Case 4 -
Crystal-storing Histiocytosis and Associated Small B-cell Lymphoma with Plasmacytic Differentiation
Alyssa M. Krasinskas
University of Pittsburgh
Click on each slide thumbnail image for an enlarged view
- The presence of abundant, large, eosinophilic
cells in the lamina propria of the stomach is unusual.
- Finding these cells in a
nodule is even more unusual.
- The differential diagnosis for such cells is quite
broad and includes reactive, infectious, immunologic, iatrogenic and neoplastic processes.
A 59 year-old female presented to our gastroenterologist from an outside institution with
the history of a "gastric deformity/subepithelial tumor." The in-house endoscopy showed a single 8 mm
nodule in the gastric fundus. It "had a yellow hue, central depression, and was firm when probed." By
EUS, this lesion appeared to originate from within the muscularis propria. The lesion was biopsied and
essentially removed with cold jumbo forceps.
Case 4 - Figure 1
Very low power view of the mucosal biopsy.
Case 4 - Figure 2
Low power magnification of the gastric mucosa showing a chronic gastritis and eosinophilic cells within the lamina propria. An immunostain for H. pylori was positive.
Case 4 - Figure 3
Medium power view.
At low power, a band-like infiltrate expands the upper half of the lamina propria of the oxyntic
mucosa and lymphoid aggregates are present. At higher magnification, the lamina propria contains a
lymphoplasmacytic inflammatory cell infiltrate and numerous eosinophilic cells. The eosinophilic cells
are large with abundant cytoplasm. The nuclei are slightly larger than plasma cell nuclei and some are
ovoid while others are angulated. At even higher magnification, the eosinophilic cytoplasm appears to
contain coarse, refractile granules. Special stains were performed. An immunohistochemical stain for
Helicobacter pylori was positive. Acid fast and PAS-D stains were negative. The eosinophilic cells were
negative for cytokeratin, S-100, CD138 and immunoglobulin heavy chains; these cells were positive for
CD68 and weakly expressed kappa light chain. The background lymphoplasmacytic infiltrate was also
characterized by immunohistochemical stains. The lymphoid aggregates co-expressed CD20 and CD43 and
showed kappa light chain restriction. The CD20 positive cells did not co-express CD5 or CD10.
Crystal-storing histiocytosis and
associated small B-cell lymphoma with plasmacytic differentiation.
Crystal-storing histiocytosis (CSH) is a rare condition in which crystalline material
accumulates within histiocytes. In classic CSH, the material that accumulates is crystalline
immunoglobulin. Most of these cases are associated with underlying lymphoplasmacytic neoplasms that
produce monoclonal light chains. As such, most cases involve the bone marrow and lymph nodes. However,
CSH can involve other organs, such as the lung, thyroid, kidney and soft tissue. Rare cases of
gastrointestinal involvement have been reported
and in one case report, the disease presented as
gastric polyps . When CSH occurs outside the setting of a lymphoproliferative disorder, it tends to
be associated with an underlying chronic inflammatory condition, such as rheumatoid arthritis or Helicobacter pylori infection; in these cases, the immunoglobulin crystals are
Two variants of CSH have been described in which the crystalline material is not
immunoglobulin: clofazimine-induced CSH 
and Charcot-Leyden crystal-associated CSH .
The formation of immunoglobulin crystals in CSH is thought to be the result of
overproduction of light chain protein. Kappa light chains have been identified in the vast majority of
cases of CSH that are associated with a lymphoplasmacytic neoplasm. Ultrastructurally, the crystalline
material within the histiocytes can appear either needle-like and fibrillary with regular periodicity or
rhomboid with angulated borders. The crystals tend to be membrane bound, often within dilated
endoplasmic reticulum. It is hypothesized that the crystals form as the result of specific
immunoglobulin mutations that prevent proper joining with heavy chains .
The presence of large, abundant, eosinophilic cells in the lamina propria of the stomach can pose a
diagnostic challenge. Based on the H&E findings in this gastric biopsy, the differential diagnosis
includes Russell body gastritis, granular cell tumor, infections (including atypical mycobacteria,
Whipple disease and histoplasmosis), clofazimine-induced histiocytosis and eosinophilic gastritis with
Charcot-Leyden crystal-associated CSH.
