Abstract
Adenoid cystic carcinoma (ACC) is a malignancy affecting the salivary glands and rarely involving the lung. Due to its rarity, primary lung ACC remains incompletely understood. We herein report the case of a 57-year-old female patient who was initially diagnosed with primary lung ACC and was treated by lobectomy. Seven years later, an abdominal computed tomography scan performed in the context of surveillance revealed the presence of a solid lesion arising from the lower pole of the left kidney. The patient underwent left partial nephrectomy, and histopathology confirmed a completely excised metastatic ACC.
1. Introduction
Adenoid cystic carcinoma (ACC) is a rare form of malignancy that arises within secretory glands, most commonly the major and minor salivary glands of the head and neck. Other sites of origin include lacrimal glands, breast, skin, and vulva [1]. ACC tends to metastasize to the lung and, less frequently, to the brain, liver, and bones [2]. Primary salivary-type tumors including ACC account for approximately 0.1% to 0.2% of all lung cancers and are histologically indistinguishable from their salivary gland counterparts [2]. They originate from the submucosal glands of the tracheobronchial tree and usually behave as low-grade malignancies with better prognosis compared to conventional lung cancer. Due to its rarity, primary lung ACC remains incompletely understood, and its clinical behavior, optimal treatment, and long-term outcome have yet to be clarified.
Renal metastases have been described in other malignancies such as lung, breast, and gastric carcinoma. Metastatic involvement of the kidney is usually a feature of disseminated disease, while solitary renal metastases are less frequent and mimic primary renal tumors [3]. In patients harboring another malignancy, solitary renal masses may represent synchronous primary tumors of the kidney.
Herein, we report the case of a 57-year-old female patient who presented with a solitary renal metastasis of a lung ACC and was successfully managed by minimally invasive nephron-sparing surgery. We report this case to highlight its uniqueness in terms of primary site (lung) and natural history (metachronous solitary metastasis to the kidney), and we focus on relevant issues such as differential diagnosis, the role of organ-sparing metastectomy, and the need for long-term follow-up of this rare malignancy.
2. Case Presentation
A 57-year-old asymptomatic female patient was referred for a mm solid lesion arising from the lower pole of the left kidney, which was diagnosed by computed tomography (CT) performed in the context of annual surveillance (Figure 1). She had been diagnosed with primary lung ACC seven years earlier and underwent right lower lobectomy, without any further adjuvant treatment. On precontrast CT images, the lesion appeared well-circumscribed, homogeneous, and relatively hypodense (30 +/-5 HU). It enhanced slightly in the arterial phase (45 +/-5 HU), but the enhancement was more pronounced in the venous phase (65 +/-5 HU). On 18F-fluorodeoxyglucose positron emission tomography–CT scan (Figure 2), a lump-shaped radioactive concentration shadow was observed at the lower pole of the left kidney, with a maximum standardized uptake value of 7. No other metastatic lesions were detected. Based on imaging characteristics and the patient’s history, the differential diagnosis included nonclear cell renal cell carcinoma, renal metastasis, and benign renal tumors.
(a)
(b)
According to the Oncology Department’s protocol for small renal masses (≤4 cm in greatest dimension) of questionable origin, percutaneous CT-guided biopsy of the renal lesion was performed, and histopathological analysis revealed a pattern compatible with ACC, similar to the primary lung tumor. Given the patient’s age and the features of the tumor, nephron-sparing surgery was recommended. The patient underwent laparoscopic transperitoneal partial nephrectomy. The postoperative course was uneventful, and the patient was discharged on postoperative day two.
Gross examination of the specimen revealed a well-circumscribed, solid, and whitish tumor, measuring mm. Microscopically, tumor cells were arranged in typical cribriform, tubular, and focally solid growth patterns. Neoplastic cells were small with scant cytoplasm. The stroma manifested myxoid and hyalinized features surrounded by tumor cells forming cylindrical structures (Figure 3). Immunohistochemically, neoplastic cells showed focal cytoplasmic or very weak nuclear expression of PAX8 which was considered a negative result. The strong nuclear staining of the renal tubular epithelium was used as an internal positive control. PAX8 negativity confirmed the extrarenal and extra-Müllerian origin of the tumor. The epithelial cells showed positivity for CD117 and CK7, and the myoepithelial cells showed positivity for P63, highlighting the dual cell population of the neoplasm, a typical feature of adenoid cystic carcinoma. Surgical margins were negative. These findings confirmed a completely excised metastatic ACC. Follow-up imaging at 24 months showed no evidence of recurrent disease.
3. Discussion
Historically, metastatic involvement of the kidney was considered a rare phenomenon. According to autopsy studies, the rate of renal metastases ranges from 2.4% to 7.2% [4], while detection of renal metastases in the clinical setting is less frequent [5, 6]. The most common sites of origin for tumors that metastasize to the kidney are the lung, gastrointestinal tract, breast, ovary, soft tissue, and thyroid [5]. Most patients diagnosed with renal metastases are either asymptomatic or present with nonspecific findings, such as albuminuria or microscopic hematuria [7]. In the case presented herein, the patient was diagnosed in the context of surveillance and was completely asymptomatic.
