Direct sampling of metastatic ovarian carcinoma masquerading as endocervical adenocarcinoma in liquid-based cytology cervical sample.

Cervical sample is routinely taken to identify squamous dysplastic lesions of the cervix. Glandular lesions are far less commonly reported on cervical samples. The most common glandular lesion reported on cervical smear is endocervical adenocarcinoma, followed by endometrial adenocarcinoma. Direct sampling by Cervex brush is possible even in endometrial adenocarcinoma, if the tumor directly involves lower uterine segment/endocervical canal. Metastases to cervix are rare but have occasionally been reported in previous reports. We wish to highlight in this case, metastatic ovarian carcinoma directly sampled in cervical liquid-based cytology (LBC) sample, which mimicked cytomorphologically a well-differentiated endocervical adenocarcinoma. To the best of our knowledge, a similar case has not been previously published in SurePath LBC sample.

Introduction

Extra-uterine tumors are rarely known to metastasize to cervix. The most common extra-uterine tumors include ovarian and fallopian tubal carcinomas.[1] Lobular carcinoma of the breast, lung carcinoma, gastrointestinal tumors, and malignant melanoma are other rare tumors known to metastasize to the cervical region. Tumor cells from such malignancies are rarely seen in the cervical Pap samples. A detailed clinical history, knowledge of the previous primary tumor and cytomorphologic features helps in correct identification of these tumors. Direct sampling of endometrial carcinoma and rarely other metastatic tumors can result in cytomorphology similar to that of endocervical adenocarcinoma. Endocervical adenocarcinoma usually represents in cervical liquid-based cytology (LBC) samples by the presence of numerous tall columnar glandular cells showing nuclear atypia. The nuclei in these cells are elongated to cigar-shaped with strips of endocervical type of cells showing nuclear feathering. Similar cellular features were identified in the present case of metastatic ovarian carcinoma to cervix due to direct sampling of the tumor in LBC cervical sample. To the best of our knowledge, similar case of direct sampling of metastatic ovarian carcinoma in SurePath LBC Pap sample has not been reported previously.

Case Report

A routine cervical sample was taken in a 50-year-old postmenopausal female. The “split cervical sample” was taken with Cervex brush and a conventional smear was also prepared before dropping the brush head in SurePath® LBC vial. Both the conventional as well as SurePath® cervical samples were processed and stained with Papanicolaou stain. The smears revealed numerous clusters as well as scattered atypical glandular cells. LBC sample showed a large number of glandular cells, which were present as short strips, small clusters, hyperchromatic crowded cell groups, and as scattered cells [Figure 1a]. The cells in short strips showed prominent nuclear bulging. The cells were tall columnar showing oval to cigar-shaped nuclei with moderate nuclear pleomorphism, coarse granular chromatin and one to two conspicuous nucleoli [Figure 1b and c]. Cytological features indicating tumor diathesis were noted in the form of fibrin threads with clinging tumor cells, polymorphs and nuclear debris. Conventional smear also revealed clusters of atypical glandular cells [Figure 1d]. Based on cytomorphological features, a diagnosis of endocervical adenocarcinoma was suggested on cervical sample. On per-vaginum examination, 2 cm × 2 cm polypoidal growth was identified at the cervical os and a cervical biopsy was taken. The histopathological examination of cervical biopsy confirmed the presence of a moderately-differentiated adenocarcinoma [Figure 2a and b]. Serum CA-125 level was raised. The patient underwent an exploratory laparatomy and a total abdominal hysterectomy with bilateral salpingo-oöpherctomy, omentectomy and peritoneal washing. Peritoneal washing showed a metastatic adenocarcinoma. On gross examination, the ovarian tumor was 6 cm × 4 cm × 4 cm in size, solid with smooth capsular surface. The ovarian tumor was confirmed to be a high-grade papillary serous carcinoma on microscopic examination [Figure 2c and d]. A small lesion in the endocervix was identified as metastatic ovarian tumor which was directly sampled in cervical sample leading to misdiagnosis of cervical adenocarcinoma. Immunostaining for WT-1, p53, p16, and carcinoembryonic antigen (CEA) was performed on the cervical biopsy to exclude endocervical adenocarcinoma. The tumor cells were negative for p16 and CEA and were positive for p53 and WT-1 suggesting ovarian origin. This case highlights that the cytopathologist should be cautious about the fact that cytomorphological features of directly sampled metastatic tumors mimic those of endocervical adenocarcinoma.

