BackgroundIsolated pulmonary light-chain deposition disease (LCDD) is a rare presentation of monoclonal immunoglobulin deposition disease and is histologically characterized as Congo red-negative amorphous tissue deposits in the lung.PresentationA 73-year-old woman with a history of IgG-kappa chronic lymphocytic leukemia (CLL), not requiring therapeutic management, presented with unintentional weight loss, night sweats, and flushing. Positron emission tomography/computed tomography (PET/CT) scan showed a 1-cm fluorodeoxyglucose (FDG)-avid nodule in the right lower lobe of the lung. She underwent wedge resection, which showed a lymphoplasmacytic infiltrate with associated deposits of dense eosinophilic material that mass spectrometry revealed to consist of kappa immunoglobulin light chains. Flow cytometry and IGH clonality analysis detected a small kappa-restricted lymphocytic population with only a few minor clones overlapping with the patient's CLL-associated clone, indicating minimal involvement of CLL and possible other etiologies of immunoglobulin overproduction and tissue deposition.DiscussionThis case report highlights the importance of accurate diagnosis of pulmonary LCDD, such that patients are monitored for lung dysfunction and assessed for systemic disease involvement, which can significantly impact mortality and morbidity in affected individuals.

Histological transformation is an important mechanism of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer. Compared with small cell transformation, acquired squamous transformation is uncommon and remains less well characterized. We report a 52-year-old woman who underwent thoracoscopic left upper lobectomy and wedge resection of the left lower lobe for lung adenocarcinoma in April 2021. Molecular testing identified an EGFR exon 19 deletion and a TP53 c.713G>T (p.C238F) mutation. She received osimertinib, and the interval from treatment initiation to the first clinically and radiologically suspected disease progression was approximately 39 months. After this clinically suspected progression, pemetrexed plus cisplatin achieved a partial response. In August 2025, an enlarged left supraclavicular lymph node was detected, and re-biopsy confirmed squamous cell carcinoma. Systemic evaluation did not reveal evidence of a second primary malignancy. Molecular testing of the squamous lesion identified the same EGFR exon 19 deletion and TP53 mutation as those in the primary lung adenocarcinoma, providing molecular evidence consistent with a shared tumor origin and favoring acquired squamous histological transformation over a second primary squamous cell carcinoma. The patient subsequently received carboplatin, nanoparticle albumin-bound paclitaxel, and tislelizumab, achieving a radiologic partial response followed by stable disease during maintenance tislelizumab. This case highlights acquired squamous histological transformation as a rare resistance pattern after long-term osimertinib treatment. Re-biopsy and molecular comparison are important for distinguishing histological transformation from a second primary tumor. The observed response to platinum-taxane chemotherapy combined with tislelizumab should be interpreted cautiously because the relative contributions of chemotherapy and immunotherapy cannot be determined from a single case.

Paraneoplastic syndromes (PNS) are frequently misdiagnosed as independent neurological, endocrine, cutaneous, or rheumatic immune disorders due to their low incidence, highly variable, and complex clinical presentations. