Metastatic micropapillary adenocarcinoma in cervix revealing an occult primary in breast

Dear Editor, Metastatic tumors in the cervix represent less than 2% of metastasis to the female genital tract and 0.3% of all cervical tumors. Cervical malignancy revealing an occult primary breast tumor is exceedingly rare with only a handful of case reports in the world literature.[1,2] A 52-year-old female presented with right hemiparesis for 10 months duration and intermittent vaginal bleeding for 1 month. Gynecological examination revealed a 4 cm ulceroproliferative cervical growth. Magnetic resonance imaging (MRI) of the brain and cervical spine revealed multiple lesions in the brain, and cervico-dorsal spine, suggestive of metastasis. Whole body positron emission tomography-computed tomography (PET-CT) suggested cervical growth with metabolically active extensive brain and bony lesions. No other significant metabolically active disease was seen elsewhere in the body. A clinical diagnosis of carcinoma cervix with brain metastasis was made. Biopsy from cervical growth revealed a tumor in the micropapillary configuration. Individual cells were polygonal with round, vesicular nuclei, prominent nucleoli, and abundant cytoplasm, with no squamoid features, suggesting an adenocarcinoma with micropapillary pattern (an uncommon pattern for cervical adenocarcinomas) [Figure 1].Figure 1: (a) Cervical stroma infiltration by adenocarcinoma with micropapillary configuration and lymph vascular invasion (thick arrow). Overlying squamous epithelium is unremarkable (thin arrow) (H and E, × 200). (b) Tumor cells show marked nuclear atypia and pleomorphism with coarse chromatin and conspicuous nucleoli (H and E stain)On immunohistochemistry (IHC) [Figure 2], the tumor cells expressed CK 7, while were negative for p40, WT-1, p16, and PAX-8. Epithelial membrane antigen showed reverse polarity expression patterns. Further IHC revealed strong positivity for GATA-3 and mammaglobin, while negativity for uroplakin III and CK20, strongly pointing towards the primary tumor in breast. The case was discussed in a multispeciality tumor board, and PET-Scan was reviewed in which a vague thickened lesion was identified in the retroareolar region of the left breast. Biopsy from breast lesion confirmed a grade 2 invasive duct carcinoma with ~10% areas with micropapillary pattern [Figure 3]. A final diagnosis of carcinoma breast with cervical and brain metastasis was rendered. The breast tumor showed estrogen receptor (ER) expression in 90% cells (strong intensity), progesterone receptor (PR) in 80% (strong intensity), and HER2 was negative.Figure 2: On immunohistochemical staining, the tumor cells show diffuse strong staining for CK7 (a), positive staining for epithelial membrane antigen (EMA) in the periphery of tumor nests suggestive of an "inside-out" morphology (b), strong nuclear expression for GATA-3 (c), and patchy strong cytoplasmic expression of mammaglobin indicating metastasis from tumor in breast (d). (IHC stain with DAB)Figure 3: (a) FDG PET-CT image revealed ill-defined soft tissue thickening in retroareolar region with nipple retraction (arrow) and mild tracer uptake (2.3 × 1.5 cms, SUV ma × 2.2). (b) Trucut biopsy from breast showing an invasive duct carcinoma (NST) of grade 2 (H and E stain)The patient received chemotherapy and palliative whole-brain radiotherapy (in view of brain metastasis). Post 6 cycles of chemotherapy, PET-CT scan showed a partial response to treatment. Hormonal therapy was given following the completion of chemotherapy. After a follow-up period of 11 months, PET-CT scan suggested persistent disease with a new development of liver metastasis, and the patient succumbed to the disease in a month. In a study of 33 cases of metastatic carcinomas involving the cervix, 63% cases were from extragenital sites, of which four represented primary breast tumors.[3] Mazur et al.[4] studied 149 cases of metastatic tumors to female genital tract from extragenital primaries. Breast was the second most common primary site next to gastrointestinal tumors. Till date, approximately 35 cases of breast cancers metastasizing to the cervix have been reported, and only eight cases presented with metastatic cervical tumor preceding the diagnosis of the primary breast tumor.[5] In our case, the absence of brain and spine metastasis could have led to radical hysterectomy, which could have been associated with unwarranted surgical morbidity. Hence, timely and accurate diagnosis of an occult primary is imperative due to distinct therapeutic implications. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.