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Journal of Veterinary Diagnostic

http://vdi.sagepub.com/content/21/5/715Theonline version of this article can be found at:

DOI: 10.1177/104063870902100521

2009 21: 715J VET Diagn InvestCastagnaro

Gabrita De Zan, Valentina Zappulli, Laura Cavicchioli, Linda Di Martino, Eriberta Ros, Giorgia Conforto and MassiGastric B-Cell Lymphoma with Mott Cell Differentiation in a Dog

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J Vet Diagn Invest 21:715719 (2009)

Gastric B-cell lymphoma with Mott cell differentiation in a dog

Gabrita De Zan,1 Valentina Zappulli, Laura Cavicchioli, Linda Di Martino, Eriberta Ros,Giorgia Conforto, Massimo Castagnaro

Abstract. A gastric lymphoid tumor with involvement of regional lymph nodes and spleen was diagnosedin an 8-year-old crossbreed male dog with a 6-month history of gastrointestinal disease. Despite surgicalexcision and palliative therapy (prednisolone and cimetidine), the dog was euthanized due to worsening ofclinical signs. At necropsy, multiple white, solid, nodular, infiltrative masses were observed in the stomach,duodenum, spleen, liver, and lungs in association with generalized lymph node enlargement. Cytology,histology, histochemistry, immunohistochemistry, and electron microscopy revealed that the neoplastic cellpopulation was composed of B lymphocytes that contained variable amounts of round periodic acidSchiff-

positive cytoplasmic globules consistent with Russell bodies. The tumor most likely represented a variant of B-cell neoplasia with extensive Mott cell differentiation.

Key words: B-cell lymphoma; dogs; electron microscopy; immunohistochemistry; Mott cell.


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Multiple ultrasound-guided fine-needle aspirations wereobtained from the masses and routinely stained with May-Grunwald/Giemsa.

The gastric mass and the suspected enlarged perigastriclymph node were surgically excised and submitted forhistology. Palliative therapy with prednisolone (1 mg/kg/twice a day) and cimetidine (5 mg/kg/3 times a day) wasadministered. Abdominal ultrasonography was repeatedafter 2 months and revealed a focal perigastric hyperecho-genic area, possibly consisting of a second enlarged

perigastric lymph node, and a 1-cm diameter, splenicnodule. Ultrasound-guided fine-needle aspirates werecollected from both lesions.

After 7 months of clinical recovery, gastrointestinalclinical signs recurred and the owner requested euthanasia.Postmortem examination revealed approximately 200 ml ofserous thoracic effusion and multiple white, solid, round,

0.25-cm diameter, infiltrative masses involving the gastricwall, duodenum, spleen, liver, and lungs. The right axillary,sternal, para-aortic, hepatic, gastric, and mesenteric lymphnodes were enlarged with fatty cut surfaces and obscuredcortico-medullary junctions.

Selected tissues samples obtained at surgery biopsy andnecropsy were fixed in 10% neutral buffered formalin,

embedded in paraffin, sectioned at 3-mm, and routinelystained with hematoxylin and eosin. Replicate tissuesections also were stained by the periodic acidSchiffreaction and with Giemsa stain for the gastric samples.Immunohistochemistry was performed on replicate sectionsof stomach, lymph nodes, spleen, and lung. The primaryantibodies recognized the following antigens: cluster ofdifferentiation (CD)3,a CD5,a CD20,c CD45,c CD45RA,c

CD79acy,a myeloid/histiocytic antigen,a B-lymphocyte an-tigen 36b; immunoglobulin A (IgA),c IgG,c and IgM.c Aportion of formalin-fixed, paraffin-embedded, perigastric

lymph node was submitted for transmission electronmicroscopy (kindly performed by Prof. M. L. Valente,School of Medical and Surgical Sciences, Padova, Italy).

Despite preservation artifacts, cytologic specimens re-vealed a heterogeneous cellular population of 1020-mm

diameter round cells with indistinct borders and moderateto abundant amounts of cytoplasm. The cytoplasm wasdensely packed with numerous well-demarcated 0.31-mm

diameter clear globules that were morphologically consis-

tent with Russell bodies and often obscured nuclear detail.Individual nuclei measured 715 mm in diameter and were

irregularly round with a fine chromatin pattern. Numerouscells showed an immature lymphoid or plasmacytoid

differentiation together with variable numbers of intracy-

toplasmic clear vacuoles or globules consistent with Russellbodies. Mitotic figures were rare, and numerous dissemi-nated clear globules (Russell bodies) were present in the

background. Immature lymphocytes and plasma cells wererare. Numerous free nuclei were also present (Fig. 1).

