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Introduction

Adenoid cystic carcinoma (ACC) is a rare malignant tumour predominantly originating in the salivary glands, accounting for ~10% of salivary gland tumours and 1% of head and neck cancers (1). However, it can also occur in other anatomical locations, including the lungs, trachea, breast, uterus, prostate and skin. Of note, studies have indicated that nonsalivary gland primary ACC accounts for approximately half of all ACC cases (2), whereas intraosseous ACC (IACC) comprises <0.4% of all ACC cases (3). ACC can present at any age, but it is most frequently diagnosed in individuals aged 40 to 60 years, with a slight female predominance, and it lacks specific clinical signs or symptoms (4). Characterized as a slow-growing, invasive tumour, ACC often infiltrates peripheral nerves, leading to local recurrence or distant metastasis, most commonly affecting the lung, followed by the bones, liver, brain and other organs. The overall survival rate for patients with ACC ranges from 68 to 90% (5), but this rate decreases to 52 and 28% at 10 and 15 years, respectively. Diagnostic procedures for ACC include imaging tests such as ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Fine-needle aspiration histopathological examination offers superior diagnostic accuracy. The primary treatment strategy involves surgical excision of the tumour, supplemented by postoperative radiotherapy and chemotherapy (6). As ACC is frequently detected at an advanced stage due to its slow course, preoperative diagnosis plays a crucial role. This case report aims to increase awareness of this uncommon disease.

Case report

A 47-year-old man presented with recurrent right-sided chest pain persisting for more than two weeks presented to Affiliated Hospital of Zunyi Medical University (Zunyi, China) in May 2023, without any cough, fever or dyspnoea. The patient had a past medical history of coronary artery disease and coronary angiography revealed 60–70% stenosis of the right coronary artery. Over the past year, the patient had experienced recurrent chest pain, with notable exacerbation of right-sided chest pain in the preceding two weeks. The patient had no history of surgery, trauma or familial predisposition. Physical examination did not reveal any significant cardiopulmonary abnormalities.

Thoracic CT imaging revealed a soft-tissue mass in the right anterior chest wall, ~5.7×4.2×5.4 cm in size, which bulged out towards the thoracic cavity (Fig. 1A). The tumour exhibited marked uneven enhancement (Fig. 1B) and encased the anterior segment of the fourth rib on the right side, with areas of osteolytic bone destruction, but no calcification was observed (Fig. 1C). There was no evidence of intrapulmonary infiltrates or enlarged lymph nodes in the mediastinum or axilla (Fig. 1D and E). Based on these findings, the CT suggested a diagnosis of a malignant tumour. Common malignant tumours arising in the ribs include chondrosarcoma, osteosarcoma, Ewing sarcomas and plasmacytoma (7). All of these tumours can manifest as osteolytic bone destruction with soft tissue mass formation, which is difficult to distinguish on imaging. Certainly, the possible presence of metastasis needs to be identified. Whole-body bone scintigraphy revealed an increased uptake in the right 4th rib (Fig. 1F). Therefore, the patient underwent a CT of the chest and whole abdomen and an MRI of the head, which did not reveal any significant metastases (Fig. 2). Considering the high likelihood of the tumour being malignant and the absence of obvious metastases, direct surgical excision of the mass was recommended for a definitive diagnosis without a prior biopsy.

Figure 1. (A) Chest CT image showing a soft tissue density mass in the right chest wall (arrow). (B) Enhanced CT shows the mass exhibiting significant uneven enhancement. (C) The CT bone window shows the mass attached to the chest wall by a wide base, with osteolytic bone destruction in the right 4th rib (arrow). (D) The chest CT lung window revealed no lung infiltration by the tumour. (E) Coronal CT image showing that the soft tissue mass encircled the right 4th rib (arrow). (F) Whole-body bone scintigraphy 3 h after intravenous injection of 99mTc-MDP revealed that the right 4th rib presented as a shadow of abnormal radiation accumulation (arrow).

Figure 2. Head and neck MRI image showing no significant parotid tumours; (A) transverse, (B) left sagittal and (C) right sagittal images.

