Acrometastasis: The Tip of the Iceberg of Metastatic Disease from Thyroid Cancer. Two Cases Report

Abstract

Acrometastasis, especially in the hands and fingers, is a rare clinical condition resulting from primary cancers such as lung, breast, kidney, and, rarely, thyroid cancer. Acrometastasis tends to be the tip of the iceberg in patients with extensive systemic disease, which could be regional, pulmonary, skeletal, neurological, or all of them combined. Even though these tumors are clearly visible and symptomatic, the diagnosis is usually misleading because such distal metastatic disease is not thought of at first. In general, systemic treatments should be given to any patient presenting digital acrometastasis. We describe two cases of papillary thyroid carcinoma and digital acrometastasis as a sign of advanced disease.

Introduction

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. PTC, regarded as an indolent tumor, accounts for 85% of all thyroid cancers and has a 10-year survival rate of roughly 93%. Even though most PTCs are well differentiated with low rates of local invasion, recurrence, and metastasis (regional or distant), there are aggressive variants such as diffuse sclerosing, tall cell, columnar cell, solid, and hobnail variant [1]. Metastasis to soft tissues of the extremities is rare. It is even more exceptional in the hands and fingers and carries a worse prognosis.

Cutaneous metastases from solid tumors occur in 0.7 to 5.0% of cases, of which acrometastasis accounts for just 0.1%. Acrometastases usually appear at a site distant from the primary tumor and mimic other nail conditions, leading to a late or erroneous diagnosis and poor clinical management. The distal phalanx is the most common site of presentation [2]. The present report aims to describe two cases of PTC and digital acrometastasis as a sign of advanced disease.

Case 1

A 48-year-old male diagnosed with metastatic PTC to the pelvis underwent right internal hemipelvectomy. At postoperative day 10, we performed total thyroidectomy and bilateral neck dissection, whose histopathological report came back as poorly differentiated PTC. Afterward, a dose of 200 mCi of I-131 was administered. Residual tissue was found in the pelvis and presternal area, for which the patient received 60 Gy radiotherapy. A year later 150 mCi of I-131 were given, bilateral pulmonary lesions were confirmed, and a new metastatic lesion in the right thumb and subcutaneous nodules in the lumbar region were identified. We administered 20 Gy radiotherapy to the thumb and 150 mCi of I-131 with a cumulative dose of 500 mCi. At follow-up the thumb lesion had increased (Fig 1), for which palliative amputation was performed. Due to multiple metastases, palliative and symptomatic treatment were continued until his death.

Fig. 1.

A) lateral image of acrometastasis of the distal phalanx of thumb, B) inferior image, C) upper image

Case 2

A 54-year-old female diagnosed with cervical cancer in 1996, who had received platinum-based chemotherapy and 50 Gy radiotherapy, was referred to the head and neck department due to a nodule below the left thyroid lobe and level III adenopathies. Fine-needle biopsy came back as PTC. After performing total thyroidectomy and left-sided selective neck dissection, we found a 2.8 × 2 × 1.8 cm tumor and 12/29 metastatic lymph nodes. An ablative dose of 150 mCi was given. However, a new dose of 200 mCi was administered due to persistent high thyroglobulin levels. Seven years after her last ablation procedure, cervical recurrence (level VII) and a paraesophageal adenopathy were observed. She refused surgery, so we proceeded to deliver 45 Gy in 25 fractions to the mediastinum. One year after radiotherapy, an I-131 scan revealed pulmonary nodules unrelated to iodine uptake. Four years later, at follow-up, she had a convulsion which the neurosurgery unit reported as PTC metastasis. Whole brain radiotherapy (30 Gy) and steroids were administered. After 13 years of follow-up, the patient presented ecchymosis in the left second finger, and her general practitioner prescribed antibiotics, but no improvement was noted (Fig 2). A Doppler ultrasound showed no vascular disease. The distal phalanx of the left second finger was amputated, and the histopathological report came back as PTC metastasis. A month before the writing of this paper, the patient presented with a 1 cm lesion in the left jaw and swollen left nostril. PET/CT scan detected metastasis in those areas, for which she is currently undergoing radiotherapy.

Fig. 2.

A) Image of tumor in distal phalanx of the ring finger, B) radiograph of hands with metastasis in left hand ring finger, C) Tumorectomy of distal phalanx metastasis

Discussion

Extremity metastasis, especially in the hands and fingers, is a rare clinical condition resulting from primary cancers such as lung, breast, kidney, and, rarely, thyroid cancer, as in the cases we describe. This malignancy can mimic inflammatory or benign pathologies, leading to late diagnoses and inadequate treatment [3].

