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Papillary Mucinous Adenoma Arising in Adenomyomatous Hyperplasia of the Gall Bladder

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Papillary Mucinous Adenoma Arising in Adenomyomatous Hyperplasia of the Gall Bladder Possible association between Langerhans' cell histiocytosis and germ cell tumour 965 nancies. Report of two cases and review of the literature. Rechavi G. Familial clustering of malignant germ cell Am 7 Surg Pathol 1985;9:23-30. tumors and Langerhans' histiocytosis. Cancer 1994;73: 7 Nichols CR, Hoffman R, Einhom LH, Williams SD, 1980-3. Wheeler LA, Gamick MB. Hematologic malignancies 11 Rabkin MS, Wittwer CT, Kjeldsberg CR, Piepkom MW. associated with primary mediastinal germ cell tumors. Ann Flow-cytometric DNA content of histiocytosis X (Lan- J Clin Pathol: first published as 10.1136/jcp.48.10.965 on 1 October 1995. Downloaded from Intern Med 1985;102:603-9. gerhans cell histiocytosis). Am Jf Pathol 1988;131:283-9. 8 Chaganti RS, Ladanyi M, Samaniego F, Offit K, Reuter 12 Van Heerde P, Maarten Egeler R. The cytology of Lan- VE, Jhanwar SC, et al. Leukemic differentiation of a gerhans cell histiocytosis (histiocytosis X). Cywopathology mediastinal germ cell tumor. Genes Chromosom Cancer 1991;2:149-58. 1989;1:83-7. 13 Gordon S. Defense mechanisms. The mononuclear phago- 9 Nichols CR, Roth BJ, Heerema N, Griep J, Tricot G. cyte system. In: McGee JO'D, Isaacson PG, Wright NA, Hematologic neoplasia associated with primary me- eds. Oxford textbook ofpathology. 1st edn. Oxford: Oxford diastinal germ-cell tumors. N Engl J Med 1990;322: University Press, 1992:236-58. 1425-9. 14 Ladanyi M, Roy I. Mediastinal germ cell tumors and histio- 10 Mandel M, Toren A, Kende G, Neuman Y, Kenet G, cytosis. Hum Pathol 1988;19:586-90. J Clin Pathol 1995;48:965-967 Papillary mucinous adenoma arising in adenomyomatous hyperplasia of the gall bladder G Y Lauwers, S J Wahl, G V Scott, S J DeRoux Abstract Methods A case of papillary mucinous adenoma Sections of the gall bladder were fixed in 10% arising in adenomyomatous hyperplasia buffered formalin and embedded in paraffin (AMH) ofthe gall bladder is reported. The wax. Paraffin wax sections 4 gm thick were lesion was unsuspected and discovered by stained with haematoxylin phloxine saffron. routine palpation ofthe gallbladder during Histochemical stains including periodic acid laparotomy. The adenoma developed Schiff (PAS), with and without diastase pre- within fundal AMH and showed cytological treatment, mucicarmine, and alcian blue were atypia. This case illustrates that neoplastic applied to the sections. Sections were also proliferation is indeed possible in AMH stained immunohistochemically with chromo- and challenges the classical opinion that granin (Boehringer Mannheim, Indianapolis, http://jcp.bmj.com/ AMH is devoid of neoplastic potential. Indiana, USA) monoclonal antibodies using (7 Clin Pathol 1995;48:965-967) the avidin-biotin peroxidase technique, as de- scribed previously.9 Keywords: Gall bladder, cancer, adenomyomatous hyperplasia, adenomyomatosis, mucinous adenoma. Results on September 23, 2021 by guest. Protected copyright. PATHOLOGICAL FINDINGS Adenomyomatous hyperplasia (AMH), also On gross examination, the fundus of the acal- known as adenomyomatosis, is the most fre- culous gall bladder showed a dome shaped, quently diagnosed pseudotumour of the gall 2 x 1-3 x cm. of Florida cystic lesion measuring 1 Micro- University bladder.' Although classically considered to be scopically, the gall bladder mucosa showed College of Medicine, a hyperplastic lesion, recent reports showed Department of normal luminal folds lined by a single layer of Pathology and not only a causative relation between AMH columnar epithelium. The stroma was slightly Laboratory Medicine, and gall bladder carcinoma, but also actual fibrotic and contained lymphocytes in small Gainesville, neoplastic degeneration arising in AMH.2- Florida, USA clusters. AMH was identified within the wall G Y Lauwers Here, we report a unique case of adenomatous of the fundus as the typical multiple ana- G V Scott changes and evidence of neoplastic potential in AMH. stomosing, epithelium lined extrusions ex- Lenox Hill Hospital, tending between bundles of hyperplastic Department of smooth muscle. Foveolar type mucinous meta- Pathology, New York, plasia of the hyperplastic epithelium was also New York, USA Case report present. A large cyst measuring 11 x 5 mm was S J Wahl An 86 year old woman was admitted for surgery observed in continuity with AMH. Its lining S DeRoux J following a diagnosis of adenocarcinoma of the was composed of tall mucinous cells with focal Correspondence to: left colon. A preoperative workup showed no formation of papillae (figs 1 and 2). A large Dr G Y Lauwers, Department of Pathology evidence of metastatic tumour and a left hemi- villous polypoid lesion formed of anastomosing and Laboratory Medicine colectomy was performed. At surgery, pal- fronds protruded into the cystic space. The University of Florida College of Medicine, pation of the gall bladder revealed a small soft fibrovascular stroma of the papillae was in- P.O. Box 100275, mass at the tip of the fundus and a chole- filtrated by lymphocytes and plasma cells. Most Gainesville, Florida 32610, USA. cystectomy was performed. The postoperative of the fronds were lined by a single layer of Accepted for publication course was uneventful and the patient is alive benign mucus cells, although focal cellular tuft- 21 February 1995 and well 17 months after surgery. ing and nuclear atypia were present. 