After surgical contraindications were excluded, the patient underwent surgery to remove the mass. An incision ~15 cm in length was made in the 5th intercostal space of the right anterior chest wall, with layer-by-layer dissection through the skin and muscle to expose the fourth rib. A cauliflower-like tumour, ~2×4 cm in size, was observed on the surface of the right 4th rib, growing outwards with an intact envelope, with the inferior edge of the tumour affecting the 5th rib. The side of the tumour adjacent to the chest cavity was smooth with no lung invasion. The intercostal muscle and thickened soft tissue from the lower edge of the 4th rib and the upper edge of the 6th rib were taken as the upper and lower incision margins, respectively. The left incision margin followed the fourth rib proximal to the right side of the sternum and the right incision margin extended 3 cm distal to the fourth rib. The tumour was completely excised and the right chest wall was reconstructed. Postoperative histopathological examination (8) of different parts of the tumour revealed tumour cells arranged in sheets and nests surrounded by ductal and myoepithelial cells, and skeletal muscle infiltration was observed (Fig. 3A and B). All surgical margins were pathologically negative. Immunohistochemical testing (9) revealed the following findings: Cytokeratin (CK) (++++), vimentin (+++), CK7 (++), CK5/6 (positive), tumor protein 63 (P63) (++), S-100 proteins (S-100) (++), smooth muscle actin (SMA) (++), epithelial membrane antigen (++) and Ki-67 ~50% + (Fig. 3C) (cat. nos. RAB-0050, MAB-0735, MAB-0820, MAB-0744, MAB-0694, Kit-0007, MAB-0890, Kit-0011 and MAB-0672, respectively; Fuzhou Maixin Biotech). The final pathological diagnosis was solid-type adenoid cystic carcinoma, grade III.

Figure 3. Pathological microscopic observations revealed that (A) the tumour cells were uniform in size and arranged in sheets and nests, and (B) a high-magnification image of a different part of the tumour revealed that tumor cells were closely arranged, had a small size and deeply stained nuclei, and mitotic figures were observed [haematoxylin and eosin; scale bars, 100 µm; magnification, (A) ×100 and (B) ×200]. (C) Immunohistochemical staining of the tumour revealed P63++ (scale bar, 100 µm).

The patient was advised to undergo fluorescence in situ hybridization (FISH) or next-generation sequencing tests to identify potential genetic mutations, as well as postoperative chemotherapy or radiotherapy. However, the patient declined these and opted for regular follow-up. Half a month after discharge, the patient suddenly experienced dyspnoea and noticed blood oozing from the surgical incision. Emergency investigations revealed a heart rate of 149 beats/min (reference range, 60–90 beats/min), a blood pressure of 90/60 mmHg (reference range, 90–140/60–90 mmHg) and a haemoglobin level of 78 g/l (reference range, 120–160 g/l). A chest CT revealed right-sided haemopneumothorax with pulmonary atelectasis (Fig. 4A). An immediate emergency thoracotomy was performed to explore and control the bleeding. The patient's vital signs were stable 5 days after the operation and a repeat chest CT revealed a significant reduction in pneumothorax (Fig. 4B); the patient was subsequently discharged. During this period, the patient was again advised to undergo chemotherapy or radiotherapy, but the patient continued to refuse. At 16 months post-surgery, a chest CT revealed pleural and intrapulmonary metastasis (Fig. 4C). The patient was transferred to a separate hospital for chemotherapy consisting of paclitaxel at 330 mg and carboplatin at 600 mg every three weeks. The patient remains under monthly follow-up.

Figure 4. (A) Chest CT 12 days after tumour resection showing right-sided haemopneumothorax with pulmonary atelectasis, and (B) chest CT after the removal of haemopneumothorax. (C) CT of the chest 16 months after tumour resection revealed multiple pleural and intrapulmonary metastases (arrows).

