diarrhea (bloody or bloodless), and/or weight loss. EC in primary cases may be associated with other atopic conditions. Colonic eosinophilia may also occur secondary to helminthic infections (eg pinworm / helminthic, hookworm), inflammatory bowel disease, autoimmune diseases (eg scleroderma, Churg-Strauss syndrome), celiac disease, and drug reactions. Normal eosinophil counts vary based on the anatomic location of the GI tract. In the duodenum, it is defined as <10 eosinophils per 1 large visual field (HPF) in pediatric patients and <19 eosinophils/HPF in adults. Therefore, microscopic examination showing >10 eosinophils/HPF in children and >20 eosinophils/HPF in adults has been established as the threshold for meeting both diagnostic criteria for mucosal eosinophilic gastroenteritis. However, in the caecum, the threshold should be set at a higher value, up to 40 eosinophils/HPF has been suggested as a normal value at this location. While the colon is up to 16/HPF in pediatric patients, up to 50/HPF in adults. Furthermore, when evaluating eosinophil counts, environmental factors need to be observed and considered: eosinophil counts will be higher during peak allergy seasons and among populations living in the southern regions of the US. (Sunkara et al, 2019).

Systemic mastocytosis with GI involvement;
Based on the diagnostic criteria described above, SM can be determined by major and minor criteria, there must be at least 1 major and 1 minor criteria, or at least 3 minor Because the criteria for systemic mastocytosis and its variants are not met according our references, the reported case is more suitable for mastocytosis colitis. Clinical correlation and multidiciplinary approach also needed (Zanelli M, 2021).

Prognosis
In this case report, it is important for diagnosis accuracy especially on conditions with unresolved chronic diarrhea.
This mastocytic colitis has no specific therapy, symptomatic treatment is necessary. Treatment with H1 and H2 histamine antagonists may be considered with varied results. Prognosis can be poor if aggressive clinical manifestations occur. (Sristava, 2016).

Conclusion
Mastocytosis is a rare disorder and may occur due to neoplastic clonal proliferation of mast cells that accumulate in one or more organ systems. One of the most common is gastrointestinal (GI) manifestations that can occur in up to 85% of patients with systemic or focal mastocytosis, with manifestations such as; abdominal pain, diarrhea, nausea, vomiting, and bloating. It is generally diagnosed after the second decade of life, and reported male-to-female ratios range from 1:1 to 1:1.5.
Mastocytosis with skin manifestations is much less common in adults than in children. Endoscopic findings in patients with mastocytosis involving the GI tract macroscopically generally reveal mucosal erythema, nodularity-polypoid, ulceration, or stricture. On histopathological examination, the microscopic picture shows proliferation of mast cells in the aggregates only in the colon, without any other systemic manifestations, an increase in the number of mast cells >20/HPF was found in the colonic mucosa. The staining of CD117 on cells in the superficial (upper 1/3) lamina propria suspected mastocyte, then may Research, Society andDevelopment, v. 11, n. 13, e11111332410, 2022 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v11i13.32410 9 support the diagnosis of mastocytosis colitis. Management and prognosis in this case are closely related to the accuracy of diagnosis, therapy with H1 and H2 histamine antagonists can be considered with varied results. Prognosis can be poor if aggressive clinical manifestations occur.
We hope this article will provide better insight for this special disease and we suggest routine GI checkup such as GI tract endoscopy on systemic or focal mastocytosis patients, mainly with GI symptoms. Suspicions to this disease should yield more aggressive diagnostic techniques since early detection would improve the outcome. More reports should be brought to light further improving our understanding to the disease.