BACKGROUND: Pulmonary mucoepidermoid carcinoma (PMEC) is a rare lung malignancy, especially in combination with ALK mutations, whose clinical presentation lacks specificity and for which there are no standardized treatment guidelines.
METHODS: We report a case of a patient with PMEC-predominant primary lung cancer combined with an ALK mutation.
METHODS: One patient was diagnosed with PMEC combined with ALK mutation.
METHODS: After diagnosis by puncture pathology, the patient was treated with oral targeted drugs.
RESULTS: The patient\'s cough and fever were controlled, her diet improved significantly, and she gained 20 pounds in 6 months. During this period, the primary and metastatic foci in the lungs were significantly reduced on repeat chest CT.
CONCLUSIONS: PMEC combined with ALK mutation is an extremely rare primary lung cancer, and the diagnosis is mainly based on pathology, histology and immunohistochemistry. The application of molecularly targeted drugs to patients with mutations can significantly improve the prognosis of patients with PMEC, which is expected to be a new breakthrough in the treatment of PMEC.

BACKGROUND: Distant metastases from lung cancer are commonly found in the brain, bone, and liver. Metastases to the breast from non-mammary malignancies are extremely rare, and their clinical presentations remain unclear.
METHODS: We herein report a case of bilateral breast metastases from anaplastic lymphoma kinase-positive advanced lung cancer in a 51-year-old Japanese male patient. During the course of systemic treatment for advanced lung cancer, computed tomography revealed bilateral breast enlargement without contrast enhancement, a finding consistent with gynecomastia. While other metastatic lesions responded to chemotherapy, both breast masses grew vertically like nodules. The breast masses were immunohistochemically diagnosed as metastases from lung cancer and were removed surgically. Simultaneous bilateral breast metastases from malignancies of other organs, like ones in this case, have rarely been described.
CONCLUSIONS: It is important to keep in mind that breast metastases from nonmammary malignancies are a possible explanation for unusual breast findings in a patient with a history of malignancies.

A 57-year-old male underwent an open right radical nephrectomy in 2015 for a 3-cm kidney tumor which was classified at the time as a combined tubulocystic and collecting duct carcinoma. One of six nodes was positive for metastatic carcinoma and the patient received adjuvant carboplatin/gemcitabine chemotherapy. In 2020, he developed enlarging retroperitoneal adenopathy and underwent a retroperitoneal lymph node dissection with 11 of 13 nodes in the resected specimen positive for the previously described renal carcinoma, followed by adjuvant radiotherapy. In November 2022, he again underwent surgery for further locoregional recurrence with resection of a right psoas mass lesion and right hemicolectomy. Pathology on this occasion was reclassified as anaplastic lymphoma kinase-rearranged renal cell carcinoma (ALK-RCC). Shortly afterward, a restaging CT revealed multiple liver metastases and evidence of further disease recurrence in the right renal bed. He commenced alectinib with a complete radiological response and has continued on it for 12 months at the time of writing this report. To our knowledge, there are only five prior reports of ALK-RCC treated with targeted ALK inhibitor therapy in the literature. We report this case to highlight the importance of recognizing and diagnosing this rare RCC subtype since it has significant therapeutic implications. Furthermore, to our knowledge, this patient has had the longest follow-up reported to date in the literature so far. A concerted effort by the histopathology and oncology community is needed to gather more data on the incidence and treatment outcomes of these tumors so that progress can be made in optimizing their management. It is important to consider novel and emerging entities from the most recent WHO 2022 classification, many of which are defined by molecular characteristics with associated therapeutic implications.

Anaplastic lymphoma kinase (ALK) is detected in both normal and oncological developmental tissues. Among ALK-related tumors, superficial ALK-rearranged myxoid spindle cell neoplasm (SAMS) is a rare, soft tissue tumor characterized by the immunophenotypical co-expression of CD34 and S100. Here, we describe a patient with this rare tumor and outline its clinical and radiological characteristics. A 28-year-old woman with diabetes, hypertension, and panic disorder presented with discomfort caused by a rubbery mass on the left buttock that had persisted for 10 years. Computed tomography revealed a multilobulated hypodense mass with small internal enhancing foci, posing challenges for the exact diagnosis of the lesion. The entire lesion was excised with clear resection margins. An 8.0 × 6.0 cm, well-circumscribed tumor with a lobular growth pattern was observed in the deep subcutaneous tissue. Light microscopy revealed epithelioid, ovoid, and spindle-shaped cells with a reticular cordlike pattern. Immunohistochemistry results were positive for S100, CD34, and vimentin. Break-apart fluorescence in situ hybridization assay results for ALK were also positive. These findings were consistent with those of SAMS. This case suggests that SAMS should be considered when identifying large nonspecific masses during clinical and imaging evaluation.

