Synchronous Metastatic Follicular Carcinoma and BRAF Mutated Papillary Carcinoma Thyroid—a Rare Occurrence

Case Report

A 71-year-old female presented with complaints of pain and swelling over the left temporal region of 3 months’ duration. MRI of the orbits showed lobulated altered signal intense mass lesion in the left infratemporal region causing destruction of squamous part of the left temporal bone, greater wing of the sphenoid, and lateral wall of the left orbit measuring 46 × 34 × 39 mm. The mass was extending into the middle cranial fossa compressing the temporal lobe and extending into the intraconal space of left orbit displacing the lateral rectus and optic nerve laterally suggestive of metastatic deposit. Fine needle aspiration cytology from the same showed metastatic deposits of papillary thyroid carcinoma. Contrast-enhanced CT neck showed evidence of heterogeneously enhancing hyperdense soft-tissue mass involving the left anterior temporal region, extending into left orbit, left infratemporal fossa, soft tissues of adjacent scalp causing destruction of the left fronto-temporal bone, greater wing of sphenoid, and left lateral wall of orbit measuring about 44 × 38 × 34 mm. Multiple hypodense nodules were seen in both lobes of thyroid gland with left lobe nodules showing rim calcification, suggestive of carcinoma thyroid. Tc 99 m–MDP bone scan confirmed metastases at only the left temporal region and excluded any additional metastatic foci. Total thyroidectomy was done and sent for histopathology examination. Grossly left lobe showed a lesion measuring 1.2 × 1.2 × 1 cm and a separate nodule measuring 0.5 × 0.5 × 0.2 cm seen 1 cm away from this lesion. Microscopy favored synchronous (mixed) follicular carcinoma which showed capsular invasion (minimally invasive) and papillary carcinoma thyroid (encapsulated classic papillary microcarcinoma) involving the left lobe of thyroid with the two tumors separated by normal thyroid parenchyma. Immunohistochemistry by BRAF V600E was positive in papillary thyroid carcinoma and negative in follicular thyroid carcinoma (Fig. 1). Isthmus and right lobe of thyroid were unremarkable. Patient was given adjuvant radioactive iodine (RAI) therapy. The 36-week follow-up of this patient is uneventful.

Fig. 1.

A MRI of the orbits showing lobulated altered signal intense mass lesion in the left infratemporal causing destruction of squamous part of the left temporal bone, greater wing of the sphenoid, and lateral wall of the left orbit measuring 46 × 34 × 39 mm. B H&E 40 × showing FTC and PTC foci; C H&E 100 × showing PTC, classic subtype focus; D H&E, 100 × showing FTC focus; E IHC-BRAF in PTC focus: positive; F IHC-BRAF in FTC focus: negative. MRI, magnetic resonance imaging; PTC, papillary thyroid carcinoma; FTC, follicular thyroid carcinoma; IHC, immunohistochemistry

Discussion

Incidence of thyroid malignancies has been gradually declining in both men and women at a combined pace of 2.5% per year with an estimate of 43,800 cases per year [1]. Differentiated thyroid cancers constitute 80% of thyroid malignancies that originate from the thyroglobulin-secreting follicular cells with papillary and follicular carcinomas being the most common type [2].

Gluckmann classified second malignancies occurring in the same individual as synchronous if they occurred simultaneously or within a 6-month period of diagnosis of the first tumor and metachronous if diagnosed beyond 6-month interval [3]. Synchronous thyroid tumors are rare and present a diagnostic and treatment challenge. Synchronous tumors are classified into collision tumors, mixed tumors, and composite tumors. Synchronous mixed tumors have a common cellular origin and are separated by normal tissue between the two tumors [6]. Synchronous occurrence of medullary thyroid carcinoma (MTC) and PTC are reported in the literature [4]. Synchronous occurrence of papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) is rare [5]. PTC tends to disseminate through lymphatic spread to lymph nodes and FTC tends to disseminate hematogenously to lung, bone, and central nervous system rarely [6]. Hence, synchronous presentation has potential risk for both lymphatic and hematogenous metastasis and so the presence of two primary cancers has an aggressive behavior with increased risk of recurrence [7].

Classic PTC and subtypes showing papillary architecture harbor BRAF p.V600E in contrast to RAS mutations and the rare BRAF p.K601E in follicular patterned tumors [8]. PTC with co-existent mutations in BRAF p.V600E and TERT-promoter are associated with worse disease-specific survival. Testing for these molecular markers is not currently recommended for prognostication and management of PTC. However, they can provide valuable targets for those PTC refractory to conventional treatment protocols [11].

Treatment guidelines are poorly defined due to the paucity of reported literature. Management of these tumors is challenging, as they usually contain components with different aggressiveness, treatments options, and prognosis. The management needs to be individualized considering biological aggressiveness and the stage of the tumor. Some authors recommend that each component should be treated as a separate synchronous primary [9] while others suggest that the most aggressive of the neoplasms should dictate the treatment, usually including surgical resection and adjuvant therapy [10]. Adjuvant RAI treatment is recommended for differentiated thyroid cancers with high-risk clinical factors (such as the extent of the primary tumor, histology, degree of lymphatic invasion, lymph node metastases, postoperative thyroglobulin, and age at diagnosis) which predicts a significant risk of recurrence, distant metastases, or disease-specific mortality [5, 11]. Documenting of these rare combinations and maintaining follow-up data on these patients will help in better understanding of pathogenesis and molecular underpinning which will impact the prognosis, treatment, and potential for recurrence. Hence, we document this case owing to its rarity [12].

Conclusion

As there is absence of literature and data on long-term follow-up, specific treatment guidelines and prognosis of this entity are still unknown. Standardized diagnostic and treatment protocols will be evolved with greater reporting and follow-up of such patients.

Declarations

Conflict of Interest

The authors declare no competing interests.