Histologic examination of gastric wall, duodenum,spleen, liver, lungs, kidney, and lymph nodes tissue revealed

a dense, infiltrative, round cell population that wasdiffusely distributed or separated into nodular aggregates

by minimal to thick fibrovascular stroma. The architecture

of the lymph nodes was severely and diffusely effaced. Inthe stomach, there was a transmural distribution with

occasional mucosal erosions. In the duodenum, focallyextensive nodular infiltrates were observed within the

muscular layers. Neoplastic cells were arrayed in multifocalto coalescing, irregularly round nodules that invaded the

parenchyma of the spleen, lung, and liver. In the kidney,multifocal infiltrates of neoplastic cells were observedbeneath the capusule and within the interstitium.

Histologically, the neoplastic cells were morphologically

similar to those seen in cytologic preparations (Fig. 2).These were mainly round cells, ranging in size from 7 to

15 mm in diameter with occasional cells reaching 50 mm indiameter. They also had variable amounts of cytoplasm

filled with intensely eosinophilic, periodic acidSchiff-

Figure 1. A heterogeneous cell population is composed

mainly of atypical lymphoid cells containing variable numbers ofclear globules consistent with Russell bodies (arrow), which are

also distributed in the background of the preparation. There are

scattered immature lymphocytes (arrowhead) and rare plasmacells. Numerous free nuclei are also present. Fine-needle aspirate;B-cell lymphoma with Mott cell differentiation; gastric wall; dog.May-Grunwald/Giemsa stain. Bar 5 40 mm.

Figure 2. A dense infiltration of irregularly round lymphoid

cells with variable numbers of round cytoplasmic globules(arrows) are present. Histologic section; B-cell lymphoma with

Mott cell differentiation; gastric wall; dog. Hematoxylin andeosin. Bar 5 10 mm.

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positive, 110-mm diameter Russell bodies that frequentlyobscured the nucleus. Nuclei were irregularly round,57-mm diameter, rarely indented, and vesicular or withclumped chromatin and contained multiple eosinophilicnucleoli. Mitotic figures were rare (02 per 403 field ofview). Intermixed with this population were occasionalimmature lymphoid or plasmacytoid cells. The former were

characterized by a high nuclear-to-cytoplasmic ratio, scantbasophilic cytoplasm, and round or indented nucleus thatwas 714 mm in diameter with a fine chromatin pattern.Plasmacytoid cells contained scant, homogenous, basophil-ic cytoplasm that at times exhibited a clear perinuclearhalo. Individual nuclei were centrally located, round, andapproximately 10 mm in diameter and contained hyper-chromatic, clumped chromatin. Both the lymphoid andplasmacytoid cells contained variable numbers of Russellbodies. Similar to the cytologic findings, rare immaturelymphocytes and plasma cells also were observed. Multi-focal necrosis and occasional vascular invasion were noted.Giemsa staining for the detection of Helicobacter spp.organisms in the gastric samples was negative.

After immunohistochemical staining, the neoplasticlymphocytes had diffuse, specific but variable, cytoplasmicreactivity with anti-CD79acy, antiB-lymphocyte antigen36, anti-CD45, anti-CD45RA, and anti-CD20 antibodies.Scattered lymphocytes and lymphoid aggregates that wereintermingled with the neoplastic cell population hadmoderate cytoplasmic staining with anti-CD3 antibodiesand intense cytoplasmic staining with anti-CD5 antibodies.Scattered histiocytic cells stained with the anti-myeloid/histiocyte antigen antibody. Anti-IgM, anti-IgA, and anti-IgG antibodies produced inconsistent, weak cytoplasmicstaining and, therefore, were considered negative.

Despite some cellular disruption due to formalin-fixationand paraffin embedding, ultrastructural examination of 1

perigastric lymph node allowed the identification ofvariable numbers of osmiophilic, cytoplasmic structureswithin ectatic cisternae of the rough endoplasmic reticulum.These cells were identified as Mott cells (Fig. 3). Rareplasma cells and immature lymphocytes were also ob-served.

