• A 59-year-old woman presented with dyspepsia and epigastric pain for a few weeks.

• Upper endoscopy revealed minimal gastric mucosal irregularity.

• A set of biopsies was taken.

Clinical History

IAP Congress – JordanMimics of Neoplasia in the GI tract

Diffuse process of the lamina propria

Expansion of LP by an eosinophilic cellular infiltrate

Infiltrate present round inconspicuous nuclei & granular / fibrillar eosinophilic cytoplasm

Differential Diagnosis of an Infiltrative Process

InfectiousMAIWhipple(Malakoplakia)

Foreign materialXanthomaGlycolipid storage diseasesGranular cell tumorNeoplastic (epithelial)

Gastric AdenocarcinomaMetastatic CA (Breast)

Hematopoeitic diseasesLymphomaNK Cell enteropathyLymphomaRosai DorfmannRussell body gastritis

??

AFB

MAI

Tropheryma Whipplei

Whipple’s disease

CD68

Gastric Xanthoma

GI Manifestations of Systemic Diseases

CD68Gaucher’s disease

Granular cell tumor

Signet Ring Cell Gastric Cancer

Alcian Blue

Poorly cohesive gastric cancer

CDX2

Metastatic lobular breast CA, Malignant melanoma ought to be ruled out

NK-Cell enteropathy

CD56 Granzyme CD3

NK-Cell enteropathy

Russell Body Gastritis

Crystal Storing Histiocytosis

Histiologic Characteristicsof Crystal Storing Histiocytosis

• Infiltration of lamina propria by large, oval, polygonal & occasionally, spindle cells.

• Abundant eosinophilic cytoplasm and small eccentric nuclei.• Cytoplasm is packed w/ elongated, rectangular, needle-shaped/

fibrillary crystalline inclusions.• Inclusions are approximately 5–20 nm long and are frequently

arranged in parallel arrays.

Histopathology 2007, 51, 114–137; Am J Surg Pathol 2018;42:1317-1324; J Pathol Transl Med 2017; 51: 341-351; Clin J Gastroenterol 2013:6:237–242

Histopathology 2007, 51, 114–137; Am J Surg Pathol 2018;42:1317-1324; J Pathol Transl Med 2017; 51: 341-351; Clin J Gastroenterol 2013:6:237–242

• Monoclonal immunoglobulins are phagocytosed by histiocytes & crystallized when broken down by lysosomes. The acidophilic crystals grow and accumulates in RER

– Most cases are Kappa restricted [more degradation resistant than lambda light chain?]

CD79a IgG• Inclusions may not react with Kappa/Lambda IHC

– altered antigenicity?– insufficient Ag quantities?

• ISH also negative because of lack of intact mRNA

Transmission EM appearance of CSH

Intracytoplasmic crystals – some free and and others packed in bundles showing a fibrillary appearance in dilated endoplasmic reticulum

Histopathology 2007, 51, 114–137; Am J Surg Pathol 2018;42:1317-1324; J Pathol Transl Med 2017; 51: 341-351; Clin J Gastroenterol 2013:6:237–242

Crystal Storing Histiocytosis

• Rare condition• Systemic or described in isolation in:

– Lung, – Thymus– Lymph nodes– Kidney, – Thyroid & Parotid glands– Cornea – Stomach

~10% of CSH are not associated with B lymphoproliferative disorders

• Immune mediated disease: Rheumatoid arthritis, Crohn’s disease• Systemic mastocytosis

• Also– Chronic clofazimine– Charcot-Leyden crystal associated [eosinophilic colitis; cutaneous

hypereosinophilic Sd.]

Endoscopic appearance of gastric CSH

• Incidence of 8% in gastric lymphoma• Also associated with:

– H. pylori infection– thymic lymphoma– multiple myeloma– Sjogren’ syndrome