Case 6

View the images and select the correct diagnosis from the list below.

Clear as mud

Pap smear from an 81-year-old woman with a two-month history of suprapubic pain and a history of invasive cervical squamous cell carcinoma treated with radiation:

Select the correct diagnosis:

A) Endometrial adenocarcinoma with squamous differentiation

You answered: Endometrial adenocarcinoma with squamous differentiation
Sorry, that is INCORRECT

The correct diagnosis is: Clear cell carcinoma of the endometrium

CYTOPATHOLOGY:

The smear contains loosely cohesive sheets and single atypical cells that have abundant finely vacuolated, clear cytoplasm.
In some groups, cells have a linear arrangement suggesting a glandular pattern.
The nuclei are enlarged, eccentric in the cell, have smooth nuclear outlines and show some variation in size.
The cytologic findings suggest clear cell adenocarcinoma.
Squamous cell carcinoma would be expected to show cells with enlarged, hyperchromatic, pleomorphic nuclei and coarse, irregular chromatin.
Given the history, reactive/radiation change may be a consideration. The smear does show a squamous component with mixed maturation, including many cells with benign atrophic changes and hyperkeratosis. Although vacuoles are common in radiation change, they usually involve both nucleus and cytoplasm, are degenerate in appearance and are associated with multinucleation and polychromatophilia.

DISCUSSION:

The endometrial curettings reveal malignant glands with a tubular pattern lined by deceptively bland cells with clear cytoplasms typical of clear cell adenocarcinoma.
Although clear cell carcinoma often reveals cells with high grade nuclei, hobnail cells and intracytoplasmic hyaline globules, these are not seen in this case.
Clear cell adenocarcinomas may have tubulocystic, papillary or solid growth patterns.
Cell clearing is due to glycogen.
Approximately 3-6% of endometrial carcinomas are clear cell carcinomas. Endometrioid endometrial adenocarcinoma and endometrial clear cell adenocarcinoma have similar clinical presentations, although the typical mean age is older in patients with clear cell carcinomas than with endometrioid carcinoma (67 vs. 59 years).
Prior pelvic irradiation may be a contributing factor in the pathogenesis of clear cell adenocarcinoma.

BACK TO IMAGES

HISTOLOGY

REFERENCES:

DeMay RM. The Art & Science of Cytopathology. Chicago: ASCP Press, 1996: 125-7.

Robboy SJ, Anderson MC, Russel P. Pathology of the Female Reproductive Tract. London: Churchill Livingstone, 2002: 348-9.

Clement PB, Young RH. Atlas of Gynecologic Surgical Pathology. Philadelphia: W.B. Saunders Company, 2000: 98-9, 314-17.

B) Squamous cell carcinoma

You answered: Squamous cell carcinoma
Sorry, that is INCORRECT

The correct diagnosis is: Clear cell carcinoma of the endometrium

CYTOPATHOLOGY:

The smear contains loosely cohesive sheets and single atypical cells that have abundant finely vacuolated, clear cytoplasm.
In some groups, cells have a linear arrangement suggesting a glandular pattern.
The nuclei are enlarged, eccentric in the cell, have smooth nuclear outlines and show some variation in size.
The cytologic findings suggest clear cell adenocarcinoma.
Squamous cell carcinoma would be expected to show cells with enlarged, hyperchromatic, pleomorphic nuclei and coarse, irregular chromatin.
Given the history, reactive/radiation change may be a consideration. The smear does show a squamous component with mixed maturation, including many cells with benign atrophic changes and hyperkeratosis. Although vacuoles are common in radiation change, they usually involve both nucleus and cytoplasm, are degenerate in appearance and are associated with multinucleation and polychromatophilia.

DISCUSSION:

The endometrial curettings reveal malignant glands with a tubular pattern lined by deceptively bland cells with clear cytoplasms typical of clear cell adenocarcinoma.
Although clear cell carcinoma often reveals cells with high grade nuclei, hobnail cells and intracytoplasmic hyaline globules, these are not seen in this case.
Clear cell adenocarcinomas may have tubulocystic, papillary or solid growth patterns.
Cell clearing is due to glycogen.
Approximately 3-6% of endometrial carcinomas are clear cell carcinomas. Endometrioid endometrial adenocarcinoma and endometrial clear cell adenocarcinoma have similar clinical presentations, although the typical mean age is older in patients with clear cell carcinomas than with endometrioid carcinoma (67 vs. 59 years).
Prior pelvic irradiation may be a contributing factor in the pathogenesis of clear cell adenocarcinoma.

BACK TO IMAGES

HISTOLOGY

REFERENCES:

DeMay RM. The Art & Science of Cytopathology. Chicago: ASCP Press, 1996: 125-7.

Robboy SJ, Anderson MC, Russel P. Pathology of the Female Reproductive Tract. London: Churchill Livingstone, 2002: 348-9.

