Departments of Radiation Oncology¹, Medical Oncology² and Surgical Oncology³, Valavadi Narayanasamy Cancer Center, G. Kuppuswamy Naidu Memorial Hospital, Coimbatore 641037, India.

Ga-68 labelled Prostate specific membrane antigen- Positron emission tomography (PSMA-PET) is widely used in staging of intermediate and high-risk prostate cancer or restaging after biochemical recurrence. PSMA is a type II integral membrane glycoprotein in cell surface, involved in hydrolysis of N-acetyl L-aspartyl L-glutamide into N-acetyl L-aspartate and L-glutamate. PSMA is expressed 10-80 fold in almost all cancer cells of prostate and its transmembrane location with large extracellular domain provides an accurate target for detection of extra-prostatic disease, lymph nodes and bone lesions [1-3].

       Despite the term “prostate specific”, several case reports describing the incidental uptake with Ga-68, PSMA-PET in benign and non-prostatic malignancy has been reported [4-6]. Here we present two cases of carcinoma prostate with PSMA-PET avid lesions in thyroid, requiring further evaluations due to its non-specificity and on evaluation found to be a synchronous double malignancy of prostate and thyroid.

A 72 years old male presented with complaints of lower urinary tract symptoms for 2 months duration. Serum PSA done was 15 ng/mL. MRI of pelvis showed prostate measuring 4.8×3.6×3.9 cm, volume 34 cc, diffuse T2W hypo-intensity noted in entire prostate with loss of zonal differentiation. An ill-defined early enhancing lesion noted in left side of the mid gland of prostate measuring 1.9×1.4 cm. Peri-prostatic fat planes were indistinct on the left side. No pelvic or para-aortic lymphadenopathy was seen. Histopathological examination of trans-rectal ultrasound guided biopsy of prostate revealed acinar adenocarcinoma Gleasons score of 3+4 (grade group 2) involving 13 out of 14 cores. PSMA-PET CT showed avid lesions in prostate, thyroid, enlarged pre-tracheal node and multiple pleural nodules in right lung [Fig.1].

A differential diagnosis of carcinoma prostate with metastasis or synchronous double primary in thyroid was made. Ultrasound (USG) guided biopsy of thyroid lesion and pre-tracheal node revealed follicular neoplasm. Immunohistochemistry was positive for TTF-1 and thyroglobulin and negative for PSA. He underwent thoracoscopy and biopsy of the pleural nodule in order to determine the origin. Histopathological examination showed metastatic adenocarcinomatous deposit in the pleural and lung from a primary prostatic acinar adenocarcinoma with immunohistochemistry strongly positive for PSA and negative for TTF-1. Patient underwent total thyroidectomy with central lymph node dissection and bilateral orchidectomy. Thyroid gland showed follicular variant of papillary carcinoma involving both lobes of thyroid with three nodes positive for metastasis. Post-operative Iodine-131 scan with 1.5 mCi showed minimal residual thyroid tissue in the neck. He received radioiodine ablation therapy with 30mCi of I-131 and six cycles of palliative chemotherapy with Docetaxel and Prednisolone. Post-chemotherapy PSMA-PET scan showed no evidence of disease in the body and serum PSA reduced to 0.01 ng/mL. Whole body Iodine-131 scan showed no residual disease. Patient is biochemically and clinico-radiologically disease free 18 months since completion of treatment.

A 58-year-old male evaluated for complaints of lower abdominal pain for two months duration, serum PSA done was 48 ng/ml. MRI of pelvis showed limited disease in prostate with extra-capsular extension and sub-centrimetric iliac nodes. Histopathological examination of trans-rectal ultrasound guided biopsy of prostate revealed adenocarcinoma with Gleason’s score of 7 (3+4), grade group 2. PSMA-PET CT showed avid lesions in prostate and left lobe of thyroid. USG neck done revealed 3.3×2.9×2.9 cm nodule in the left lobe of thyroid with focal extra-thyroid extension into the neck anteriorly. Fine needle aspiration cytology of the left thyroid nodule was suspicious of papillary carcinoma.

PSMA is consistently expressed in prostate cancer epithelium, enabling detection of prostate cancer with 80% sensitivity and 97% specificity on per lesion analysis and also detects relapse and metastasis with 95% sensitivity with positive predictive value of 98%. Therefore, it is used in diagnosis, staging, restaging, response to therapy and prognostication [4,5] and has paved way for radio-ligand therapy.

PSMA-PET, though has high sensitivity and specificity in staging for prostate cancer, can be taken up by multiple other malignancies and non-malignant conditions. If clinical picture warrants, additional confirmatory investigations are required, might change the staging and the treatment.

Contributors: SS: manuscript writing, patient management; ANC: manuscript editing, patient management; AR, AP: critical inputs into the manuscript. SS will act as a study guarantor. All authors approved the final version of this manuscript and are responsible for all aspects of this study.

Funding: None; Competing interests: None stated.