Pancreatic mucinous cystadenocarcinoma with pseudosarcomatous mural nodules. A report of a case with immunohistochemical study

Pancreatic Mucinous Cystadenocarcinoma With Pseudosarcomatous Mural Nodules A Report of a Case With lrnrnunohistochernical Study Juan Antonio Garcia Rego, MD,* Luis Valbuena Ruvira, MD,t August0 Alvarez Garcia, MDJ Ma Paz Santiago Freijanes, MD,§ Jose Manuel Suarez Peiiaranda, MD,§ and Jose Manuel Rois Soto, MDS A case of pancreatic mucinous cystadenocarcinoma (PMC) with two pseudosarcomatous mural nodules (PMN) is described. These nodules have not been previously described in this type of tumor. In ovarian mucinous tumors (OMT), similar nodules have been reported, the nature of which has been discussed in detail. Here the similarity between the tumor described here and ovarian tumors is stressed. The immunohistochemical study carried out disclosed in the nodules strong positive staining for vimentin and moderate positivity for keratin and epithelial membrane antigen. These findings, along with histologic details, favor the epithelial nature of the nodules. It was concluded that the nodules are foci of anaplastic carcinoma with high proliferative cell rate, which could explain the coexpression of vimentin and keratin. Cancer 67:494-498,1991.

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cystadenocarcinoma (PMC) is very uncommon, representing only from 1% to 2% of all malignancies in this organ.’ We will present a case of PMC with pseudosarcomatous mural nodules (PMN), a finding which, to the best of our knowledge, was not previously published in this location. Mural nodules of similar histologic appearance have been reported in ovarian mucinous tumors (OMT), and their nature and significance in the prognosis is still in dispute.*-’ In our case, the histologic picture and the immunohistochemical findings favored the interpretation that the sarcoma-like nodules represented areas of poorly differenciated carcinoma. HE PANCREATIC MUCINOUS

Case Report A 45-year-old woman underwent surgery in another hospital 2 years before admission to our hospital due to a pseudopancreatic cyst, the exact nature of which could not be confirmed.

At the prior admission the cyst was drained in the stomach by means of an internal anastomosis (cystogastrostomy). After 1.5 years, during which the patient did well, she began to have pain in her left hypochondrium. After 6 months, during which she experienced episodes of intermitent pain, she came to the hospital. A physical examination showed, on palpation, a slightly painful round mass in her left hypochondrium. The abdominal computerized axial tomographic study showed a well-encapsulated cystic tumor in the pancreatic area. Laboratory data showed a leucocytosis of 9 170/ml. All other values were normal. The patient underwent a laparotomy, and a round tumor located in the body tail of the pancreas was found. A partial pancreatectomy with splenectomy was carried out, and closure of the previous anastomosis (cystogastrostomy) was performed. A small fragment of colon adhering to the tumor was also resected. At 16 months postdiagnosis, she remained disease-free clinically and radiographically.

Materials and Methods

Tissue for light microscopic study was fixed in 10% buffered formalin, embedded in paraffin, and stained with hematoxilin and eosin (H & E), periodic acid-Schiff (PAS), diastase-PAS, alcian blue, Masson’s trichome, Wilder’s reticulin, and the Fontana-Masson’s technique. In addition, sections of paraffin-embedded tissue were prepared for immunohistochemical studies using the peroxidase-antiperoxidase technique (PAP) for the polyclonal antibodies against keratin (KER), carcinoembryonic antigen (CEA), desmin (DES), S-100 protein (Sloo), somatostatin (SOM), gastrin (GAS), glucagon

From the Department of Pathology. Hospital of the Sotial Security “Juan Canalejo,” La Coruiia. Spain. * Department of Pathology. Hospital “Arquitecto Marcide,” Ferrol, La Coruiia. Spain. t Department of Pathology. Hospital “Juan Canalejo,” La Corufia, Spain. $ Department of Pathology. Hospital “Juan Canalejo,” La Corufia, Spain. 5 Department of Pathology, Hospital “Juan Canalejo,” La Coruiia, Spain. Address for reprints: Luis Valbuena Ruvira, MD, Hospital “Juan Canalejo,” Jubias de Arnba 84, I5006 La Corufia, Spain. Accepted for publication March 15, 1990.

