case report malakoplakia of the pancreas with simultaneous...

Case ReportMalakoplakia of the Pancreas with Simultaneous ColonInvolvement: Case Report and Review of the Literature

Surya Guha and Haiyan Liu

Geisinger Medical Center, 100 North Academy Avenue, Danville, PA 17821, USA

Correspondence should be addressed to Surya Guha; surya [email protected]

Received 23 March 2015; Accepted 11 May 2015

Academic Editor: Katsuyuki Aozasa

Copyright © 2015 S. Guha and H. Liu. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Although malakoplakia has been reported to occur at various body sites, pancreatic malakoplakia with simultaneous colonicinvolvement is very rare. Lesions of malakoplakia can masquerade as tumor masses leading to unwanted resections. Nevertheless,malakoplakia can occur in associationwith frank carcinomas, especially in the colon. By reporting a case of pancreaticmalakoplakiadiagnosed by fine needle aspiration cytology, this paper aims to describe cytologic features of malakoplakia and to further reviewfindings from previous reported cases of pancreatic malakoplakia in the literature. With advances in minimally invasive, image-guided aspiration technologies, cytomorphological analyses can diagnose lesions of malakoplakia. This may help avoid surgeriesthat would have otherwise been carried out due to a misleading impression of tumor. However challenges remain as to the furthermanagement of patients diagnosed with this condition. More studies are necessary to determine the probability of malignanciesarising in association with malakoplakia, in order to devise appropriate treatment protocols.

1. Introduction

A seemingly indolent disorder of immune function, malako-plakia, has been known to occur in various body sites,most commonly involving the urinary tract (in at least70% of cases), with isolated reports of involvement of thecolon, stomach, liver, pancreas, skin, and brain. On severaloccasions, malakoplakia presents as a “mass lesion” mislead-ing clinicians toward a suspicion of a tumor. Conversely,malakoplakia has been shown to occur in organs otherwiseharboring a malignancy (usually a carcinoma). In theseinstances, the malakoplakia occurs either as a response to thetumor or as an inciting agent. Other notable associations ofmalakoplakia include immune deficiency disorders, autoim-mune conditions, organ transplantation (as a consequenceof immunosuppression), and metabolic syndromes. Malako-plakias involving the pancreas are rare andmay be diagnosedincidentally during elective cholecystectomy procedures [1].Malakoplakias are infrequently diagnosed by cytologicalstudies [2]. Diagnosis on cytology is further dependent uponthe organ of involvement, which in turn determines the feasi-bility of performing fine needle aspirations. Reports of simul-taneous or sequential organ involvement by malakoplakia

are rare. We report a case of simultaneous involvementof the sigmoid colon and pancreas in a 59-year-old malewith no known risk of immunodeficiency. Diagnosis of thesigmoid colon malakoplakia was performed on a surgicalbiopsy/polypectomy while the pancreatic involvement wasdiagnosed on fine needle aspiration. To our knowledge thisis the first reported case of pancreatic malakoplakia to bediagnosed on cytology.

2. Case Presentation

A 59-year-old gentleman presented to our institution withanemia (hemoglobin: 9.4 g/dL) noted during preoperativeevaluation for a cataract surgery. He was asymptomatic andhad no history of immunodeficiency. His only previoushistory was a cholecystectomy performed 11 years prior tohis current admission. He was noted to have a positivefecal occult blood test prompting colonoscopic evaluationrevealing an 8mm sessile polyp in the sigmoid colon whichwas resected. A second polyp, 3mm in size, was identifiedwithin the ascending colon. No other largemasses ormucosalulcerations were identified. A few weeks later, the patient

Hindawi Publishing CorporationCase Reports in PathologyVolume 2015, Article ID 649136, 5 pageshttp://dx.doi.org/10.1155/2015/649136

2 Case Reports in Pathology

(a) (b)

(c)

