Primary peritoneal adenocarcinoma causes pleural effusion.

CONTEXT: The most common malignancies associated with malignant pleural effusions are carcinomas of the breast, lung, gastrointestinal tract, ovary and lymphomas. Primary peritoneal adenocarcinoma is a very rare cause of malignant pleural effusion. CASE REPORT: A 72-year old female patient presented to us with shortness of breath for the last 2 months. A contrast-enhanced computed tomography (CECT) scan of her-thorax revealed only bilateral pleural effusion with absence of any mass lesion or any mediastinal lymphadenopathy. A cytologic examination of pleural fluid revealed adenocarcinoma cells. A CECT of her abdomen and pelvis revealed heterogenous thickening of omentum with nodular appearances and small amount of ascites. Her ovaries were normal and no other mass lesion was detected. A histological examination of a peritoneal lesion was suggestive of adenocarcinoma.
CONCLUSIONS: The patient was diagnosed with a rare case of primary peritoneal adenocarcinoma with bilateral pleural effusion.

Introduction

In male patients about 50% of malignant effusions are caused by lung cancer, 20% by lymphomas or leukemia, 7% from gastrointestinal primaries, 6% from genitourinary primaries, and 11% from tumors of unknown primary site. In female patients, about 40% of malignant effusions are caused by breast cancer, 20% from tumors arising in the female genital tract, 15% from lung cancer, 8% from lymphomas or leukemia, 4% from gastrointestinal tract primaries, 3% from melanoma, and 9% from tumors of unknown primary site[1].

Here we present a rare case of bilateral malignant pleural effusion which was due to primary peritoneal adenocarcinoma.

Case Report

A 72-year old female patient presented to us with shortness of breath for the last 2 months. There was no history of fever, cough, chest pain, haemoptysis, abdominal pain, vomiting or bleeding per vaginum. There was no lymphadenopathy, clubbing, or pedal edema, but pallor was present. Air entry was decreased bilaterally in the inframammary and infrascapular regions. The cardiovascular system and gastrointestinal system were normal.

The laboratory value for hemoglobin (Hb) was 8.0 g/dL. The complete blood cell count (CBC), blood sugar, renal function test and liver function test were all found to be within normal ranges. A posterior to anterior (PA) view chest X-ray (Fig. 1) was done which showed homogenous opacity in the bilateral lower lung field along with blunting of both costophrenic angles (CPA) suggestive of bilateral pleural effusion.

Fig. 1

A posterior to anterior view chest X-ray (CXR-PA) showed homogenous opacity in the bilateral lower lung field along with blunting of both costophrenic angles (CPA) suggestive of bilateral pleural effusion.

A cytologic examination of pleural fluid revealed adenocarcinoma cells (Fig 2a). A contrast-enhanced computed tomography (CECT) scan of the thorax was done which revealed only bilateral pleural effusion with absence of any mass lesion or any mediastinal lymphadenopathy (Fig. 3). An ultrasound of the abdomen and pelvis showed only ascites; no other abnormality or mass lesion was detected. A cytologic examination of ascitic fluid also revealed adenocarcinoma cells (Fig. 2b).

Fig 2(a)

Pleural fluid cytology showing tumor cells forming papillary configuration. Nuclear crowding, overlapping and acini formation (arrow) is seen suggestive of papillary adenocarcinoma (H&E X400). Fig. 2(b) Ascitic fluid cytology showing pleomorphic malignant cells, nuclear overlapping, acini formation (arrow) and cytoplasmic vacuoles in few cells suggestive of adenocarcinoma (H&E X400).

Fig. 3

A contrast-enhanced computed tomography (CECT) scan of the thorax showed bilateral pleural effusion.

A CECT scan of the abdomen and pelvis revealed heterogeneous thickening of omentum with nodular appearance and fatty streakiness into the adjacent soft tissues extending up to the anterior abdominal wall and adjacent bowel loops, including transverse and descending colon, suggestive of omental caking with small amount of ascites. The ovaries appeared normal and no other mass lesion was detected (Fig. 4).

Fig. 4

A contrast-enhanced computed tomography (CECT) scan of the abdomen and pelvis revealed heterogeneous thickening of omentum with nodular appearances.

A gynecological examination did not reveal any abnormality. An upper gastrointestinal endoscopy and colonoscopy did not show any abnormal lesion. A breast examination was normal. Examinations of the oral cavity and indirect laryngoscopy were also normal. A laparoscopic examination of the abdomen showed omental thickening along with multiple nodules on the peritoneum, but the ovaries and other organs were found to be normal. A biopsy was taken from a peritoneal lesion. A histologic examination of the biopsy was suggestive of adenocarcinoma (Fig. 5). A test for cancer antigen 125 (CA 125) showed that the level of CA 125 was elevated (3950 U/ml), but a test for carcinoembryonic antigen (CEA) was negative. The patient was diagnosed with primary peritoneal carcinoma. The patient was treated with cisplatin chemotherapy, which resulted in a decrease in tumor size, a reduction of CA 125 level, and a reduction of ascites and pleural effusion.