The main differential diagnosis in this case is localized Russell body
gastritis. In contrast to CSH, the eosinophilic cells in the lamina propria in cases of Russell
body gastritis are typically plasma cells. The eosinophilic inclusions (Russell bodies) expand the
cytoplasm of the plasma cells, they tend to be homogeneous with a smooth round contour, and they often
indent and push the nucleus to the very periphery of the cell. Ultrastructurally, Russell bodies are
round, smooth and membrane-bound (adjacent to the endoplasmic reticulum). Russell bodies are believed to
represent either mutated or possibly normal heavy chain immunoglobulins that are unable to be secreted or
degraded . While Russell bodies can be associated with lymphoplasmacytic neoplasms, they can also be
found in reactive plasma cells, such as in chronic gastritis. Rare Russell bodies are occasionally seen
in routine cases of chronic gastritis. However, when numerous Russell bodies are seen, the term "Russell
body gastritis" can be used . Most, but not all, cases of Russell body gastritis in the literature
are associated with Helicobacter pylori infection. Russell body gastritis
has also been reported to present as a tumor-like lesion , but due to the association of Russell
bodies with lymphoproliferative disorders, an underlying lymphoma needs to be excluded in such cases.
Granular cell tumors can arise anywhere in the gastrointestinal tract, with
the esophagus and colorectum being the most common sites. In the stomach, the antrum is the most common
location. Endoscopically, granular cell tumors can appear as yellow to white nodules or sessile
lesions. Histologically, these tumors are composed of nests and sheets of polygonal to elongated cells
with (as the name implies) granular cytoplasm, indistinct cell borders and small, oval nuclei. While
these cells can mimic histiocytes, they are of neural origin and stain for S-100; they are also PAS-D
Whenever collections of histiocytes are seen within the lamina propria of the gastrointestinal tract,
infectious etiologies should be excluded. Mycobacterium avium-intracellulare infection
can result in expansion of the lamina propria by numerous enlarged macrophages; an acid fast stain will
highlight the numerous intracellular organisms. Although often present in granulomatous inflammation,
can also be detected in scattered lamina propria macrophages of immunosuppressed individuals with
disseminated disease; a sliver stain will highlight the small yeast forms. While Whipple disease tends to affect the small bowel, one would not want to miss a case
just because only the stomach was biopsied. In addition to lamina propria macrophages, there may also be
dilated lymphatics and foamy or lipid-laden macrophages. A PAS-D stain will highlight substance (the
organisms) within the macrophages, but a confirmatory test, such as PCR or an immunostain for Tropheryma whippeli, should be performed.
There are two forms of CSH that are not related to the accumulation of immunoglobulin. One is Clofazimine-induced CSH . Clofazimine is used to treat leprosy and other
mycobacterial infections. A side effect of this medication is gastrointestinal toxicity. Patients with
Clofazimine-induced CSH can have lymphadenopathy and thickened bowel loops radiographically, resulting in
mucosal biopsies to exclude malignancy. Clofazimine crystals can accumulate within lamina propria
macrophages throughout the GI tract. In contrast to the immunoglobulin crystals described above,
Clofazimine crystals appear clear both on routine H&E stain and by electron microscopy;
interestingly, the crystals appear red on frozen sections. The macrophages are often admixed with plasma
cells and eosinophils.
Another form of CSH that is not associated with immunoglobulin aggregation is Charcot-Leyden crystal-associated CSH. The case that led to the description of this
entity involved the colon . The patient had eosinophilic colitis and associated polypoid lesions that
resulted from the accumulation of large collections of macrophages and eosinophils within the deep lamina
propria and superficial submucosa. The macrophages were filled with brightly eosinophilic needle-shaped
crystals. Ultrastructurally, the crystals were identical to Charcot-Leyden crystals (electron dense
needle-like and hexagonal crystals). Although this case involved the colon, it seems plausible that
Charcot-Leyden crystal-associated CSH could also occur in the stomach in association with eosinophilic
The patient was treated for her H. pylori infection. Upon repeat EGD 3 months later, a
scar but no nodule was seen in the fundus. The mucosa around the scar was biopsied and was involved by
the B-cell lymphoma and CSH. She then received radiation therapy and an EGD was performed 9 months after
the initial diagnosis; a small nodule and scar were seen in the fundus. The biopsy of the nodule showed
chronic active gastritis and scattered lymphoid aggregates without histiocytes; there was no evidence of
a clonal plasmacytic population. Repeat biopsies 1 year and 21 months after the original diagnosis were
negative for lymphoma and histiocytes.
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