Discussion

ACC is a tumour predominantly arising in the salivary glands, with a relatively high incidence in the submandibular glands, minor salivary glands and mucous glands of the sinuses and oropharynx (1). Although ACC can manifest in other locations, its occurrence in bones is exceedingly rare, with few documented cases in the maxilla and mandible (10,11). The following diagnostic criteria have been established for primary IACCs: i) Definite radiographic evidence of osteolysis, ii) intact cortical plates, iii) an intact mucous membrane overlying the lesion, iv) no definite primary tumour in the salivary glands, and v) histological confirmation of ACC (12). In the patient of the present study, the tumour was located in the right 4th rib and a CT revealed significant osteolytic bone destruction. Whole-body bone scintigraphy also revealed a rib tumour. Surgery and postoperative histology confirmed that the tumour arose from the ribs and immunohistochemistry verified the diagnosis of ACC. These findings satisfied the diagnostic criteria for primary IACCs. The pathogenesis of IACC is not clear, though certain scholars suggest that primary ACC in the mandible may originate from the ectopic entry of adjacent salivary gland tissue into the lingual cortex during embryonic development. Another theory posits that the tumours originate from the metaplasia and malignant transformation of epithelial cells (13). In the present case, the tumour was located far from any salivary gland and it was hypothesized that it originated from the malignant transformation of epithelial cells.

ACC occurring in bone typically presents with worm-like bone destruction, with an intact, thin or perforated bone cortex and the formation of soft-tissue-density masses on CT, which can be mildly enhanced. Osteosclerosis is less common (3,14,15). Differentiating IACCs from other malignant bone tumours on imaging is challenging; thus, pathology is the gold standard for diagnosis. Histologically, ACC exhibits biphasic differentiation of ductal and myoepithelial cells, with three primary growth patterns: Cribriform, tubular and solid, with cribriform being the most prevalent. The ACC grade correlates with its growth pattern: Grade I ACC has predominantly tubular growth, Grade II ACC is cribriform and Grade III ACC has a solid component exceeding 30% (16). Owing to their biphasic differentiation, ductal epithelial cells frequently express CK7 and CD117, while myoepithelial cells express S-100, P63, SMA and calponin (3). In terms of molecular pathology, ACC frequently exhibits a t(6;9) translocation, producing a v-myb avian myelobastosis viral oncogene homolog (MYB):nuclear factor I/B gene fusion and leading to the overexpression of the MYB oncoprotein (17). MYB oncoprotein detection is also used to confirm the diagnosis of ACC. NOTCH1 mutations have been detected in recurrent/metastatic ACC and are associated with a poor prognosis (18). These findings also indicate that the NOTCH1 and MYB genes are promising therapeutic targets.

The differential diagnosis for the patient of the present study included the following: i) Chondrosarcoma, the most common malignant rib tumour characterized by worm-like bone destruction with soft tissue mass formation and stromal calcification. Pathologically, chondrosarcomas exhibit neoplastic chondrocytes and cartilage stroma, which are often calcified. Immunohistochemistry has shown no specificity, S-100 is positive and IDH1 and IDH2 mutations are present in certain tumours (19). ii) Solitary plasmacytoma: On CT, there is commonly well-circumscribed chisel-like bone destruction, soft tissue masses and obvious destruction and interruption of the bone cortex; at times, a ‘soap bubble’ appearance can be observed. Histologically, it shows clonal plasma cell proliferation without bone marrow spread and immunoglobulin levels are generally normal (20). iii) Ewing's sarcoma: Primarily affecting patients <20 years of age. The typical imaging findings are osteolytic bone destruction with a soft tissue mass and a characteristic ‘onion skin’ periosteal reaction. Histologically, Ewing's sarcoma typically features closely arranged small round cell tumours, and immunohistochemical characteristics include strong and diffuse positive expression of CD99 (21). The main points of differentiation are summarized in Table I (19–21).

Table I. Differential diagnoses of primary rib intraosseous adenoid cystic carcinoma.

Table I.

Differential diagnoses of primary rib intraosseous adenoid cystic carcinoma.

