Pseudomyxoma peritonei

A 46-year-old woman with no significant medical history presented with pelvic pain and abdominal enlargement during the last 6 months. Physical examination revealed a mass in the left side of the pelvic region. Ultrasound examination disclosed a large heterogeneous multicystic mass in the left ovary, measuring 21 cm in its maximum diameter. There was neither ascites nor other abnormalities in the pelvic cavity.

A left-sided oophorectomy was performed and a specimen submitted for pathologic examination. During the surgery, no other abnormalities were observed. The gross specimen consisted of a 21 x 19 x 14-cm multicystic mass, with a gray smooth external surface. The sectioned surface showed a thin-walled multilocular mass filled with whitish viscous fluid. In a focal area that measured 3.5 X 3.0 cm, the walls of the loculi were thicker and presented 3 discrete, yellowish, poorly defined nodules, ranging from 4 to 10 mm in their maximum diameter. Histologically, the tumor was composed of glands and thinwalled cysts lined by a mixture of endocervical-type and intestinal-type mucinous epithelium with goblet cells (Figure 1, A). In some areas, there were filiform and complex papillae and cribriform and back-to-back glandular formations lined by columnar cells and goblet cells with enlarged nuclei and occasional distinct nucleoli. In these areas, normal and abnormal mitotic figures could be observed (Figure 1, B). In all of these aspects, the tumor stroma resembled the ovarian stroma, with scattered foci of acute and chronic inflammation.

Samples from the yellowish and poorly defined nodules observed during gross examination showed a peculiar histologic appearance. Ill-defined nodules composed of sheets and nests of anaplastic large epithelioid cells, with voluminous vesicular nuclei containing 1 to 3 distinct macronucleoli, and well-defined eosinophilic to amphophilic cytoplasm (Figure 2, A and B) infiltrated the stroma of these areas. Scattered spindle-shaped atypical cells and lymphocytes were seen. After extensive sampling, no transition or continuity between these nodules and the mucinous epithelium could be found. The anaplastic cells were positive for cytokeratin (Figure 2, C) and epithelial membrane antigen (Figure 2, D). Vimentin-positive epithelioid and spindle-shaped cells were barely observed. Occasional mitoses (Figure 2, C and D, arrowheads) and abortive gland formations (Figure 2, D, arrow) were seen. Other immunohistochemical markers, including S100 protein, desmin, actin, and CD34, were all negative.

What is your diagnosis?

Pathologic Diagnosis: Mucinous Cystic Tumor of Borderline Malignancy, Intestinal Type, With Mural Nodules of Anaplastic Carcinoma

Mural nodules are unusual findings of otherwise typical mucinous cystic tumors of the ovary.1-3 They are defined as nodules of variable histologic appearances arising in the walls of mucinous tumors (MTs) and differing from the MTs themselves.1-3 These nodules have been described in MTs of several organs, including the pancreas 4 bladder, and ovary. Mural nodules arising in ovarian MTs were first characterized by Prat and Scully5 in 1979, who described 7 cases of sarcoma-like nodules (SLNs) arising in the walls of ovarian MTs.5 Since this first description, several studies that described these unusual findings and attempted to develop a comprehensive histogenetic classification have been performed.1-3 The current concept is that these nodules should be classified according to their histologic and immunohistochemical features in (1) anaplastic carcinoma (AC), (2) sarcomas, (3) carcinosarcomas, (4) SLNs, (5) mixed nodules (MNs), and (6) leiomyomas.3

Mural nodules of AC are rarely found in the walls of cystic MTs,1-3 and to the best of our knowledge no more than 16 cases have been reported so far.1-3,6-10 The gross appearance of these nodules is highly variable; they may be single or multiple, ranging from less than 1 cm to more than 11 cm in diameter.1-3,6,10 On histologic examination, nodules of AC are poorly circumscribed and infiltrative. They are composed of either epithelioid or spindle-shaped cells, with voluminous cytoplasm and large and pleomorphic nuclei with distinct nucleoli.1-3,6--10 A variable number of typical and atypical mitotic figures, as well as a minor component of inflammatory cells, might be seen in almost every case.1-3,6-10 Abortive gland formations and foci of vascular invasion are occasionally found.1-3 Immunohistochemical analysis usually supports the epithelial origin of the atypical cells, with positive immunoreactivity for epithelial membrane antigen (EMA) and cytokeratin.1-3 However, vimentin-positive cells may be occasionally depicted in most of the cases.3

Sarcomatous nodules (SNs) resemble nodules of AC at the gross level.1-3 Moreover, they are also poorly circumscribed and usually show foci of vascular invasion.1-3 Histologically, SNs may show the histologic features of fibrosarcoma or rhabdomyosarcoma or may be composed of vimentin-positive, pleomorphic, atypical, spindle-shaped cells with a high number of atypical mitotic figures, features that characterize an undifferentiated sarcoma.1-3 The differential diagnosis of SNs with nodules of AC might be achieved by the lack of immunoreactivity for cytokeratin and EMA in the spindle-shaped cells, as well as the positivity for lineage markers, such as desmin and actin.3