Based on the cytologic, histologic, immunohistochemi-cal, and ultrastructural findings, the present case wasdiagnosed as a lymphoid neoplasm with diffuse Mott celldifferentiation. This tumor most likely originated from thegastric wall and resulted in multiple visceral and lymphnode metastases. Specific cytoplasmic staining forCD79acy, B-lymphocyte antigen 36, CD45, CD45RA,and CD20 polypeptides indicated that the neoplastic

lymphocytes were of B-cell origin.A similar lymphoid neoplasm has been infrequently

described in humans and diagnosed by some authors as aMott cell tumor.3,13 Only 2 cases have been diagnosedrecently: 1 neoplasm originated in the stomach in associ-ation with Helicobacter pylori infection,3 and 1 neoplasmoriginated in the rectum.13 An additional gastric Mott cellneoplasm also has been reported by Russian investigators.7

In human medicine, an unusual gastric lesion calledRussell body gastritis occurs in association with H. pyloriinfection. This form of gastritis is characterized by localized

accumulations of Mott cells and plasma cells. Despite itsmonomorphic, plasmacytic appearance, this lesion is notconsidered neoplastic because of its polyclonal immuno-reactivity.8 In the neoplasm of the present report, thepossibility of a similar inflammatory lesion was considered

but excluded based on the presence of metastases, themorphologic appearance, and the absence of Helicobacterspp. microorganisms in gastric samples. In 2008 and 2009,analogous cases of Mott cell tumors were reported indogs,6,12 and all were characterized by primary involvementof the gastrointestinal tract, as in the present report.

However, the tumors in the analogous cases were lessadvanced than those of the present case.

The atypical lymphoid population described in humancases was mixed and consisted of centrocyte-like cells,plasmacytic cells, and Mott cells. In addition, these lesionswere associated with peripheral secondary or scatteredatrophic lymphoid follicles, leading the authors to postulatea possible origin from the mucosa-associated lymphoid

tissue. Thus, mucosa-associated lymphoid tissue lymphomawith marked Mott cell differentiation was suggested as themost likely diagnosis.3,13 Based on plasmacytic differen-tiation of mucosa-associated lymphoid tissue lymphomas,a differential diagnosis of extramedullary plasmacytomahas also been suggested.4

In the present canine neoplasm, there was no evidence ofresidual mucosa-associated lymphoid tissue, and an originfrom this lymphoid follicular tissue appeared less likely. Inaddition, the typical morphology of an extramedullaryplasmacytoma was not observed9,15 in cytologic samples or

Figure 3. Electron micrograph with 5 irregularly round cellsthat contain variable amounts of cytoplasmic osmiophilic materialwithin ectatic cisternae of the rough endoplasmic reticulum

(arrows) consistent with Russell bodies. These cells were identifiedas Mott cells. Electron micrograph; B-cell lymphoma with Mott

cell differentiation; perigastric lymph node; dog. Bar 5 2 mm.

Case Reports 717



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in histologic sections, excluding the diagnosis of a classicalextramedullary plasmacytoma. Moreover, the CD20-posi-tive staining of the neoplastic cells of the current casesuggested a B-cell lineage without differentiation to matureplasma cells. Cluster of differentiation 20 is usuallyexpressed in B-cell precursors and in mature B lymphocytesbut is normally lost during differentiation towards plasma

cells. A 2007 report found CD20 to be the least likelyrepresentative marker in canine plasmacytomas.10 No dataare available regarding CD20 expression in the few cases ofMott cell tumors reported in humans.3,7,13 Cluster ofdifferentiation 20 detection was described only in the firstveterinary report.6 In the same report, immunohistochem-ical staining for Pax-5 confirmed that the cellular popula-tion was lymphoid, leading to speculation of a directtransformation into Mott cells.6 The same conclusion,based on the absence of morphologic and ultrastructuralaspects of plasma cell differentiation, was also reported inthe second veterinary publication.12 In contrast, the 2cellular populations in the present case had either immaturelymphoid or plasmacytoid features in association with

variable amounts of Russell bodies, suggesting differentdevelopmental stages toward Mott cells in both cellularpopulations.