In 1906, reporting multiple metastatic lesions in the metacarpals of a breast cancer patient, Handley described “acrometastasis” for the first time This term refers to all metastatic lesions distal to the elbow and knee joints. In 1983 Kerin [4] published a review of 163 cases of metastatic tumors to the hands, of which 51% occurred in the distal phalanges, 29.5% in the carpal bones, and 27.6% in the metacarpals. In 2014 Afshar et al. [5] described 211 metastatic tumors to the hands and wrists mainly resulting from lung (34%), gastrointestinal tract (25%), and kidney (10%) cancer. In 1976 Uriburu et al. [6] reported the first case of acrometastasis of thyroid origin, with a 4-year disease-free period.

Only 5 cases of acrometastasis to distal phalanges due to thyroid cancer have been reported in the literature so far (Table 1) [7–11]. However, unlike other cases describing follicular carcinoma in bone metastases, our cases were associated with papillary carcinoma.

Table 1.

Reports of Acrometastasis from Thyroid cancer in the literature.

AUTHOR	CASES FOUND
Darshan Patil, Et al.	A 54-year-old female presented with swelling over the terminal part of the left little finger with thyroid cancer to the little finger along with pulmonary metastasis. Revealed metastasis from a follicular thyroid cancer (7).
Gazi Huri	An Eight-four-year-old right-hand man, who has history pf thyroidectomy in 2007, presented increasing pain and swelling at the distal part of the right thumb. In the histopathologic analysis reported metastasis from follicular cancer (8).
J. Reparaz padros, Et al.	A sixty-one-year-old woman who has a history of follicular thyroid cancer, developed pulmonary metastases 7 years after thyroidectomy and a condition in the distal phalanx of the ring finger, which she reported in her biopsy as a metastasis of thyroid cancer. (9).
Abhay K Kattepur, Et al.	A 50-year-old woman presented with a painless lesion deep in the nail of the eft little finger, were found with diffuse enlargement of the thyroid gland, with retrosternal extension and the biopsy of the thyroid revealed follicular thyroid carcinoma and the finger biopsy metastasis of the follicular neoplasm. (10).
Arvin Krishnamurthy, Et al.	A 45-year-old man with thyromegaly and a third metacarpal with tender bony prominence. Fine needle aspiration cytology from thyroid and metacarpal confirmed the diagnosis of a metastatic follicular carcinoma.11).

Even though these tumors are clearly visible and symptomatic, diagnosing them is complex because metastatic disease is not expected to be so distal. Its symptoms (e.g., edema, erythema, and pain) cause difficulties in differential diagnosis because they share common features with paronychia, fractures, tenosynovitis, gout, rheumatoid arthritis, and osteomyelitis [12].

Radiological and histopathological studies must be performed to make an accurate diagnosis, determine the extent of the disease, and assign treatment, which in general should be systemic since acrometastasis tends to be the tip of the iceberg in patients with extensive systemic disease that could be regional, pulmonary, skeletal, neurological, or all of them combined, as the 2 cases we described. Acrometastasis reflects advanced disease, patients survive on average 5.3 months after diagnosis if lesions are in the hands or 9.9 months if they are in the feet. Thus, treatments are focused on local palliation [13]. However, they must be based on histological reports and the availability of chemotherapy or immunotherapy.

Treatment options for acrometastasis of thyroid carcinoma include chemotherapy, radiotherapy, immunotherapy, and surgery. Chemotherapy and radiotherapy could be enough to reduce tumor volume and relieve pain in patients with multiple or inoperable tumors. Surgical procedures such as amputation and disarticulation are considered the best treatment for the control of metastatic disease to the distal phalanges [14]. Nowadays it is worth searching for mutations in metastatic thyroid carcinoma to improve survival, reduce tumor volume, and possibly administer I-131 in undifferentiated tumors with little or no previous uptake. BRAF V600E status and microsatellite instability should be assessed in thyroid carcinoma to expand treatment options. BRAF V600E inhibitors, such as vemurafenib or dabrafenib, are used for tumor redifferentiation to reduce tumor volume and possibly administer I-131. Moreover, despite the low prevalence of papillary carcinoma, anti-PD-1 therapy using pembrolizumab could be given. Other options include two multikinase inhibitors (i.e., lenvatinib and sorafenib) that block the activation of receptors regulating thyroid carcinoma progression [15].

Conclusion

Thyroid carcinoma acrometastasis is rare. Its occurrence is more common in follicular cancer; however, in the two cases we described it occurred in papillary carcinomas. Acrometastasis carries a poor prognosis because it is generally the tip of the iceberg of widespread metastatic disease. Despite the variety of treatment options, palliative care is the most common. Surgery can be performed to alleviate the symptoms of digital acrometastasis.