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FIG. 1. Multilocular mucinous cystadenocarcinoma of the pancreas showing one mural solid nodule (asterisk) near the splenic hilium.

(GLU), and neuron-specific enolase (NSE) (DAKO, Dakopatts, Glostrup, Denmark). The avidin-biotin-peroxidase technique was employed for the monoclonal antibodies against epithelial membrane antigen (EMA) and vimentin (VIM) (DAKO, Dakopatts). The positive reaction was evaluated as slight (+), moderate (++), and intense (+++).

Results

adhered to the splenic hilium. Sectioning disclosed numerous cysts filled with mucinous or hemorragic material. The inner surface of some cysts was smooth, whereas others had small papillary projections. In the tumor capsule, close to the splenic hilium, there were two independent solid nodules of firm consistency, with poorly defined margins. The bigger nodule measured 2’5 X 2 cms, and the other nodule measured 2 X 1’5 cm (Figs. 1 and 2).

Gross Examination

Light Microscopic Study

The surgical specimen included a round tumor of 1 1 cm in greatest diameter, well encapsulated and closely

The cysts were covered with mucinous epithelium of intestinal type with numerous goblet cells and scattered

FIG.2. Low power photograph showing one mural nodule (asterisk) near the cystic tumor (arrows).

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FIGS.3A AND 3B. (A) The small arrows indicate areas of mucinous cystadenoma. Inset: Benign-looking mucinous epithelium at higher magnification. The big arrow indicates cyst lined by several layers of mucinous atypical epithelium (H & E, XIOO). (B) Invasive mucinous carcinoma (H & E, X100).

cells with faintly granular eosinophilic cytoplasm staining positive with the Masson-Fontana’s stain. A great variation was observed in the cytologic as well as in the architectural pattern of the epithelium among the cysts and even within the same cyst. There were benign areas, cytologically malignant in situ areas, and clearly invasive adenocarcinoma (Fig. 3). Outside the capsula, compressed pancreatic tissue and lymphoid aggregates were found. The capsular nodules were comprised of fusiform cells arranged in fascicles and sheets reminiscent of leiomyo-

sarcoma. There were scattered malignant glands surrounded by atypical cells with pleomorphic nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm with well-defined borders (Fig. 4).

I mmunohistochemist ry The immunohistochemical findings are summarized in Table 1. In the cystic areas the epithelium showed intense cytoplasmic positivity for EMA, CEA, and KER. The scattered argentaffin cells showed intense positivity for

FIGS.4A AND 4B. (A) Glandular elements (arrows) in transition t o undifferentiated and spindle cells (H & E, X200). (B) Sarcomatoid area (H & E, X200).

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SOM and NSE. The PMN showed intense-to-moderate positivity for VIM and moderate positivity for EMA and KER (Fig. 5).

Discussion The presence of PMN in OMT was first reported by Prat and S c ~ l l in y ~1979. ~ ~ Subsequent to the publication of these articles several cases have been p ~ b l i s h e d . The ~-~ nature of these mural nodules has been characterized in different ways by different the authors. The different histogenetic possibilities could be summarized as follows: Reactive sarcoma-like nodules that do not worsen the prognosis of the mucinous tumor,3 "bona fide" sarcomatous nodules usually formed by spindle and anaplastic carcinoma formed by oval-tospindle cell^.^,^ The latter two forms overshadow the prognosis of the tumor in which they are found. Another case was reported with a mixture of sarcoma-like nodule and anaplastic carcinoma.6 Our case bears total likeness to the OMT mentioned, and the presence of PMN reinforces this parallelism. Although in this case the PMN showed wide fields of fusocellular sarcomatous appearance, in the same areas there was transition from spindle cells to neoplastic glandular elements. This fact, along with the reticulin pattern showing fibers encircling groups of cells, supports the interpretation that these nodules are of epithelial nature and represent foci of anaplastic carcinoma. The immunohistochemical study showed positivity for VIM in the nodules, an intermediate filament traditionally associated with mesenchymal cells. This fact has been interpreted by some authors as proof of the sarcomatous nature of the mural nodule^.^ In addition to the positivity for VIM and there was, in the same areas, moderate positivity for KER and EMA.

