Figure 2.198 Granulomatous gastritis pattern. The granulomatous gastritis pattern is best appreciated at low power. In this spectacular example, numerous large granulomata are seen deep in the mucosa (arrowheads). This patient had a history of sarcoidosis, was status post pancreatoduodenectomy for pancreatic adenocarcinoma, and was on chemotherapy. Consequently, this patient had numerous potential causes for this nonspecific injury pattern.
CHECKLIST: Etiologic Considerations for the Granulomatous Gastritis Pattern
Crohn Disease
Sarcoidosis
Infection (Helicobacter, Mycobacterial, Fungal)
Medication
Foreign Body Reaction
Nearby Neoplasm
Vasculitis (Best Assessed on Resection Specimens)
Common Variable Immunodeficiency
Chronic Granulomatous Disease
Granulomata are collections of epithelioid histiocytes admixed with lymphocytes and plasma cells (Fig. 2.198). They are occasionally accompanied by foreign body-type giant cells (Figs. 2.199–2.205). The morphology of the granulomata can offer some clues to a specific etiology based on subtle histologic features: poorly formed granulomata are commonly seen in Crohn disease, tight granulomata are common in sarcoidosis, and uniformly sized granulomata with caseating necrosis suggest an infection. Unfortunately, these subtle histologic clues are not reliable enough for a confident etiologic diagnosis. Indeed, the granulomatous gastritis pattern may be one of the best examples of a patterns based approach because the identical injury pattern can be seen with an expansive list of varied clinical settings. In the largest series of the granulomatous gastritis pattern (n = 71 patients), most cases showed a single granuloma and most granulomas (64%) were located in the antrum. Careful clinical correlation determined an association with Helicobacter (92%, n = 64), Crohn disease (52%, n = 37), foreign body reaction (10%, n = 7), neoplasms (7%, n = 4), sarcoidosis (1%, n = 1), Whipple disease (1%, n = 1), and vasculitis (1%, n = 1).165 Similar associations have been reported by others.166,167 The granulomatous gastritis pattern can also be a red flag to consider rare immune-mediated diseases such as common variable immunodeficiency (CVID)98 and chronic granulomatous disease (CGD),168 making it worthwhile to evaluate for apoptotic body prominence and paucity of plasma cells (CVID) and a careful chart review for clinical stigmata of CGD, particularly in the pediatric setting. Some suggest that idiopathic granulomatous gastritis is rare, if it exists at all, and should be surmised only if a thorough and exhaustive exclusion of all possible diagnoses have been confidently excluded.166 This leaves the pathologist with a fair amount of detective work, including careful scrutiny of the background mucosa, a detailed clinical chart review, and often a conversation with the clinician to frame this peculiar finding in its appropriate clinicopathologic context. Acid fast bacillus (AFB) and Gomori methenamine silver (GMS) special stains are worthwhile to exclude mycobacteria and fungal organisms, respectively, in all cases of granulomatous gastritis, although most are negative.
Figure 2.199 Granulomata. Higher power of the previous case (Fig. 2.198). A granuloma is a collection of epithelioid histiocytes admixed with lymphocytes and plasma cells. As seen here, epithelioid histiocytes are characterized by “slipper-shaped” nuclei or nuclei with oblong, thin nuclei (arrowheads). Special stains for Helicobacter, fungi (GMS), and mycobacteria (AFB) were negative.
Figure 2.200 Granulomata, foreign body reaction. In this classic example of a granuloma, the epithelioid histiocyte collection is surrounded by lymphocytes, plasma cells, and scattered foreign body-type giant cells (arrowheads). This patient had a history of a gastrostomy tube placement and mucosal erythema was endoscopically identified in association with the instrument tip. In the absence of other contributing factors, iatrogenic injury was the likely nidus for the associated granulomatous inflammation. Special stains for microorganisms were negative.
Figure 2.201 Granulomatous gastritis pattern, sarcoidosis. This case originated from a patient with sarcoidosis. Special stains for microorganisms were negative.
Figure 2.202 Granulomatous gastritis pattern, Crohn disease. Although the prior cases feature spectacular teaching examples of the granulomatous gastritis pattern, in actuality, gastric granulomata are usually much harder to identify. This more typical example originated from a patient with a long-standing history of upper-tract Crohn disease. A small, poorly formed granuloma is identified (arrowhead) in a background of active chronic gastritis.
Figure 2.203 Granulomatous gastritis pattern, Crohn disease. On higher power, the epithelioid appearance of the histiocytes is better appreciated (arrowhead), as is the background active chronic inflammation. Special stains for microorganisms were negative, suggesting this injury pattern was most likely a manifestation of upper-tract Crohn disease.
Figure 2.204 Granulomatous gastritis pattern, Crohn disease. This case features another sneaky granuloma (arrowhead) in a patient with a history of upper-tract Crohn disease. This type of subtle granuloma is best appreciated on scanning magnification: at low power, a “hole”-like appearance is due to local displacement of the neighboring gastric pits. A background of active chronic inflammation is also seen.
Figure 2.205 Granulomatous gastritis pattern, Crohn disease. It would be easy to miss this tiny granuloma (arrowhead) with such prominent background active chronic inflammation: granulomata are typically best seen at lower power (compare to previous figure). Special stains for microorganisms were negative.
FAQ: What is the significance of an isolated foreign body giant cell in the stomach (Fig. 2.206)?
Answer: An isolated foreign body giant cell is abnormal but this finding is etiologically nonspecific. Deeper sections may be worthwhile to see if the foreign body giant cell is part of a deeper granuloma. Such cases are signed out descriptively with a note addressing the most likely possibilities after careful chart review; for example, in the context of a patient with established sarcoidosis, this isolated finding is most likely compatible with the history of sarcoidosis, whereas in patient status post chemotherapy for widely metastatic carcinoma, a medication injury would be favored, assuming infection has been excluded. For the clinician, an isolated foreign body giant cell can sometimes raise concerns for Crohn disease, in which case correlation with the clinical history and biopsies of the terminal ileum, right colon, left colon, and rectal biopsies may be worthwhile, in the appropriate clinicopathologic setting.
Figure 2.206 An isolated foreign body-type giant cell in a background of active chronic gastritis (arrow). Although an isolated foreign body giant cell is abnormal, it does not imply a specific etiology.
FAQ: What is the best approach for a case with a vaguely granuloma-like focus that is exhausted on deeper sections?
Answer: Beware of crushed gastric epithelium, cauterized muscularis mucosae, and scattered histiocytes that can look vaguely like epithelioid granulomata in suboptimal specimens. In questionable cases, deeper sections and a CD68 immunostain can be helpful, if the indicated focus is present on deeper sections. In cases in which collections of histiocytes are seen but the histiocytes lack both the epithelioid morphology and granuloma type architecture, “focal histiocyte aggregates” or “focal histiocyte collections” are satisfactory to document the findings without glorifying these ambiguous findings with the clinically charged term “granuloma”.