Figure 1: (a) Pancreatic fine needle aspirate showing many histiocytes with admixed lymphocytic tangles. Many refractile bodies withconcentric laminations are identified (Diff-Quik, original magnification ×400). (b) Cellblock from pancreatic fine needle aspirate showing agranuloma containing many targetoid Michaelis-Gutmann bodies (arrows) (hematoxylin and eosin, original magnification ×400). (c) Von-Kossa stain highlighting the Michaelis-Gutmann bodies (original magnification ×400).

presented with abdominal pain and nausea, and a ComputedTomography (CT) scan of the abdomenwas performedwhichrevealed a vague mass like area within the pancreas. This wasfollowed up with an endoscopic ultrasound which revealeda 33 × 32mm mass with well-defined borders involving thepancreatic head.No cystic areaswere presentwithin themass.No other abnormalities were detected in the remainder of thepancreas, bile duct, or liver. A fine needle aspiration of thepancreatic mass was performed.

During the next 3-4 weeks, the patient developed gradu-ally worsening abdominal pain, fatigue, and weight loss. Arepeat abdominopelvic imaging study revealed ascites andthe pancreatic mass which had slightly enlarged. Culturesof the ascitic fluid grew Escherichia coli and hence antibi-otic therapy was initiated. Impaired glucose tolerance wasdetected in the ensuing hospital stay. His general condi-tion remained unimproved and he continued to experiencereduction in weight and loss of appetite. Having counseledthe patient on the possibility of a malignancy occurring inassociation with malakoplakias and in the absence of anyother cause for his cachectic symptoms, the patient electedto undergo a pancreaticoduodenal resection (Whipple pro-cedure). The patient reported improvement in his symptomsfollowing surgery. Three months after surgery, he developedrecurrent ascites with no additional imaging abnormalitiesdetected.

3. Pathologic Findings

The fine needle aspirate obtained from the pancreatic headrevealed abundant histiocytes and few admixed lymphocytes.Majority of the histiocytes were present in large sheets. Onthe Diff-Quik stained smears, the histiocytes were found tocontain refractile bodies (Figure 1(a)). Occasional granulo-mas and focal aggregates of neutrophils along with scantnecrotic debris were also present. The background containedfew ductal and acinar cells. Fibrous stromal tissue was alsoidentified. No dysplastic changes or overt features of malig-nancy were present.The cellblock revealedmany granulomascontaining distinctive targetoid bodies (Michaelis-Gutmannbodies) within the histiocytes (Figure 1(b)). A Von-Kossastain performed on the cellblock material revealed dark-brown to black staining of the Michaelis-Gutmann bodies(Figure 1(c)). No organisms were identified by special stains(acid-fast stain, Grocott’s methenamine silver stain). A CD68immunoperoxidase stain highlighted the histiocytes.

The sigmoid colon polyp showed lymphohistiocytic infil-tration of the lamina propria and submucosa (Figure 2(a)).Few scattered Michaelis-Gutmann bodies were identified(Figure 2(b)). Occasional neutrophils and eosinophils werepresent. The colonic mucosal epithelium was unremarkable.The polyp resected from the ascending colon showed atubular adenoma.

Case Reports in Pathology 3

(a) (b)

Figure 2: (a) Sigmoid colon biopsy showing lymphohistiocytic infiltration of lamina propria (hematoxylin and eosin stain, originalmagnification ×200). (b) Higher power view of sigmoid colon biopsy showing Michaelis-Gutmann bodies (arrows) (hematoxylin and eosin,original magnification ×400).

(a) (b)

Figure 3: (a) Section from pancreatic resection showing histiocytes with Michaelis-Gutmann bodies (arrows) (hematoxylin and eosin,original magnification ×400). (b) Focus of pancreatic intraepithelial neoplasia, PanIN-2 (hematoxylin and eosin, original magnification×600).