Figure 1

Microphotographs showing cervical Pap sample. (a) Highly cellular smear with clusters, strips and singly scattered tall columnar glandular cells (liquid based cytology [LBC] Pap, ×200). (b) A thick cluster of atypical glandular cells showing round to oval nuclei, nuclear pleomorphism and conspicuous nucleoli (LBC Pap, ×400). (c) About 3-4 cell thick cluster of atypical glandular cells showing nuclear pleomorphism and prominent nucleoli (LBC Pap, ×1000). (d) A cluster of atypical glandular cells in conventional Pap smear (Pap, ×400)

Figure 2

Microphotograph showing histopathology of the tumor. (a) Cervical biopsy showing stratified squamous lining on one side, dense mixed inflammation and an occasional dilated gland lined by atypical glandular cells (H and E, ×200). (b) Another fragment of cervical biopsy showing a papillary serous adenocarcinoma (H and E, ×400). (c) Ovarian tumor showing similar papillary serous adenocarcinoma with a fibrous capsule (H and E, ×200). (d) Ovarian tumor showing similar papillary serous adenocarcinoma (H and E, ×400)

Discussion

Ovarian and fallopian tubal carcinomas are known to shed tumor cells in cervical Pap samples rarely.[1] There are previous reports which stress on higher detection rates of glandular abnormalities in cervical samples with introduction of liquid based cytology. This has partially been related to better sampling devices, improved and uniform cellular presentation and cellular preservation.[1] The cytomorphologic features of the shed ovarian or tubal tumor cells are distinct from endocervical adenocarcinoma and adenocarcinoma in-situ (AIS). These tumor cells of ovarian or tubal origin are usually seen as three-dimensional ball-like clusters with or without associated psammoma bodies. The nuclear features are particularly helpful in diagnosing these cases as malignant. Typical features associated with AIS and endocervical adenocarcinoma include strips and small clusters of endocervical type of tall columnar cells showing prominent feathering, fanning-out with bird-tail appearance. The cells have oval to cigar-shaped nuclei which tend to appear bulging out of the cell giving a “snake and egg appearance”. Tumor diathesis may be noted in LBC samples with the presence of fibrin-like material with entangled polymorphonuclear cells and clinging tumor cells. The cellular arrangement, pattern of cell spread and the background of the smear helps in diagnosing the origin of tumor cells involving the cervix.[2] Extra-uterine malignancies are also known to metastasize in the cervix and are rarely detected in cervical samples.[3] We wish to highlight in this report that a metastatic tumor to cervix or tumor involving endocervical canal can lead to direct sampling of the tumor by the endocervical brush or Cervex brush used for taking cervical sample. Direct sampling of tumors can lead to the cytological features of glandular cells which mimic AIS or endocervical adenocarcinoma. Subtle differences such as absence of true feathering or fanning-out of columnar cells, few three-dimensional papillary clusters and nuclear atypia more than that expected in AIS may point toward the presence of a metastatic tumor rather than AIS. It is important to consider the possibility of metastases at the time of reporting an LBC cervical sample so as to avoid misdiagnosis.[45] To the best of our knowledge, this is the first case of SurePath® LBC sample showing directly sampled metastatic ovarian tumor masquerading as endocervical adenocarcinoma. Another such case has been published showing glandular cells of ovarian origin in ThinPrep® sample.[6] This case highlights that the pathologist should be aware of the possibility of cervical mucosal metastasis to avoid an erroneous diagnosis of a primary cervical adenocarcinoma or AIS.