The most important differential diagnosis of AC is with SLNs due to the differences in their prognoses.1-3 Sarcoma-like nodules are sharply circumscribed, may be single or multiple, and usually show a red-brown to brown gross appearance.1-4 On histologic examination, these nodules are well circumscribed and composed of a heterogeneous population of cells, including epulis-type giant cells, pleomorphic mononuclear epithelioid, or spindle-shaped cells with bizarre nuclei and atypical mitotic figures.1-3,5 The presence of inflammatory cells is the rule, including histiocytes, lymphocytes, plasma cells, and polymorphs. 1-3,5 Necrosis and hemorrhage are usually observed; however, vascular invasion is uniformly absent.1-3,5 The differentiation between SLNs and nodules of AC may be achieved by the presence of noninvasive borders, highly heterogeneous cell population, and lack of vascular invasion in the former.1-3 It must be emphasized that rare cytokeratin-positive cells in an otherwise typical SLN do not warrant a diagnosis of a carcinomatous component.3

Mixed nodules are composed of an anaplastic carcinomatous component admixed with reactive changes.1-3,11 However, the existence of this category is highly disputable, since most of the nodules of AC usually show a variable component of inflammatory and reactive cells.1 Baergen and Rutgers' suggest that a nodule should be characterized as mixed only if reactive changes are the major component.1 In MNs, the presence of atypical glandular formations and positive immunoreactivity for cytokeratins and EMA in the neoplastic cells are required to characterize the carcinomatous component.1

In conclusion, we reported a case of nodules of AC arising in the walls of a mucinous multicystic tumor of borderline malignancy. We also would like to stress that pathologists must be careful not to misdiagnose SLNs as nodules of AC. This differential diagnosis might be achieved by the presence of abortive gland formations and consistent immunoreactivity for epithelial markers in the latter.

We thank Athely Pinto Guedes for typing the manuscript and for the grammar review.

References

1. Baergen RN, Rutgers JL. Mural nodules in common epithelial tumors of the ovary. Int I Gynecol Pathol. 1994;13:62-72.

2. Baergen RN, Rutgers JL. Classification of mural nodules in common epithelial tumors of the ovary. Adv Anat Pathol. 1995;2:346-351.

3. Scully RE, Young RH, Clement PB. Mucinous tumors and pseudomyxoma peritonei. In: Scully RE, Young RH, Clement PB, eds. Tumors ofthe Ovary, Maldeveloped Gonads, Fallopian Tube, and Brad Ligament. Washington, DC: Armed Forces Institute of Pathology; 1998:81-105. Atlas of Tumor Pathology; 3rd series, fascicle 23.

4. Marinho A, Nogueira R, Schmitt F, Sobrinho-Simoes M. Pancreatic mucinous cystadenocarcinoma with a mural nodule of anaplastic carcinoma. Histopathology. 1995;26:284-287.

5. Prat J, Scully RE. Ovarian mucinous tumors with sarcoma-like mural nodules: a report of seven cases. Cancer. 1979;44:1332-1344.

6. Czernobilsky B, Dgani R, Roth LM. Ovarian mucinous cystadenocarcinoma with mural nodule of carcinomatous derivation: a light and electron microscopic study. Cancer. 1983;51:141-148.

7. Chan YF, Ho HC, Yau SM, Ma L. Ovarian mucinous tumor with mural nodules of anaplastic carcinoma. Gynecol Oncol. 1989;35:112-119.

8. Sondergaard G, Kaspersen P. Ovarian and extraovarian mucinous tumors with solid mural nodules. IntJ Gynecol Pathol. 1991;10:145-155.

9. Nichols GE, Mills SE, Ulbright TM, Czernobilsky B, Roth LM. Spindle cell mural nodules in cystic ovarian mucinous tumors: a clinicopathologic and immunohistochemical study of five cases. Am J Surg Pathol. 1991;15:1055-1062.

10. Hayman JA, Ostor AG. Ovarian mucinous tumour with a focus of anaplastic carcinoma: a case report. Pathology. 1985;17:591-593.

11. Fujii S, Konishi I, Kobayashi F, Okamura H, Yamabe H, Mori T. Sarcomalike mural nodules combined with a microfocus of anaplastic carcinoma in mucinous ovarian tumor. Gynecol Oncol. 1985;20:219-233.

Jorge S. Reis-Filho, MD; Teresa M. Figueiredo, MD; Fernando C. Schmitt, MD, PhD

Accepted for publication September 14, 2001.

From the Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal (Drs Reis-Filho and Schmitt); Medical Faculty, University of Porto, Porto, Portugal (Dr Schmitt); and Federal University of Parana, Curitiba, Brazil (Dr Figueiredo).

Reprints not available from the authors.

Copyright College of American Pathologists Jul 2002
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