Multiple primary lung cancer (MPLC) refers to patients with two or more primary lesions of lung cancer. It can be divided into synchronous MPLC (sMPLC) and metachronous MPLC (mMPLC) based on the timing of occurrence. In recent years, the detection rate of MPLC has gradually increased. However, considerable controversy exists in distinguishing MPLC from intrapulmonary metastasis (IM), especially when the histopathological types are identical. Given the significant differences in treatment strategies and prognosis in clinical practice currently, accurate diagnosis of MPLC is crucial for personalized precision therapy. Molecular genetics and sequencing technologies offer effective strategies for assessing the clonal origin of tumors. There have been reports of coexisting mutations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) fusion genes in non-small cell lung cancer, but case of EGFR mutation following an ALK mutation has not been mentioned. This article accurately diagnoses and retrospectively analyzes the clinical data of a case of ALK mutant adenocarcinoma in a male patient who developed an EGFR mutation with multiple metastases four years after surgery, and reviews the relevant literature. This paper aims to deepen the understanding of mMPLC and provide clinical references for the diagnosis and treatment of such patients.
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【中文题目：EGFR和ALK基因异时性突变非小细胞肺癌
1例报告并文献复习】 【中文摘要：多原发肺癌（multiple primary lung cancer, MPLC）指患者有两个或两个以上原发病灶的肺癌，根据发生时间的不同分为同时性多原发肺癌（synchronous MPLC, sMPLC）和异时性多原发肺癌（metachronous MPLC, mMPLC）。近年来，MPLC的检出率逐渐升高，但由于肿瘤的异质性，在鉴别MPLC和肺内转移（intrapulmonary metastasis, IM）上存在许多争议，特别是病理组织学类型相同时。考虑到目前二者在临床治疗策略及预后上的显著差异，对于MPLC和IM的精确诊断是个体化精准治疗的关键。分子遗传学及测序技术为检测肿瘤的克隆性起源提供了有效的策略，其中非小细胞肺癌表皮生长因子受体（epidermal growth factor receptor, EGFR）突变与间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）融合突变共存的病例陆续有报道，但ALK基因突变后再发EGFR突变的案例未见提及。本文通过分子遗传学技术准确诊断并回顾性分析了1例ALK突变型男性肺腺癌患者术后4年再发EGFR突变合并多发转移的临床资料，并复习相关文献，以期加深对mMPLC的认识，为该类病例的诊疗提供临床借鉴。
】 【中文关键词：异时性多原发肺癌；肺内转移；EGFR；ALK】.

Lung cancer is the malignant tumor with the highest incidence and mortality rate worldwide. For lung adenocarcinoma, identifying specific gene mutations, fusions, and giving corresponding targeted drugs can greatly improve the survival time of the patients. Among them, anaplastic lymphoma kinase (ALK) fusion occurs in 3%-7% of non-small cell lung cancer (NSCLC). In clinical practice, a variety of detection methods can be used to determine the ALK fusion status, but false negative test results are possible. This paper retrospectively analyzed the diagnosis and treatment of a patient with lung adenocarcinoma, judged the ALK fusion status by various detection methods. Among them, immunohistochemistry (IHC)(Ventana D5F3), RNA based next-generation sequencing (RNA-based NGS) confirmed positive echinoderm microtubule associated protein like 4 (EML4)-ALK fusion, while DNA-based NGS was negative. This paper analyzed the detection methods of ALK fusion, in order to clarify which detection method is the most accurate and simple to choose in different clinical cases and guide the subsequent treatment.
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【中文题目：RNA-based NGS检测EML4-ALK融合
V1亚型肺腺癌1例】 【中文摘要：肺癌是全球发病率和死亡率最高的恶性肿瘤。对于肺腺癌而言，识别特定的基因突变并给予相应靶向药物可大大提高患者的生存时间。其中，间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）融合发生在3%-7%的非小细胞肺癌（non-small cell lung cancer, NSCLC）中。在临床中，多种检测方法可应用于判断ALK融合状态，但存在检测结果假阴性可能。本文回顾性分析1例肺腺癌患者的诊治经过，经多种检测方式判断ALK融合状态，其中，免疫组化（immunohistochemistry, IHC）（Ventana D5F3）、基于RNA的下一代测序（RNA-based next-generation sequencing, RNA-based NGS）检测证实棘皮类微管关联蛋白样4（echinoderm microtubule associated protein like 4, EML4）-ALK融合阳性，而基于DNA的NGS（DNA-based NGS）检测为阴性。本文比较分析判断ALK融合的检测方法，以明确在不同临床案例中选择何种检测方式最准确、最简便，以便于指导后续治疗。
】 【中文关键词：肺肿瘤；间变性淋巴瘤激酶；基因融合；下一代测序；免疫组化；靶向治疗】.