Metastatic disease involving the kidney usually presents with bilateral and multiple lesions, associated with widespread dissemination of the primary tumor [8]. Solitary renal metastases, however, are uncommon [5], and most of these patients are diagnosed by routine imaging. Differentiation between a solitary renal metastasis and a primary renal tumor based on imaging can be challenging. Characteristics on CT scan suggestive of renal metastasis include endophytic growth, either isodensity or slightly lower attenuation compared to the normal renal parenchyma, hypovascularity ,and slight enhancement on contrast-enhanced images [3]. The imaging findings in this case are in accordance with these features.
In the past, the presence of a renal lesion in a patient with a history of extrarenal malignancy was considered an absolute indication for biopsy due to major treatment implications [5–9]. This approach, however, has been questioned in the context of solitary renal masses [5]. According to a previous retrospective study [8], decision-making in this setting can be based on the status of the extrarenal malignancy and the imaging characteristics of the renal lesion. The two major predictive factors for renal metastasis are evidence of clinical progression and/or other metastases from the nonrenal malignancy and lack of enhancement of the renal mass on imaging. The absence of progression of the nonrenal primary is considered a predictive factor for a renal primary over a solitary renal metastasis. In the case presented herein, the imaging characteristics of the lesion (endophytic, slightly low in attenuation, slight enhancement after intravenous contrast administration) were more typical of a metastatic lesion. The primary lesion, however, had been in remission, and no other metastatic focus was identified on imaging. The decision to perform percutaneous biopsy prior to surgical extirpation of the renal lesion in this case was based on the absence of progression of the primary tumor, even though the imaging findings were consistent with metastasis.
ACC is characterized by an indolent clinical course, a variable distant recurrence rate (4.1-44.7%) and a tendency for late-onset metastases [10]. The organs most frequently involved by metastatic ACC are the lungs, bones, brain, and liver [2]. On reviewing the limited cases of metastatic ACC with renal involvement, the most common primary sites are major or minor salivary glands (parotid gland, submandibular gland, palate, floor of mouth, sinonasal region), lacrimal gland, and breast [11–15]. The time interval between primary diagnosis and development of renal metastasis ranged from 3 to 14 years, with an average interval of 9.8 years, representing an indolent growth pattern and a potential for late metastases [15]. To our knowledge, only four cases of pulmonary ACC metastatic to the kidney have been described in the literature to date (Table 1) [16–19]. Two of these reports describe renal involvement in the context of widespread metastatic disease with a poor outcome [17, 18]. Surgery (with or without adjuvant radiotherapy) was the most common primary treatment modality, and the time interval between initial diagnosis of lung ACC and development of renal metastasis ranged between 3 and 23 years. All previous patients presented with symptoms indicating a renal mass (i.e., hematuria and/or flank pain), but our patient was asymptomatic and was diagnosed in the context of annual surveillance.
The prognosis of patients with distant metastases following primary lung ACC varies, but previous reports have suggested that metastases have a tendency for slow growth similar to the primary tumor [2]. In this context, complete surgical excision of metastases, if feasible, should be considered as a therapeutic option, in order to achieve control of disease and prolong survival. Given the rarity of the case presented herein, however, clear recommendations cannot be made. For metastatic ACC of the salivary glands, survival is related to the disease-free interval [20], as metastectomy for metachronous metastases () appears to achieve better disease control. While surgical excision (radical or partial nephrectomy) is considered the standard of care in patients with primary renal malignancies, there are no clear guidelines for the surgical management of renal metastases. According to the limited available data [5, 6], surgical excision of renal metastases in carefully selected patients with oligometastatic disease and good performance status achieves acceptable long-term survival rates. The role of nephron-sparing surgery in these cases is not established, since the available literature only includes case reports and nonrandomized case series. According to a large single-centre retrospective series of 151 patients, only one-third of patients were candidates for surgical excision of renal secondaries, and less than 20% of them underwent organ-sparing surgery (i.e., partial nephrectomy) [5].
Local and distant metastases of ACC are frequent due to the tumor’s tendency to invade the peri-neural space [2]. Currently, there is no consensus for the treatment of metastatic ACC, as cytotoxic chemotherapy produces very low response rates (5-15%) [21, 22]. Several advances in the understanding of the pathogenesis and molecular phenotype of this malignancy have been made, and new compounds (i.e., antiangiogenic agents, tailored agents, and checkpoint inhibitors) are under investigation. Genetic analyses have shown that MYB-NFIB fusion transcripts and/or MYB overexpression are observed in the majority of ACC cases [21]. In this context, the tyrosine kinase inhibitors axitinib, dovitinib, and lenvatinib exhibited clinical activity against ACC in phase II studies [23–25]. There remains a need for further studies that incorporate molecular analysis in the management of incurable ACC, as well as the development of effective novel therapeutic approaches.
4. Conclusion
The uniqueness of the case presented herein involves metachronous solitary metastatic renal metastasis from ACC arising at an uncommon primary site, managed by organ-sparing surgery. The patient underwent laparoscopic partial nephrectomy with negative surgical margins and remained disease-free 24 months after surgery. Since late distant metastases of ACC are not uncommon, long-term follow-up is recommended.
Data Availability
Previously reported data were used to support this study. These prior studies (and datasets) are cited at relevant places within the text as references.
Conflicts of Interest
The authors declare that there is no conflict of interest regarding the publication of this article.