Micropapillary carcinoma (MPC) is an uncommon morphology typically observed within the context of the borderline serous carcinoma of the ovary (1). In addition, similar morphological characteristics of MPC are rarely detected in other non-ovarian sites, such as the breast, urinary bladder, lung, parotid glands and colon (2–7). In anatomical locations other than the ovaries, MPC exhibits an aggressive course and generally accompanies the primary neoplasm of the organ of its origin (2).

Histologically, MPC has a typical appearance, characterized by cells with eosinophilic cytoplasm that exhibits a nest-like arrangement in artifactual spaces. The appearance is reminiscent of enlarged angiolymphatic vessels and is associated with a more aggressive clinical course and a higher rate of lymph node metastasis compared with the typical carcinomas of the organ of origin. Regardless of the accompanying tumor, the majority of MPC must always be documented in the pathological diagnosis.

Although less well characterized than its histological features, the cytological features of MPC have also been well defined. This is predominantly due to the increasing use of fine needle aspiration (FNA) biopsy, particularly in the parenchymal organs, which allows earlier diagnosis of this aggressive tumor (8–10). The early diagnosis of MPC with FNA biopsy may also be useful in uncommon sites, such as the parotid gland and pericardium.

In parenchymal organs, such as the breast, lung and parotid glands, where FNA has a major diagnostic role, it is important to be aware of MPC as a disease entity and to document its presence. Special care must be provided when evaluating lymph node and serous surface aspirations, due to their high tendency toward angiolymphatic spread and metastasis.

The current study assessed the cytological characteristics and emphasized the diagnostic value of the cytological examination of MPC in a total of eight cases with histologically confirmed diagnoses of pure MPC occurring at different sites, including the breast, urinary bladder, pericardium and parotid gland. The patient provided written informed consent.

In addition to borderline serous carcinoma of the ovary, MPC has also been identified in other sites, such as the stomach, colon and parotid gland, over the last two decades (2–10). Despite its rarity, it deserves extra attention by virtue of its aggressive course. MPC coexisting with other morphological types of primary adenocarcinoma is more common than pure MPC. It may also initially present as distant metastasis due to a high rate of vascular invasion. The reverse polarity (inside-out growth) is the typical histological characteristic of the tumor that is likely to be essential in its pathogenesis. The direct contact between the secretory surface and the surrounding stroma is also likely to facilitate disease spread (2–10,12).

As emphasized previously, the early diagnosis of MPC is extremely important due to its aggressive course and, therefore, FNA and other cytological biopsy techniques have a major role in early diagnosis and management. FNA is a relatively easy biopsy method with a number of documented cases of breast MPC diagnosed using this approach (10,13,14). However, few cases of MPC in the urinary bladder have been reported, possibly due to the inapplicability of FNA and the availability of urine as the only cytological sample (15,16). Although an increased number of studies examining the role of cytological examination in the lung have been conducted compared with those in the urinary bladder (17), to the best of our knowledge, no cases of primary MPC in the parotid gland or MPC in the lungs presenting with pericardial findings have been previously reported.

MPC usually exhibits similar characteristics in all organs, which assists in the diagnosis. General cytological features of MPC are as follows: i) Background consists of mucin, tumor diathesis and particularly urine smear with a dirty background, including numerous inflammatory cells; ii) cell clusters include tight clusters, three-dimensional cell aggregates with high grade nuclear features, morula, cell balls, staghorn structures and cell clusters with scalloped borders; and iii) cytological findings comprise cells with a high nuclear/cytoplasmic ratio, dense cytoplasm, moderate to severe nuclear atypia, including some vacuolated cells and apocrine-like cells, scattered single cells with columnar configuration and eccentric nuclei

In the majority of the present eight cases, the aforementioned cytological characteristics were present. The most frequent cytological findings were three-dimensional aggregates with high-grade nuclear features, cell clusters with angulated or scalloped borders, and single cells with columnar configuration and eccentric nuclei. In addition, single apocrine-like cells were more frequent in the breast samples.

All of the cases had pure MPC and a malignant cytology was readily established. A diagnosis of malignancy is easier to establish than a direct diagnosis of MPC in cytological materials, particularly in the breast. The histological characteristics of the neoplasm accompanied by MPC and additional features, including the dirty mucinous background, marked nuclear pleomorphism, discohesive cell groups, single cells, and inability to observe the surrounding myoepithelial cells in the breast FNA, assist in a diagnosis of malignancy. However, a diagnosis of pure MPC may not be readily determined and requires a good knowledge of its cytology. MPC of the bladder is uncommon; studies describing its cytological features are rare (8,15,16).

Although its cytological features do not differ from those of MPCs in other organs, the differential diagnosis from high-grade urothelial carcinomas may be difficult. Three cases of bladder MPC in the current series had a diagnosis of malignant cytology; only the eighth case was determined as an MPC. The most distinguishing feature of this case was the sharp, distinctive borders of the cell clusters. This case was the micropapillary variant of in situ urothelial carcinoma. In situ MPC is less aggressive than its invasive counterpart; its course is similar to that of urothelial carcinoma and may progress (18).

Parotid aspiration in the present study showed characteristics of an in situ ductal carcinoma rather than the typical characteristics of invasive MPC. In addition, histological examination revealed a predominance of in situ ductal carcinoma (solid and micropapillary). The invasive component exclusively consisted of MPC. MPC in the parotid glands is extremely rare with only a few previous cases reported (6,19), and the current study presents the first report with cytological findings. In suspected cases of ductal adenocarcinoma of the parotid gland, the possibility of MPC must also be considered.

Furthermore, to the best of our knowledge, the presented case of lung MPC with initial pericardial presentation represents the first of such a case in the literature. As compared with the pleura, the pericardium is a less frequent site of metastasis. This patient with chest pain presented to Namık Kemal University Medical Center (Tekirdağ, Turkey) and a pericardial aspiration was performed. The microscopic slides were then referred to the Department of Pathology, Istanbul Education and Research Hospital for consultation. Initially, it was not possible to differentiate between mesothelioma and metastasis due to the cytological similarity between these two conditions. However, following the detection of a mass lesion in the radiological imaging studies, a biopsy was performed with a subsequent diagnosis of MPC. This suggests that MPC must be included in the differential diagnosis of less common metastasis sites, such as the pericardium.

It is important to recognize the well-defined cytological characteristics of MPC to determine a precise diagnosis. A malignant condition with high metastatic potential, such as MPC, may occur in extremely rare sites, including the parotid glands, or initially present on serous surfaces, such as the pericardium.