Fig. 5

Histopathology of the peritoneal nodular lesion showing complex branching papillary pattern (H&E X100).

Discussion

Primary peritoneal adenocarcinoma is a rare malignancy[2], which was first reported by Swerdlow in 1959[3]. It arises from the peritoneum lining the pelvis and abdomen and is characterized by disseminated intraperitoneal carcinomatosis involving the peritoneum and omentum, with normal or minimally involved ovaries, and no identifiable primary tumor. It occurs almost exclusively in menopausal and post-menopausal women and may be associated with bilateral oophorectomy for benign disease or prophylaxis[4-6]. However, a case of primary peritoneal adenocarcinoma in men was reported by Shmeuli et al[7]. Primary peritoneal adenocarcinoma is also known as serous surface papillary carcinoma[89], multiple focal extraovarian serous carcinoma[10], primary peritoneal papillary serous adenocarcinoma[11], serous surface carcinoma of the peritoneum[12], extraovarian peritoneal serous papillary carcinoma[24], normal-sized ovary carcinoma syndrome[13], papillary serous carcinoma of the peritoneum[514], and peritoneal papillary carcinoma[15].

Primary peritoneal adenocarcinoma is identical to serous ovarian carcinoma in its clinical presentation[245121415], histologic features[121617], and treatment pattern[2515], but differs from it by the presence of ovaries of normal size or ovaries that are enlarged due to a benign process, extraovarian involvement greater than ovarian involvement, and ovarian surface penetration of less than 5 mm[218]. According to Rothacker et al[19], primary peritoneal adenocarcinoma may account for 10% of the cases with a presumed diagnosis of ovarian cancer. Primary peritoneal adenocarcinoma is identical to serous ovarian carcinoma on immunochemistry[220]. Both stain positive for estrogen receptor (ER), cytokeratin 7 (CK7), Wilm's tumor suppressor gene (WT1), and cancer antigen 125 (CA 125), but negative for cytokeratin 20 (CK 20), progesterone receptor (PR), calretinin, carcinoembryonic antigen (CEA), gross cystic disease fluid protein (BRST-2), and thyroid transcription factor 1 (TTF1). Primary peritoneal adenocarcinoma shows widespread intraperitoneal carcinomatosis, usually involving the omentum and upper abdomen, and can be misdiagnosed as peritoneal carcinomatosis from metastatic gastrointestinal cancers or ovarian cancer. However, it can be differentiated by no or minimal involvement of the ovaries and by no primary lesion in the gastrointestinal tract or other organs. Extraovarian primary peritoneal carcinoma spreads mainly transperitoneally; but lymphatic and blood-borne metastases have also been reported[45]. Metastases to the liver[5], brain[21], and lymph node[45] have been reported. In primary peritoneal adenocarcinoma, the level of CA 125 is found to be elevated and correlates with the clinical status of the disease and response to therapy[1114]. The most common presenting symptoms include abdominal distension, pain, nausea, vomiting, dyspepsia, or change in bowel habits. The most common finding on physical examination is ascites. Interestingly, our patient presented with massive bilateral pleural effusion, which is unusual in presence of small amount of ascitis as pleural involvement is a rare event[22].The histological picture is characterized by a predominantly serous pattern[451123], but non serous types such as mucinous[24], clear cell[25], endometrioid[26], and mixed müllerian tumors have also been reported[27].

Patients with primary peritoneal carcinoma are treated by cytoreductive surgery followed by cisplatin-based chemotherapy. This treatment is similar to the treatment of ovarian carcinoma and the response achieved by this treatment is also similar to that achieved in ovarian carcinoma[2515]. A cisplatin-based chemotherapy regimen is the most common first-line chemotherapeutic regimen used in primary peritoneal carcinoma[245111415]. Patients treated by cisplatin-based regimens have a longer survival compared to other chemotherapy regimens[5]. At the same time, patients treated with combination chemotherapy regimens show longer survival compared to single agent regimens. Patients who undergo optimal cytoreductive surgery show significantly higher response rates to chemotherapy as well as increased survival rates compared to patients for whom optimal cytoreductive surgery was not achievable[28].The grade of tumor does not appear to affect the response to chemotherapy[29]. Patients with primary peritoneal carcinoma have poor survival rates. The median survival time varies between 7.0 and 27.8 months, while 5-year survival rates range from 0% to 26.5%[245142930]. The survival rate of patients with primary peritoneal carcinoma is poorer than the survival rate of patients with serous ovarian cancer[414].

Conclusion

The diagnosis of primary peritoneal adenocarcinoma should be considered in elderly female patients with malignant pleural effusion containing adenocarcinoma cells if intraperitoneal carcinomatosis is found, but no primary tumor is identified.