On gross examination of the Whipple specimen, thepancreatic parenchyma was indurated and mildly congested.Nodiscretemasswas present.Nomucosal abnormalitieswerevisible within the distal stomach, duodenum, or the commonbile duct. On light microscopy, sections from the pancreatichead revealed established chronic pancreatitis with manyareas of lymphocytic inflammation, acinar and ductal atro-phy, and fibrosis. Few scattered plasma cells were present.Additional areas of malakoplakia adjacent to atrophied pan-creatic acini were identified (Figure 3(a)). Interestingly, focallow-intermediate grade pancreatic intraepithelial neoplasia(PanIN-2) was observed (Figure 3(b)). No evidence of highgrade dysplasia or adenocarcinomawas identified in the pan-creas or ampullary region after thorough histopathologicalexamination. The duodenal mucosa and bile duct epitheliawere unremarkable. The surgical resection margins werebenign. Fifteen peripancreatic lymph nodes were examinedand were found to be benign.

4. Discussion

In recognition of the original discoverers of this condition,malakoplakia is ubiquitously characterized by the presence of

targetoid mineralized bodies known as Michaelis-Gutmannbodies. In fact a diagnosis of malakoplakia may be missedin the setting of a paucity of these characteristic bodies[3]. These represent undigested products from phagocytosedbacteria which, owing to their mineralization by calcium andiron, stain positively with the Von-Kossa and Prussian bluestains. Escherichia coli infection has been identified in manycases of malakoplakia involving the urinary tract, althoughother bacteria, viruses, and even protozoa have been impli-cated [4]. Malakoplakias are commonly observed to occurin immunocompromised patients. Why the great majority ofimmune deficient patients do not present with the lesions ofmalakoplakia remains unclear; specific errors in mechanismsinvolving the cyclic guanosine monophosphate pathway thatregulates lysosomal function appear to play a determiningrole. Our patient was noted to have frank diabetes soonafter his diagnosis of pancreatic malakoplakia. It is uncertainwhether the diabetes was the causative factor for, or endresult of, the pancreatic malakoplakia. Occasional reports ofmalakoplakia affecting immunocompetent individuals alsoexist in the literature. Systemic involvement by malakoplakiahas been rarely reported. Our case may be the fourth ina series of case reports detailing systemic involvement by

4 Case Reports in Pathology

Table 1: Summary of features of pancreatic malakoplakia in the literature.

Reference articlenumber

Age (in years) and genderof patient Clinical presentation Additional findings Clinical progression

[1] 75, malePancreatic mass detected

during electivecholecystectomy

No other organ involvement No complications afterexcision of pancreatic mass

[3] 49, male Weight loss and anemia Retroperitonealmalakoplakia

Bone recurrence ofmalakoplakia

[5] 6 weeks, male ImmunodeficiencyAdrenal and colonicinvolvement bymalakoplakia

Expired due to militarytuberculosis

[6] 74, male Fever and abdominal pain,pancreatic tail mass

Peripancreatic lymph nodesinvolved by malakoplakia

Well, 13 months after distalsplenopancreatectomy

[7] 45, female Recurrent abdominal pain

Moderately differentiatedpancreatic ductal

adenocarcinoma withmetastasis

Expired 10 months afterWhipple procedure

malakoplakia. Previous reports include a 49-year-old malewho presented with retroperitoneal malakoplakia and subse-quent bone involvement [3], a 6-week-old male with congen-ital immunodeficiency who presented with appendiceal andcolonic malakoplakia, in addition to pancreatic involvement[5], and a 74-year-old male with pancreatic tail involvementby malakoplakia, along with spread to the peripancreaticlymph nodes [6].