966 Lauwers, Wahl, Scott, DeRoux to the surface epithelium of the gall bladder, the foveolar type metaplastic epithelium of the AMH and the adenoma lacked acid mucins but were positive for neutral mucin. The histo- J Clin Pathol: first published as 10.1136/jcp.48.10.965 on 1 October 1995. Downloaded from logical and histochemical similarity support the conclusion that the papillary mucinous ad- enoma arose from the AMH. To the best of our knowledge, the present case is the first detailed description of such neoplastic change arising within AMH. In 1982, Von Matting et all' described a so-called "benign papillary cystadenoma of the gall bladder fundus", sug- gesting a similar lesion, but their report did not contain a precise microscopic description. AMH, regarded as a hyperplastic lesion, com- bines excessive surface epithelial proliferation with extrusion of the mucosa through a thickened muscular wall." This acquired pro- cess can be diffuse, segmental, or localised with a propensity for the fundus.' Its frequency has Figure 1 Low power view of the fundus of the gall bladder. Prominent AMH extends from the luminal surface (star) into the thickened wall. The AMH associated papillary been reported to vary between 2 and 25% adenoma can also be seen (arrow head). in both surgical and radiological retrospective studies.'213 More commonly recognised in women, its incidence increases with age.'4 Al- though most lesions are asymptomatic, non- specific cholecystitis-like symptoms have been reported.'415 Cyst formation secondary to in- flammation, fibrosis, and inspissated bile has also been described.'4 15 Abscess formation has been the most frequently reported com- plication. 6 The association between AMH and gall blad- V---...... der cancer is unclear.'7 Although regarded clas- ..r4-..- sically as a benign process, recent publications have challenged this opinion. Ootani et a14 redefined the association between AMH and gall bladder cancer. In their series 11-4% of gall bladder cancers developed in the fundal compartment, distal to the stricture induced http://jcp.bmj.com/ by AMH. They suggested that segmental AMH was a causative factor in gall bladder cancer, ... .". k%. %,....,.... but indicated that this relation was not true for l.. M:', diffuse or fundal AMH. Of more interest in the light of the case reported here are the eight cases of gall bladder cancer which developed Figure 2 Lining of the cyst composed of an inconspicuous mucinous epithelium forming directly in AMH.235' The following are of on September 23, 2021 by guest. Protected copyright. small papillary fronds. particular relevance: four ofthe eight gall blad- der cancers developed in localised AMH of the fundus2568; mucinous metaplasia was present HISTOCHEMICAL AND IMMUNOHISTOCHEMICAL in two of these four cases26; and in one case FEATURES the carcinoma arose from a papillary adenoma The surface epithelium of the gall bladder was similar to the case presented in this report.6 positive on staining with alcian blue and neg- The case presented here, supported by the ative with PAS and mucicarmine. In contrast, recent reports of gall bladder cancer arising in the metaplastic foveolar epithelium ofthe AMH AMH, suggests that AMH may have neoplastic and the papillary adenoma was positive on potential. In some cases at least an adenoma staining with PAS, both before and after pre- could be one of the intermediate steps in the treatment with diastase, highlighting neutral carcinogenic sequence. The possibility that mucus cells. Occasional cells were positive on mucinous metaplasia in AMH is indicative of staining with alcian blue and mucicarmine. a predisposition to neoplasia requires in- Immunohistochemical staining with chro- vestigation. That the histological features of mogranin antibodies did not reveal endocrine our case are reminiscent of the mucinous cyst- cells in the metaplastic foveolar epithelium or adenoma of the appendix is of particular in- the adenoma. terest. The clinical significance of our finding is limited at present. AMH is a frequent finding Discussion during surgery and has an excessively low A case of low grade papillary mucinous ad- malignant potential (if any greater than normal enoma arising in AMH, showing foveolar type epithelium). None the less, awareness of the mucinous metaplasia, is reported. In contrast possibility of malignant degeneration might be Papillary mucinous adenoma arising in AMH of the gall bladder 967 enomyomatosis. Am J Gastroenterol 1988;83:670-4. clinically important. As AMH can be easily 7 Nakafuji H, Koike Y, Wakabayashi M, Furihata R, Maru- recognised on ultrasonography,'8 any unusual yama Y, Ogata H. Three cases of early stage carcinoma of the gallbladder. GastroenterolJrpn 1981;16:134-40. modifications of the sonographic structure or 8 Paraf F, Molas G, Potet F.
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