Dear Editor,
Mixed surface epithelial malignancies of the ovary most commonly involve endometrioid
and clear cell components, likely due to their shared clonal origin from endometriotic
precursors.[1] Also, squamous differentiation is more commonly observed in endometrioid adenocarcinomas
of the ovary and is exceedingly rare in other surface epithelial subtypes.[2] A thorough literature review on PubMed revealed only four reported cases of ovarian
serous carcinoma with squamous differentiation, all of which involved pure serous
tumors.[3]
[4]
[5] Other reports have described primary ovarian squamous cell carcinomas arising from
precursor lesions such as ovarian teratomas or endometriosis.[6] Hence, the biological behavior of high-grade serous carcinoma (HGSC) with squamous
differentiation remains poorly defined. The present case features a highly unusual
combination of HGSC and clear cell carcinoma with serous component exhibiting extensive
squamous differentiation by morphology and later confirmed by immunohistochemistry
(IHC).
A 60-year-old female patient presented with lower abdominal pain and discomfort. Magnetic
resonance imaging of the pelvis performed at an external facility showed a large,
fairly well-defined mass lesion with a predominant cystic component and multiple peripheral
solid enhancing components in the pelvis, arising from the left adnexa, superior to
the uterus and extending into the lower abdomen. Both the ovaries were not seen separately.
Metastatic right common iliac and left para-aortic lymph nodes were also seen. Hence,
a diagnosis of stage II ovarian carcinoma was given. Serum CA125 levels were high
(157 U/mL).
She was then referred to our hospital for further management and underwent staging
laparotomy. Intraoperatively, peritoneum was seen densely adherent to the anterior
abdominal wall, uterus, and the pelvic mass. A controlled decompression of the mass
was done to facilitate resection. The mass was removed in total and type A radical
hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and bilateral pelvic
and para-aortic lymph node dissection was done after identifying and preserving bilateral
ureters and separating the rectum that was densely adherent to the posterior wall
of the uterus and the mass.
Gross examination revealed tubo-ovarian masses measuring 6.0 × 5.0 × 4.0 cm on one
side and 5.5 × 3.0 × 3.0 cm on the other. The external surfaces of both ovaries were
adherent to the peritoneum and the laterality of the bilateral adnexa could not be
made out. One side ovary displayed solid areas and a cyst filled with necrotic and
friable material. The contralateral ovary appeared entirely solid, gray-yellow, and
necrotic.
Microscopically, two distinct malignant epithelial components were identified: 60%
of tumor showed serous carcinoma with cells arranged in papillae, solid nests, and
sheets with extensive necrosis and neutrophilic abscess formation. Notably, portions
of the HGSC component exhibited morphological features mimicking high-grade squamous
cell carcinoma, characterized by polygonal to spindle-shaped cells with dense eosinophilic
cytoplasm and hyperchromatic nuclei with prominent individual cell keratinization.
Note that 40% showed clear cell component with a tubulocystic pattern. The cells were
cuboidal and have clear to eosinophilic cytoplasm, vesicular nuclei, and prominent
nucleoli; occasional hobnailing was also noted. Examination of the fallopian tube
revealed tumor arising from the tubal epithelium with stromal invasion, excluding
the possibility of metastatic origin. Tumor deposits were also noted on the ovarian
capsule and pelvic peritoneum.
IHC revealed diffuse PAX8 and p16 (block-type) positivity in the serous component
with focal WT1 positivity, and a p53 mutant pattern with strong nuclear staining.
The clear cell component showed patchy cytoplasmic granular positivity for Napsin
A and diffuse PAX8 and p16 positivity. The squamous component demonstrated diffuse
positivity for p63 and CK5/6, focal positivity for PAX8, and negative for estrogen
receptor.
Based on histological and immunophenotypic features, a final diagnosis of bilateral
mixed ovarian carcinoma comprising HGSC (60%) and clear cell carcinoma (40%) with
extensive squamous differentiation was rendered. The patient underwent six cycles
of adjuvant chemotherapy and was disease free at 1-year follow-up.
