In the Archives of Pathology & Laboratory Medicine, Behdad and Owens presented the case study of a patient with gastrointestinal symptoms who was incidentally diagnosed with systemic mastocytosis

A 32-year-old female presented with intermittent diarrhea and abdominal pain that started 3 months earlier. Her physicians initially suspected inflammatory bowel disease and conducted an upper gastrointestinal endoscopy and colonoscopy. The upper endoscopy did not reveal any abnormalities; the colonoscopy, however, revealed nodular mucosal irregularities with reduced vascular pattern throughout the colon.

The findings did not typically correlate with Crohn’s disease or ulcerative colitis. The patient’s surgeons proceeded to collect biopsy specimens from the small intestine and colon. 

The biopsy results revealed lamina propria expansion, minimal intestinal crypt architectural distortion, and a rare focus of active cryptitis. These findings are typical for inflammatory bowel disease in a quiescent phase. Her physicians also noticed a population of spindled cells with oblong, ovate nuclei, pale cytoplasm, and inconspicuous nucleoli upon histological evaluation. 

Read more about systemic mastocytosis etiology 

“These cells stained strongly with a c-KIT immunohistochemical stain, confirming the morphologic impression of mast cells,” Behdad and Owens wrote. “Additionally, the mast cells were immunohistochemically positive for tryptase and aberrantly expressed CD25.” 

The patient was hence diagnosed with systemic mastocytosis with gastrointestinal involvement. 

Analyzing Gastrointestinal Pathology 

The symptoms experienced by a patient with systemic mastocytosis can be rather heterogeneous; some patients are asymptomatic, while others experience multiorgan dysfunction/failure. 

“Most of the symptoms can be attributed to the release of vasoactive substances and other inflammatory mediators and include flushing, hypotension, dyspepsia, diarrhea, abdominal pain, or musculoskeletal pain,” Behdad and Owens wrote. 

With regards to gastrointestinal pathology specifically, around 60% to 80% of patients with systemic mastocytosis are affected. This means gastrointestinal symptoms represent a major cause of morbidity among patients with systemic mastocytosis. The release of mediators and mast cell infiltration in the gut is typically the cause of gastrointestinal lesions. 

The observation of gastrointestinal pathology in patients with systemic mastocytosis has led some scientists to implicate mast cell involvement in diarrhea-predominant irritable bowel syndrome. Diarrhea-predominant gastrointestinal pathology with symptomatic improvement upon treatment with an inhibitor of mast cell mediator release and histamine receptor antagonists has now been termed “mastocytic enterocolitis.” 

One of the difficulties of correctly associating gastrointestinal symptoms with systemic mastocytosis is that systemic mastocytosis is typically far down in the list of differential diagnoses. In the case study described above, the patient’s physicians initially suspected inflammatory bowel disease as the cause of her gastrointestinal abnormalities. 

Read more about systemic mastocytosis diagnosis 

When gastrointestinal symptoms manifest, physicians typically first suspect the ingestion of contaminated food. If that is ruled out, they typically move on to investigate Helicobacter pylori involvement. If that is also ruled out, endoscopy and colonoscopy can reveal if the patient has ulcerative colitis, Crohn’s disease, or a tumorous growth. 

“In patients with isolated or predominant [gastrointestinal] symptoms, the identification of mastocytosis can be very difficult as symptoms overlap with many other more common [gastrointestinal] diseases such as gastroesophageal reflux, Helicobacter pylori gastritis, peptic ulcer, inflammatory bowel syndrome, inflammatory bowel disease, celiac disease, and even carcinoma, which need to be ruled out,” Zanelli and colleagues summarized in Cancers. 

Histological Features 

In the case study presented, it was the characteristic histological features of systemic mastocytosis that led the patient’s physicians to diagnose her with the disease. 

Typically, endoscopy may reveal mucosa with nodules, thickened folds, or pigmented areas. Even if mucosal biopsy specimens do not show a substantial concentration of mast cells, a patient’s gastrointestinal symptoms can still be caused by the systemic effects of released mediators. 

Doyle and colleagues in The American Journal of Surgical Pathology recommend that multiple biopsies be taken at various sites throughout the gastrointestinal tract. Because gastrointestinal pathology in systemic mastocytosis can be multifocal, collecting biopsy samples at various locations increases the odds that pathologists might detect abnormalities that aid diagnosis. 

“In general, the histologic differential diagnosis of mastocytosis in the [gastrointestinal] tract is limited,” Doyle et al wrote. 

Perhaps a more consequential development is when systemic mastocytosis is incidentally diagnosed upon the exploration of gastrointestinal disease instead of the other way around. This is what occurred in the case study presented. When systemic mastocytosis is established from gastrointestinal mucosal biopsies, they can serve as an alternative to bone marrow biopsy. 

It is important to note that around half of patients with systemic mastocytosis do not have endoscopic abnormalities. Hence, the severity of gastrointestinal disease does not necessarily correlate to the severity of systemic mastocytosis. Studies reveal that some patients with gastrointestinal pathology have indolent systemic mastocytosis, while others have a more aggressive form of the disease. 

“Our findings also demonstrate the wide spectrum of disease involvement in [gastrointestinal] mucosal biopsies, particularly those cases with minimal involvement by mastocytosis, which may only be recognized by the presence of more obvious involvement in other biopsies and/or a clinical history of mastocytosis, in conjunction with aberrant expression of CD25,” Doyle et al wrote. 

Because gastrointestinal disease is not the primary feature of systemic mastocytosis, simply recognizing that the two can be related can aid physicians in arriving at a correct diagnosis and administering treatment accordingly. 

References

Behdad A, Owens SR. Systemic mastocytosis involving the gastrointestinal tract: case report and reviewArch Pathol Lab Med. 2013;137(9):1220-1223. doi:10.5858/arpa.2013-0271-CR

Doyle LA, Sepehr GJ, Hamilton MJ, Akin C, Castells MC, Hornick JL. A clinicopathologic study of 24 cases of systemic mastocytosis involving the gastrointestinal tract and assessment of mucosal mast cell density in irritable bowel syndrome and asymptomatic patientsAm J Surg Pathol. 2014;38(6):832-843. doi:10.1097/PAS.0000000000000190

Zanelli M, Pizzi M, Sanguedolce F, et al. Gastrointestinal manifestations in systemic mastocytosis: the need of a multidisciplinary approachCancers (Basel). 2021;13(13):3316. doi:10.3390/cancers13133316