Case Of The Month -March 2006

POORLY DIFFERENTIATED CARCINOMA-
PROBABLY AN ADENOSQUAMOUS CARCINOMA

Contents

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

Clinical Details

A routine cervical smear is obtained from a 39-Year-old female patient with no prior smear history.

Cytological Findings

The original diagnosis was that of HGSIL. Upon review, the smear was diagnosed as adenocarcinoma with a HGSIL component. As seen in images 1, 2 &3, there are synctial-like groups with scant vacuolated cytoplasm, coarse chromatin, variation in nuclear size and prominent nucleoli. It should also be noted that these groups are less than three layers thick. The nuclei have smooth borders and are 2x the size of an intermediate nucleus. There is a loss of polarity; however, loose acinar formations exist as in demonstrated in image 3. Image 4 reveals a single cell with coarse chromatin and an obvious macronucleoli.

The squamous component of this smear is seen in images 5&6. Both pictures show an increased n/c ratio with image 6 exhibiting nuclear enlargement 5x that of an intermediate nucleus, and a prominent nucleoli. Both of these images are suggestive of a HGSIL. Image 7 displays small nuclei, 1- 1.5x that of an intermediate nucleus, with some moulding and scant delicate cytoplasm. This group arouses the suspicion of a small cell neuroendocrine tumour.

Cyto Image 1 of 7

Cyto Image 2 of 7

Cyto Image 3 of 7

Cyto Image 4 of 7

Cyto Image 5 of 7

Cyto Image 6 of 7

Cyto Image 7 of 7

Histology

Sections show large fragments of tumour composed predominantly of sheets and strands of malignant epithelial cells showing prominent apoptosis, numerous mitoses and containing cytoplasm ranging from clear to slightly eosinophilic. Occasional glandular formations are noted and scattered cells shows cytoplasmic eosinophilia. Tumour cells are set within a stroma displaying a strong fibroblastic response. A tiny fragment of high grade dysplastic squamous epithelium is seen in one area, beneath which two small islands of the epithelial cells (See Histo Image 1). Immunohistochemical stains show positive staining for CK-7, CEA and DPAS with negative staining for CK-20, chromogranin and synaptophysin. Features are those of a poorly differentiated carcinoma probably an adenosquamous carcinoma. (See Immunohistochemistry: image Histo 2, which demonstrates a positive DPAS- mucin stain as noted by the magenta colour in the centre of the apparent gland formation.)

Histo Image 1 of 2

Histo Image 2 of 2

Immunohistochemistry

Immunohistochemical staining has given the following results:

Mintzer, Warhol, Martin and Greene ^[1]

Discussion

Despite the occasional HGSIL cells, the majority of cytological evidence leans towards that of an adenocarcinoma. The acinar formations, smooth nuclear borders, vacuolated cytoplasm and prominent nucleoli are features generally associated with glandular lesions; whereas, the coarse chromatin, variation in nuclear size and loss of polarity are inconclusive.

It is easy to presume that there is a homogenous abnormality that is either glandular or squamous; however adenocarcinomas and squamous carcinomas can and do co-existent. It is also true that "poorly differentiated cancers may demonstrate characteristics of both squamous and glandular lesions" Demay ^[2].

The small nuclei with molding and scant cytoplasm, make neuroendocrine tumours a possibility that must be ruled out. The negative response to the chromogranin and synaptophysin immunohistochemistry stains clearly dismisses this possibility. The positive CK7 and negative CK20 expression, according to Wang et al.^[3] and Chu et al. ^[4] is indicative of several adenocarcinomas. The most likely in this circumstance would be endometrial carcinoma. This amalgamated; with positive CEA and DPAS staining suggests the possibility of a mucinous adenocarcinoma. These results combined with the cytological findings highly suggests an adenocarcinoma. Due to the cytological and histological evidence of minute sections of HGSIL, the final report is that of a poorly differentiated carcinoma- probably an adenosquamous carcinoma.

References

1. David M. Mintzer, Michael Warhol, Anne-Marie Martin, Gary Greene. Cancer of Unknown Primary: Changing Approaches. A Multidisciplinary Case Presentation from the Joan Karnell Cancer Center of Pennsylvania Hospital. The Oncologist 2004;9:330 -338.
2. Richard M DeMay; Practical Principles of Cytopathology; ASCP; 21-22; 1999.
3. Wang NP, Zee S, Zarbo RJ et al. Coordinate expression of cytokeratins 7 and 20 define unique subsets of carcinoma. Appl Immunohistochem Mol Morphol 1995;3:99-107.
4. Robert J. Kurman, Diane Solomon; Springer-VerlagThe Bethesda System.;48; 1994.

Thanks to Rhonda for submitting this case