The most common site of involvement of malakoplakiais the urinary tract. Malakoplakias involving the urinarybladder often present as white plaques noted on cystoscopicexamination. The second most frequently involved site is thegastrointestinal tract, particularly the colon. Involvement ofvarious other sites continues to be reported in the literature.As mentioned earlier, cases of malakoplakia involving thepancreas are relatively rare. A PubMed search revealed threepublications reporting malakoplakia involving the pancreas.Zuk et al. [7] describe two additional cases of pancreaticmalakoplakia in their review article. Relevant findings inthese case reports are summarized in Table 1. Two patients [6,7] presented with abdominal pain prompting further evalua-tion, while, in one patient, it was detected incidentally duringelective cholecystectomy [1]. One of the patients describedby Colby [3] was diagnosed with malakoplakia (secondaryto Corynebacterium equi and Klebsiella) which presented asa retroperitoneal mass with additional involvement of thepancreatic tail and mesenteric root of the transverse colon. Ayear after antibiotic therapy he developed recurrent malako-plakia involving the right femur which also grew Corynebac-terium, raising the possibility of immunodeficiency in thepatient. Zuk et al. [7] described a patient with concurrentmalakoplakia andmoderately differentiated adenocarcinomaof the pancreas with widespread metastasis of the tumor andsubsequent demise of the patient. Reports of malakoplakiainvolving lymph nodes have been described [6, 8] and itappears that diffuse lymph node involvement is usuallymore commonly seen in immunocompromised patients.Thesignificance of lymph node involvement by malakoplakia isuncertain at present with some reports describing a poor

prognostic implication [8], while in others [6] the patientshave an uneventful postdiagnosis period.

Malakoplakia is notorious for mimicking a malignantneoplastic process. In fact, in a great majority of cases,the diagnosis first comes to light when a resection hasbeen undertaken for the “malignant neoplasm.” Converselymalakoplakias have been reported to occur in associationwith adenocarcinomas including those of the colon andprostate [9–12]. Malakoplakia can pose significant challengesin staging of tumors as overstaging due to an overestimationof the size of the tumor may occur. Interestingly, malako-plakia is reported to occur at sites of prior radiation treatmentwhich can be falsely Positron Emission Tomography (PET)positive, leading to an impression of tumor metastasis orrecurrence [13].

No specific treatment protocols have been established inthe management of malakoplakia. Although primarily con-sidered a disorder of immune function,malakoplakia by itselfis not particularly debilitating and patients diagnosed withlesions of malakoplakia generally do well. Fluoroquinolones,among other classes of antibiotics, have been utilized in themanagement of malakoplakia, especially in immunocom-promised patients or those with systemic involvement, dueto their ability to achieve therapeutic concentrations withinhistiocytes [14, 15]. Malakoplakia occurring in patients ren-dered immunocompromised by posttransplant immunosup-pressive therapy may experience an improvement in generalwell-being by a trial of reduction in immunosuppression.

Malakoplakias continue to be reported to occur atunusual sites, such as the spleen, nasal cavity, and oropharynx[16–18]. The exact frequency of the association of malako-plakia with malignancy is not known at present and whetherall cases of malakoplakia are to be definitively managed withsurgery due to this risk is open for deliberation. Perhaps thegreatest significance of this condition lies in the fact that itcan be frequently mistaken for malignancy. Hence minimallyinvasive techniques such as fine needle aspiration or biopsieswherever possible may be undertaken to examine the truenature of these mimickers of malignancy.

Case Reports in Pathology 5

Disclosure

Surya Guha is the first author and Haiyan Liu is the coauthor.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper.

References

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[2] M. Perez-Guillermo, J. Sola-Perez, and M. Rodriguez-Bermejo,“Malacoplakia and Rosai-Dorfman disease: two entities of his-tiocytic origin infrequently localized in the female breast—thecytologic aspect in aspirates obtained via fine-needle aspirationcytology,” Diagnostic Cytopathology, vol. 9, no. 6, pp. 698–704,1993.

[3] T. V. Colby, “Malakoplakia. Two unusual cases which presenteddiagnostic problems,” American Journal of Surgical Pathology,vol. 2, no. 4, pp. 377–382, 1978.