Clement PB, Young RH. Atlas of Gynecologic Surgical Pathology. Philadelphia: W.B. Saunders Company, 2000: 98-9, 314-17.

C) Clear cell carcinoma of the endometrium

You answered: Clear cell carcinoma of the endometrium

That is CORRECT!!

CYTOPATHOLOGY:

The smear contains loosely cohesive sheets and single atypical cells that have abundant finely vacuolated, clear cytoplasm.
In some groups, cells have a linear arrangement suggesting a glandular pattern.
The nuclei are enlarged, eccentric in the cell, have smooth nuclear outlines and show some variation in size.
The cytologic findings suggest clear cell adenocarcinoma
Squamous cell carcinoma would be expected to show cells with enlarged, hyperchromatic, pleomorphic nuclei and coarse, irregular chromatin.
Given the history, reactive/radiation change may be a consideration. The smear does show a squamous component with mixed maturation, including many cells with benign atrophic changes and hyperkeratosis. Although vacuoles are common in radiation change, they usually involve both nucleus and cytoplasm, are degenerate in appearance and are associated with multinucleation and polychromatophilia.

DISCUSSION:

The endometrial curettings reveal malignant glands with a tubular pattern lined by deceptively bland cells with clear cytoplasms typical of clear cell adenocarcinoma.
Although clear cell carcinoma often reveals cells with high grade nuclei, hobnail cells and intracytoplasmic hyaline globules, these are not seen in this case.
Clear cell adenocarcinomas may have tubulocystic, papillary or solid growth patterns.
Cell clearing is due to glycogen.
Approximately 3-6% of endometrial carcinomas are clear cell carcinomas. Endometrioid endometrial adenocarcinoma and endometrial clear cell adenocarcinoma have similar clinical presentations, although the typical mean age is older in patients with clear cell carcinomas than with endometrioid carcinoma (67 vs. 59 years).
Prior pelvic irradiation may be a contributing factor in the pathogenesis of clear cell adenocarcinoma.

BACK TO IMAGES

HISTOLOGY

REFERENCES:

DeMay RM. The Art & Science of Cytopathology. Chicago: ASCP Press, 1996: 125-7.

Robboy SJ, Anderson MC, Russel P. Pathology of the Female Reproductive Tract. London: Churchill Livingstone, 2002: 348-9.

Clement PB, Young RH. Atlas of Gynecologic Surgical Pathology. Philadelphia: W.B. Saunders Company, 2000: 98-9, 314-17.

D) Reactive cellular changes associated with radiation

You answered: Reactive cellular changes associated with radiation
Sorry, that is INCORRECT

The correct diagnosis is: Clear cell carcinoma of the endometrium

CYTOPATHOLOGY:

The smear contains loosely cohesive sheets and single atypical cells that have abundant finely vacuolated, clear cytoplasm.
In some groups, cells have a linear arrangement suggesting a glandular pattern.
The nuclei are enlarged, eccentric in the cell, have smooth nuclear outlines and show some variation in size.
The cytologic findings suggest clear cell adenocarcinoma.
Squamous cell carcinoma would be expected to show cells with enlarged, hyperchromatic, pleomorphic nuclei and coarse, irregular chromatin.
Given the history, reactive/radiation change may be a consideration. The smear does show a squamous component with mixed maturation, including many cells with benign atrophic changes and hyperkeratosis. Although vacuoles are common in radiation change, they usually involve both nucleus and cytoplasm, are degenerate in appearance and are associated with multinucleation and polychromatophilia.

DISCUSSION:

The endometrial curettings reveal malignant glands with a tubular pattern lined by deceptively bland cells with clear cytoplasms typical of clear cell adenocarcinoma.
Although clear cell carcinoma often reveals cells with high grade nuclei, hobnail cells and intracytoplasmic hyaline globules, these are not seen in this case.
Clear cell adenocarcinomas may have tubulocystic, papillary or solid growth patterns.
Cell clearing is due to glycogen.
Approximately 3-6% of endometrial carcinomas are clear cell carcinomas. Endometrioid endometrial adenocarcinoma and endometrial clear cell adenocarcinoma have similar clinical presentations, although the typical mean age is older in patients with clear cell carcinomas than with endometrioid carcinoma (67 vs. 59 years).
Prior pelvic irradiation may be a contributing factor in the pathogenesis of clear cell adenocarcinoma.

BACK TO IMAGES

HISTOLOGY

REFERENCES:

DeMay RM. The Art & Science of Cytopathology. Chicago: ASCP Press, 1996: 125-7.

Robboy SJ, Anderson MC, Russel P. Pathology of the Female Reproductive Tract. London: Churchill Livingstone, 2002: 348-9.

Clement PB, Young RH. Atlas of Gynecologic Surgical Pathology. Philadelphia: W.B. Saunders Company, 2000: 98-9, 314-17.

Histology

From the Cytopathology files of BC Cancer
Submitted by: Gwen Ross, BSc and Tom Thomson, MD
with assistance from Brenda Smith, BSc.