Painful nodule on the left fifth finger

A 75-year-old Japanese man had a history of Stage IVb squamous cell lung cancer (cT3N1M1c) with metastases to the right ribs and left adrenal gland. He had previously tested negative for key nonsmall cell lung cancer driver mutations, including epidermal growth factor receptor, anaplastic lymphoma kinase, C-ros oncogene 1, v-raf murine sarcoma viral oncogene homolog B1 and programmed cell death protein 1. He presented with a painful nodule on the distal phalanx of his left fifth finger. The nodule had gradually increased to 3 cm in diameter and had a red, vascular surface (Figure 1). Initially, the nodule was diagnosed as paronychia and treated with antibiotics, but the condition did not improve. Radiography revealed complete destruction of the distal phalanx (Figure 2), and positron emission tomography-computed tomography showed abnormal uptake in the lesion. A biopsy was performed from the lesion on the left fifth finger (Figure 3a,b).

The patient was treated with a combination of pembrolizumab and cytotoxic anticancer agents, including paclitaxel and carboplatin. After starting treatment, the acrometastasis shrank dramatically and almost disappeared within 3 months (Figure 4) and dropped off spontaneously 5 months after treatment initiation. However, the patient's condition deteriorated due to the progression of the primary lung cancer, leading to a transition to palliative care. He passed away 2 weeks later.

Acrometastases refer to secondary lesions located distal to the elbow and knee, accounting for 0.1% of all bone metastases.¹ They are often misdiagnosed due to their rarity, with 56.8% of hand or wrist lesions initially mistaken for infections such as abscess, felon, osteomyelitis, paronychia or tuberculosis.² Symptoms typically include redness, swelling, pain and limited movement. Because patients with cancer typically have the primary tumour identified first, acrometastases should be considered in the differential diagnosis of distal lesions in patients with cancer.^{3, 4} Our patient had a bone metastasis of lung cancer in the distal phalynx, which is the most common site of phalyngeal metastases.⁵ Acrometastases may occur on either the right or left hand, with bilateral metastases being relatively rare.² The primary site in our patient was situated in the middle lobe of the left lung, disseminating to the right ribs and left adrenal gland. Notably, phalangeal metastases exhibit a nonlateralized distribution pattern with no discernible association with the laterality of the primary neoplasm, regardless of whether it is in the lung, breast or kidney.

The pathophysiology of acrometastasis is not fully understood but is believed to involve the hematogenous spread of tumour emboli. Mulvey et al.⁶ speculated that venous erosion by a pulmonary neoplasm allows tumour emboli to disseminate into the left atrium and ventricle, subsequently entering systemic arterial circulation. This mechanism explains why lung cancer is the main source of digital metastases. It provides a unique pathway for tumour cells to reach the digits, unlike other visceral tumour emboli that cannot directly access the arteries to present as acrometastasis.⁷ Umana et al.⁴ reported that of 247 cases of acrometastasis, 91 (36.8%) were from lung cancer, as in this case. A notable portion (58.7%) of lung acrometastases either marked the initial detection of lung cancer or were identified concurrently with the lung cancer diagnosis, illustrating that digital metastases can be an important clue to lung cancer diagnosis. The distal phalanx is the most frequent site of acrometastasis, possibly owing to its rich blood flow and greater exposure to trauma.^{8, 9} Although our patient had no history of past trauma, unrecalled past trauma could have influenced the occurrence of metastasis in the distal phalanx. Chemotactic factors released after trauma are thought to promote cancer cell migration and adhesion, facilitating metastasis.^{9, 10}

Acrometastases are generally associated with multiorgan metastases and have a poor prognosis, with a mean survival of 7.2 months (0.5–78 months) after diagnosis.¹⁰ Treatment for acrometastasis is usually palliative, including amputation or radiotherapy.¹⁰ Of 482 cases of hand acrometastasis reported by Cattelan et al.,¹⁰ 141 were treated by amputation, 90 by radiation and 34 by chemoradiation. Amputation, although sometimes necessary, significantly reduces the patient's quality of life.

Emerging treatments, notably combination chemotherapy inclusive of immune checkpoint inhibitors—established as the standard regimen for lung cancer—have shown promise in achieving substantial regression of metastases. To our knowledge, this is the first documented case in which combination chemotherapy for lung cancer, incorporating an immune checkpoint inhibitor, led to the complete regression of acrometastasis. This finding suggests that combination chemotherapy with immune checkpoint inhibitors may provide a less invasive alternative to amputation with a less negative impact on the patient's quality of life.

Notably, the treatment was effective for the acrometastasis but not for the primary tumour. This may be attributable to differences in blood flow and genetic mutations between the primary and metastatic sites. Combination therapy with immune checkpoint inhibitors could be an effective alternative to amputation for treating acrometastases.

Chihiro Hishinuma: Writing—original draft preparation. Yuko Watanabe: Conceptualization; writing—reviewing and editing. Hideyuki Ishikawa: Supervision. Atsuhito Nakazawa: Investigation; supervision. Yukie Yamaguchi: Conceptualization; supervision.

The authors declare no conflict of interest.

The patient's family has given written informed consent for the publication of the patient's deidentified, anonymized case details (including photographs). Ethical Approval: not applicable.