[4] M. Jain, V. K. Arora, N. Singh, and A. Bhatia, “Malakoplakiaof the appendix: an unusual association with eggs of Taeniaspecies,”Archives of Pathology andLaboratoryMedicine, vol. 124,no. 12, pp. 1828–1829, 2000.

[5] C. S. Smith, L. B. Kahn, and S. Cywes, “Malakoplakia in child-hood: case report with ultrastructural observations and reviewof literature,” Archives of Pathology & Laboratory Medicine, vol.99, no. 4, pp. 198–203, 1975.

[6] P. G. Nuciforo, L. Moneghini, P. Braidotti, L. Castoldi, P. DeRai, and S. Bosari, “Malakoplakia of the pancreas with diffuselymph-node involvement,” Virchows Archiv, vol. 442, no. 1, pp.82–85, 2003.

[7] R. J. Zuk, J. W. Neal, and S. I. Baithun, “Malakoplakia of thepancreas,” Virchows Archiv A, vol. 417, no. 2, pp. 181–184, 1990.

[8] P. A. Dervan, M. Teeling, J. Dempsey, I. M. Drury, E. O’Malley,and D. O’Connell, “Lymphadenopathy due to fatal histiocyticproliferative disorder containing Michaelis-Gutmann bodies,”Cancer, vol. 57, no. 7, pp. 1337–1340, 1986.

[9] F. Karasavvidou, S. P. Potamianos, S. Barbanis et al., “Malako-plakia of the colon associated with colonic adenocarcinomadiagnosed in colonic biopsies,” World Journal of Gastroenterol-ogy, vol. 13, no. 45, pp. 6109–6111, 2007.

[10] B. Asiyanbola, P. Camuto, and V. Mansourian, “Malakoplakiaoccurring in association with colon carcinoma,” Journal ofGastrointestinal Surgery, vol. 10, no. 5, pp. 657–661, 2006.

[11] D. L. Repassy, A. Ivanyi, S. Csata, and G. Tamas, “Combinedoccurrence of prostate carcinoma andmalacoplakia,” Pathology& Oncology Research, vol. 8, no. 3, pp. 202–203, 2002.

[12] K. Pillay and R. Chetty, “Malakoplakia in association withcolorectal carcinoma: a series of four cases,” Pathology, vol. 34,no. 4, pp. 332–335, 2002.

[13] R. L. Kradin, T. A. Sheldon, P. Nielsen et al., “Malacoplakia ofthe tongue complicating the site of irradiation for squamous cellcarcinoma with review of the literature,” Annals of DiagnosticPathology, vol. 16, no. 3, pp. 214–218, 2012.

[14] G. R. Dohle, J. Zwartendijk, and J. H. J. M. van Krieken, “Uro-genital malacoplakia treated with fluoroquinolones,” Journal ofUrology, vol. 150, no. 5, part 1, pp. 1518–1520, 1993.

[15] R. van Furth, J. W. van’t Wout, P. A. Wertheimer, and J.Zwartendijk, “Ciprofloxacin for treatment ofmalakoplakia,”TheLancet, vol. 339, no. 8786, pp. 148–149, 1992.

[16] A. A. Mannan, M. C. Sharma, and S. Bahadur, “Malacoplakiaof the vallecula masquerading as a malignancy,” Ear, Nose, &Throat Journal, vol. 90, no. 3, pp. E17–E19, 2011.

[17] G. Akkuzu, E. Aydin, B. Bilezikci, B. Akkuzu, and L. N.Ozluoglu, “Malakoplakia in nasal vestibule,” Otolaryngology—Head and Neck Surgery, vol. 135, no. 4, pp. 636–637, 2006.

[18] W. O. Greaves and L. J. Wang, “Malakoplakia of the spleen: acase report,” International Journal of Surgical Pathology, vol. 18,no. 6, pp. 584–587, 2010.

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