Case Of The Month -July 2006

Directly sampled Endometrial Adenocarcinoma

Contents

• Clinical Details
• Cytological Findings
• Histology
• Discussion
• References

Clinical Details

Mrs. N, a well-dressed, proud 65 year old is very large for her height. She often blames this on being “big boned” rather than her past obsession for chocolates and other sweet things. However now she is a type II diabetic with hypertension and no longer eats sweet things. Other than that, she is quite happy with her health. She loves collecting tropical fruit hats and makes her famous “Mrs. N's 50 secret spices chicken”. This morning she went to her GP for a routine smear. She has a normal smear history.

Cytological Findings

The sample shows a mature smear pattern, high cellularity and large amounts of well preserved glandular cell clusters having features highly suggestive of endocervical Adenocarcinoma in situ (AIS) (fig 1.2 a-c; fig 1.3). These Features such as: feathering (fig1.2c); high nuclear/ cytoplasmic ratios; nuclear overlapping and crowding (fig 1.2b); hyperchromasia of the nucleus (fig 1.1); anisokaryosis; glandular openings; granular chromatin; and syncytial structures.

Fig 1.1

4x. Hyperchromatic group in a mature smear

Fig 1.2a

10x. Hyperchromatic group in a mature smear

Fig 1.2b

40x. This group shows crowding, and pigeon tailing (or feathering).

Fig 1.2c

40x. This group shows significant feathering.

Fig 1.3

10x.

Fig 2.1

40x. This group shows more then 3 layers of thickness, syncytial formation, showing cytoplasm similar to the intermediate cell, and lack of community border.

Yet, there are also groups showing squamous morphology (fig 2.1). Hence immunocytochemistry (ICC) is carried out.

In theory, P16 and Ki67 should be strongly positive in classical case of AIS. There are 2 possible explanations for these results.

1. The immunocytochemistry reagents are not working as they should.
2. The lesion is not AIS, but a P16 and Ki67 negative malignancy.

Due to the strong cytomorphology findings the sample has been reported as AIS.

Two weeks later, a second sample was received. The second sample shows a mature smear pattern (fig 3.0), high cellularity, watery tumour diathesis (fig 3.1 a-b), well preserved 3-D clusters of cells showing features such as high nuclear/ cytoplasmic ratios, cellular crowding, multi-micronucleoli, salt and pepper chromatin, and some have cellular debris attached with hyperchromatic degenerate dysplastic cells (fig 3.2).

These features are highly suggestive of Endometrial adenocarcinoma.

Fig 3.0

10x. Dysplastic glandular group (orange arrow) with tumour diathesis (blue arrow).

Fig 3.1a

10x. This field shows a mature background and a cluster of tumour diathesis.

Fig 3.1

40x.

Fig 3.2

20x. This field shows a stream of watery tumour diathesis with small degenerate hyperchromatic dysplastic cells.

Fig 3.3a

20x.

Fig 3.3b

40x. This group pf cells show both prominent macronucleoli (green arrow) and multiple micronucleoli (purple arrow).

Fig. 3.4a

20x Half of this group is tumour diathesis (yellow arrow) , the other half is dysplastic glandular group (pink arrow):-)

Fig 3.4b

40x.

It is common to have squamous differentiation accompanied by endometrial adenocarcinoma( fig 2.1). The squamous differentiation in this case belongs to the latter category “adenosquamous carcinoma”

Histological Findings

The tissue sample shows gland formation with back-to-back and cribriform glands with small areas of necrosis. Occasional papillary structures are found. Gland-lining epithelial cells are mainly columnar. There is minor nuclear pleomorphism and some multilayering, as well some cells show cytoplasmic vacuolation.

Fig.4.1a

10x.

Fig 4.1b

40x.

Fig 4.2

40x.

Diagnosis – Features favouring endometrioid adenocarcinoma.

Discussion

Interpreting endometrial abnormalities in daily cytology often relies on spontaneous cell shedding from the endometrial lesion; therefore, the endometrial material found on cervical smears are often in small amounts and degenerate. Due to this degeneration cytomorphology is very different from that of directly sampled endometrial cells.

In cases of directly sampled endometrial adenocarcinoma the main differential diagnoses are AIS and endocervical adenocarcinoma. It is almost impossible to differentiate solely based on cytomorphology alone because both show high cellularity, hyperchromatic cell groups, glandular openings, similarity in size, large dysplastic cell sheets, community borders and syncytial structures.

Cytologic differentiation is very difficult but not impossible. With careful interpretation and attention to all the details differentiation can be achieved. Compairison of features of directly sampled endometrial adenocarcinoma (DSEMA), AIS, and endocervical adenocarcinoma (EA) are present in the table below.

At the end of the day, combination of cytological findings, histological evidence and ICC. Mrs. N. has been diagnosed with endometrial adenocarcinoma, and went on for treatment of total hysterectomy in combination of chemotherapy. Everyone in the laboratory cheers as another life is saved. Happy ever after.

References

1. DeMay R M. The Art and Science of cytopathology: Exfoliative cytology – Endometrial adenocarcinoma. ASCP Press, Chicago, 1996; 125-127.
2. Solomon D, Nayar R, et al. The Bethesda system for reporting cervical cytology: definition, criteria and explanatory notes (2^nd Ed). Springer N.Y., 2003; 147-151.

Thanks to May for submitting this case