The diffuse, intense period acidSchiff staining of thecytoplasmic globules and the ultrastructural localizationwithin ectatic cisternae of the rough endoplasmic reticulumwere compatible with Russell body formation. Russellbodies are composed of condensed immunoglobulinswithin dilated cisternae of the rough endoplasmic reticulum

in B-cell populations. They are associated with a highproliferative rate of mature B cells and aberrant formationof mutant and nonsecretable immunoglobulin molecules.14

Russell bodylike structures or intracisternal granules havealso been identified in secretory cells that are unable to fully

degrade certain insoluble molecules (i.e., zymogen granulesof the exocrine pancreas).14 Segregation of these aggregateswithin the cisternae of the endoplasmic reticulum promotescellular survival by maintaining the secretory pathway andthe cellular traffic.14

The neoplasm of the present report had an unexpectedlack of immunohistochemical staining for immunoglobu-lins. Usually, extramedullary plasmacytomas in dogs stainpositively for immunoglobulins, especially monoclonallight-chain reactivity.9 In humans, sporadic Mott celltumors revealed a diffuse, monotypic IgG kappa chainprofile.3,13 Both previous veterinary reports of similarneoplasms had positive staining results for immunoglobulins.The first report described an IgM lambda chain profile of the

Mott cells. In the second report, reactivity for IgM waspresent in the Mott cells of dog 1 while reactivity to both IgGand IgM was observed in the Mott cells of dog 2.6,12

Although immunoglobulin reactivity is a standard andsensitive test for plasma cell identification, some conditionsmay prevent immunoglobulin detection. Some evidence oflow specificity of immunoglobulin detection has beenattributed to nonspecific surface immunoglobulin adsorp-tion, internalization of Ig-opsonins complexes within macro-phages, and binding of immunoglobulins to a variety of celltypes via Fc receptors.11 Too few cases of lymphoid neoplasia

with Mott cell differentiation have been investigated to make

definitive conclusions regarding the validity of immunohis-tochemical detection of immunoglobulins. In the presentneoplasm, the possibility of low specificity in immunoglob-

ulin detection cannot be completely excluded.

To further classify this unusual neoplasm, the presence

or absence of a monoclonal gammopathy should have been

assessed, as well as the clonality of the tumor cellpopulation. Unfortunately, these analyses were not per-formed because serum and urine were not submitted by the

clinician for protein electrophoresis and frozen tissue wasnot collected for molecular analysis.

Acknowledgements. The authors thank Prof. P. F.

Moore and Dr. V. K. Affolter for performing theimmunohistochemical staining and Prof. Maria Luisa

Valente and Dr. Mila Della Barbera for performingtransmission electron microscopy.

Sources and manufacturers

a. Dako North America Inc., Carpinteria, CA.

b. Novocastra Laboratories Ltd., Newcastle upon Tyne, UK.

c. Prof. P. F. Moore, University of CaliforniaDavis, Davis, CA.

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lymphoreticular system (including thymus). In: Diagnostic

histopathology of tumors, ed. Fletcher CDM, vol. II, pp. 805

927. Churchill Livingstone, New York, NY.

2. Coyle KA, Steinberg H: 2004, Characterization of lympho-

cytes in canine gastrointestinal lymphoma. Vet Pathol

41:141146.

3. Fujiyoshi Y, Inagaki H, Tateyama H, et al.: 2001, Mott cell

tumor of the stomach with Helicobacter pylori infection.

Pathol Int 51:4346.4. Hussong JW, Perkins SL, Schnitzer B, et al.: 1999, Extra-

medullary plasmacytoma: a form of marginal zone cell

lymphoma? Am J Clin Pathol 111:111116.

5. Jacobs RM, Messick LB, Valli VE: 2002, Tumors of

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11. Schrenzel MD, Naydan DK, Moore PF: 1998, Leukocyte

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dogs. Vet Clin Pathol 38:113120.

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lymphoma with extreme plasma cell differentiation of the

rectum. Am J Gastroenterol 97:18601862.

14. Valetti C, Grossi CE, Milstein C, Sitia R: 1991, Russellbodies: a general response of secretory cells to synthesis of amutant immunoglobulin which can neither exit from, nor be

degraded in, the endoplasmic reticulum. J Cell Biol115:983994.

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