Patients with anaplastic lymphoma kinase (ALK) fusion lung adenocarcinoma may develop drug resistance after treatment with ALK-tyrosine kinase inhibitor (ALK-TKI), and the mechanisms of this resistance are not yet fully defined. The Affiliated Hospital of Zunyi Medical University admitted a patient who was resistant to ALK fusion after ALK-TKI treatment, leading to disease progression and subsequent biopsy indicating a transformation to small cell lung cancer in September 2021. The patient, a 54-year-old female, initially presented with symptoms of cough, sputum production, and chest pain for 4 months. Chest CT showed a neoplastic lesion in the posterior segment of the right upper lobe to right lower lobe with obstructive pneumonia, metastasis in the right lower lobe, increased and enlarged mediastinal and right hilar lymph nodes, and thickening of the right hilar soft tissue. Bronchoscopy and pathological biopsy confirmed the diagnosis of lung adenocarcinoma. The results of next-generation sequencing indicated that echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion is associated with tumor protein 53 (TP53) and retinoblastoma 1 (RB1) gene mutations. The patient received second-generation ALK-TKI aletinib, achieving a progression-free survival of 11 months before disease progression suggested aletinib resistance. Subsequently, the third-generation ALK-TKI lorlatinib administered for one month without efficacy, resulting in rapid systemic disease progression. The neuron specific enolase (NSE) was significantly increased, and the patient developed new pleural, pericardial, intracranial, liver, and multiple bone metastases occurred in a short period. A second biopsy indicated small cell lung cancer. Modification of treatment regimen to chemotherapy combined with immunotherapy proved effective. The mechanisms of drug resistance of ALK-TKI treatment for advanced non-small cell lung cancer with ALK fusion are complex, and small cell transformation of pathological type is one such mechanism, although rare. Concurrent TP53 and RB1 gene mutations may be characteristic of this transformation. Elevated NSE can serve as a predictive serum marker for adenocarcinoma transforming to small cell carcinoma. Timely re-biopsy and selection of subsequent treatments based on different resistance mechanisms are crucial for comprehensive disease management.
间变淋巴瘤激酶(anaplastic lymphoma kinase，ALK)融合的肺腺癌患者经ALK-酪氨酸激酶抑制剂(ALK-tyrosine kinase inhibitor，ALK-TKI)治疗后可能会产生耐药，其耐药机制尚未完全明确。遵义医科大学附属医院2021年9月收治1例ALK融合的肺腺癌患者，经ALK-TKI治疗后出现耐药，疾病进展后再次活体组织检查(以下简称“活检”)，病理类型转化为小细胞肺癌。该患者为54岁女性，首诊主要症状为咳嗽、咳痰、胸痛4个月。胸部CT检查见右上叶后段-右下叶肿瘤性病变并阻塞性肺炎，右肺下叶转移瘤，纵隔、右肺门淋巴结增多、增大，右肺门软组织增厚；支气管镜检查病理活检明确诊断肺腺癌；二代测序基因检测结果提示棘皮动物微管样蛋白4-间变淋巴瘤激酶(echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase，EML4-ALK)融合伴随肿瘤蛋白53(tumor protein 53，TP53)和视网膜母细胞瘤1(retinoblastoma 1，RB1)基因突变。给予二代ALK-TKI阿来替尼靶向治疗，无进展生存期11个月。随后出现疾病进展，考虑对阿来替尼耐药，改为三代ALK-TKI洛拉替尼靶向治疗1个月无效，疾病快速系统性进展，神经元特异性烯醇化酶(neuron specific enolase，NSE)明显升高，短期内新发胸膜、心包、颅内、肝脏、骨转移。二次活检的结果提示为小细胞肺癌，更改治疗方案为化学治疗联合免疫治疗，症状缓解。ALK-TKI治疗ALK融合的晚期非小细胞肺癌耐药机制复杂，病理类型小细胞转化也是耐药机制之一，发生率极低，伴随TP53和RB1基因突变可能是其向小细胞转化的特征，NSE异常升高是腺癌向小细胞转化有预测作用的血清标志物，耐药后及时进行二次活检，根据不同耐药机制选择后续治疗对疾病全程管理非常重要。.

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ALK-rearranged RCC refractory to several lines of treatment has a durable response when treated with alectinib.

间变性淋巴瘤激酶（ALK）重排的肾细胞癌是第5版WHO肾肿瘤分类中新定义的一种与分子改变相关的肾细胞癌。ALK基因有多种融合伴侣。本文报道了1例罕见的伴肺转移的STRN：：ALK基因融合的肾细胞癌，根据其典型的病理组织学形态、免疫组织化学特征和分子遗传学改变明确诊断。.