Pathology	Age group/clinical feature	Imaging findings	Pathological feature
Chondrosarcoma	40–60 years old; distant metastasis is rare; mostly occurring at the costochondral junction	Stromal calcification	Neoplastic chondrocytes and cartilage stroma; S-100 positive
Solitary plasmacytoma	40–50 years old; plasma cells proliferate abnormally	‘Soap bubble’ appearance	Clonal plasma cell
Ewing sarcomas	Individuals under 30 years of age; early metastasis and easy to relapse	‘Onion skin’ periosteal reaction	Small round cells; CD99 strongly positive

Although ACC is a slow-growing tumour, it remains invasive and is characterized by frequent perineural invasion. Current evidence-based guidelines recommend radical surgery with postoperative radiotherapy (PORT). The principle of surgery is to excise the lesion to a negative margin (5). The extent of neural infiltration can be assessed preoperatively via MRI to plan a surgical procedure. The degree of lymph node clearance can be determined by the surgeon based on the patient's condition. ACC occurring in the head and neck region poses surgical challenges due to complex anatomy; at this point, ensuring that the surgical margins are negative is difficult. One study suggested that neural infiltration and positive cut margins do not affect survival in patients with neural infiltration who are receiving PORT (22). The typical PORT prescription dose is 54–71 Gy, with a median of 64 Gy (23). Indications for PORT include a large primary tumour, nerve invasion, positive margins, or if the surgeon considers the primary tumour unresectable (24). Multiple studies have demonstrated that surgery combined with radiotherapy improves the 5-year local control rate compared with surgery alone. However, certain studies indicate that PORT can only play a role in local control and has no effect on disease-free or overall survival. This effect was more pronounced in intermediate- and high-risk patients and was not significant in low-risk patients (24,25). The toxicity and cost of treatment also need to be considered.

Systemic therapy is primarily used for ACC where metastasis and recurrence have occurred and can be considered when surgery and radiotherapy are not possible (5). There is no standard medication regimen, though common regimens include platinum-based single-agent or combination therapies, and objective response rates are higher for combination programs. These drugs include cisplatin/vinorelbine, cisplatin/doxorubicin/cyclophosphamide, carboplatin/paclitaxel and gemcitabine/carboplatin (26). However, combination regimens may limit the use of multiple drugs because of their toxicity and side effects, such as nephrotoxicity, peripheral neuropathy, vomiting, myelosuppression and hearing loss (27).

The prognosis of patients with ACC, an indolent malignant tumour, is influenced by various factors. Positive surgical margins, nerve infiltration and solid growth patterns are associated with poor outcomes (28). Studies have also identified receptor tyrosine kinase c-KITT (CD117), VEGF and lymphovascular invasion as poor prognostic markers (23,29). In addition, the site of tumour origin and metastasis also has an impact on prognosis. ACC in major salivary glands has a better prognosis, whereas ACC in the nasal sinus area has a worse prognosis (22). Patients with lung-only metastases have a better prognosis than those with bone-only metastases (30). The patient of the present study developed pleural and intrapulmonary metastases, but the patient did not receive PORT and the specific prognosis needs to be followed up continuously.

The present case is the first case of primary ACC of the rib reported to date, and there are several limitations: The patient was not tested for MYB and was not subjected to FISH analysis, and despite a negative surgical margin, the patient did not receive any postoperative radiotherapy, and lung and pleural metastases were discovered 16 months after surgery.

In conclusion, the current study presented a rare case of ACC of the rib, combined with its CT, bone imaging and histopathological findings, and it was indicated to be a solid grade III ACC with a primary origin in the rib. This previously unreported site for ACC enhances the current understanding of the disease.

Acknowledgements

Not applicable.

Funding

This work was supported by the Science and Technology Program of Guizhou, China (grant Guizhou Science and Technology Cooperation Support [2021] general no. 432).

Availability of data and materials

The data generated in the present study may be requested from the corresponding author.

Authors' contributions

SLi: Literature search and manuscript writing. BL: Examined the patient. SLu: Pathological review. RF and SLi: Obtained and analyzed patient data and performed the patient follow-up. KJ: Conception and critical review. SLi and BL confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.

Ethics approval and consent to participate

Ethics approval was provided by the Biomedical Research Ethics Committee of the Affiliated Hospital of Zunyi Medical University (Zunyi, China; approval no. KLLY-2023-042).

Patient consent for publication

The patient provided written informed consent for the case study to be published, including case information and images.

Competing interests

The authors declare that they have no competing interests.

References