TABLE1. Immunohistochemical Findings

KER EMA CEA VIM DES SOM GAS

GLU

s-100 NSE

Cvstic areas

Mural nodules

+++ +++ +++

++ ++

0 0

++i

+++* 0 0 0

+++*

+++: positive reaction, intense; reaction. * Positivity in argentaffin cells.

0 0 0 0 0 0 0

++: moderate; +: slight: 0: negative

FIGS,5A A N D 5B. (A) Immunostaining for keratin demonstrating strong positivity in glandular elements and in some undifferentiated and fusocellular cells (original magnification, X300). (B) lmmunostaining for Vimentin, negative in glandular areas (arrow and asterisk) and strongly positive in sarcomatoid areas (original magnification, X300).

The coexpression of KER and VIM in the same group of cells was considered unusual,s~'O but more recently it has been demonstrated in several epithelial tumors and cell cultures.' '-15 The additional expression of VIM has been related to the proliferative cell rate. In cultures of keratinocytes and mesothelial cells, therefore, the inmature proliferating cells show strong expression for VIM, whereas the expression of KER is decreased or absent. In the differentiated cells, the immunohistochemical profile is the opposite.11,'3 Another possible explanation for this coexpression was linked by some authors to certain levels or directions of cell differentiation. In our case, we consider the PMN to be areas of anaplastic carcinoma with a high proliferative rate, which could explain the coexpression of KER and VIM, as well as the stronger positivity of the latter.

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REFERENCES I . Reyes M, Rufian S, Varo E el a/. Neoplasias Quisticas malignas del pancreas. Rev ESP EnfAp Digest 1986; 70:552-556. 2. Prat J, Scully RE. Sarcomas in ovarian mucinous tumors: A report of two cases. Cancer 1979; 44: 1327-1 33 1. 3. Prat J, Scully RE. Ovarian mucinous tumors with sarcoma-like mural nodules: A report of seven cases. Cancer 1979: 44: 1332-1 344. 4. Prat J, Young RH, Scully RE. Ovarian mucinous tumors with foci of anaplastic carcinoma. Cancer 1982; 50:300-304. 5. Czernobilsky B, Dgani R, Roth LM. Ovarian mucinous cystadenocarcinoma with mural nodule of carcinomatous derivation. Cancer 1983; 51:141-148. 6. Fuji S, Konishi I, Kobayashi F, Okamura H, Yamabe H, Mori T. Sarcoma-like mural nodules combined with a microfocus of anaplastic carcinoma in mucinous ovarian tumor. Gynecol Oncol 1985; 20:2 19233. 7. Bruijn JA, Smit VTh, Que D-G, Fleuren GJ. Immunohistology of a sarcomatous mural nodule in an ovarian mucinous cystadenocarcinoma Int J Gynecol Path01 1987; 6:287-293. 8. Damjanov I. Antibodies to intermediate filaments and histogencsis (Editorial). Lab Invest 1983; 47:215-2 17.

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9. Nagle RB, McDaniel KM, Clark VA, Payne CM. The use of antikeratin antibodies in the diagnosis of human neoplasms. Am d Clin Path01 1983; 791458-466, 10. Osborn M, Weber K. Biology of disease. Tumor diagnosis by intermediate filament typing: A novel tool for surgical pathology. Lab lnvesl 1983; 48:372-394. 1 1. Van Muijen GNP, Ruiter DJ, Warnaar SO. Coexpression of intermediate filament polypeptides in human fetal and adult tissues. Lab Invest 1987; 57:359-369. 12. Erlandson RA. Diagnostic immunohistochemistry of human tumors: An interin evaluation. A117 J Surg Pathol 1984: 8:615-623. 13. Connell ND, Rheinwad JG. Regulation of the cytoskeleton in mesothelial cells: Reversible loss of keratin and increase in vimentin during rapid growth in culture. Cell 1983; 34:245-253. 14. Gown AM, Vogel AM. Monoclonal antibodies to human intermediate filament proteins: Ill Analysis of tumors. Am J Clin Pathol 1985; 84:413-424. 15. Sato M, Hayashi Y, Yanagawa T ei a/. Intermediate-size filaments and specific markers in a human salivary gland adenocarcinoma cell line and its nude mouse tumors. Cancer Res 1985; 45:3878-90.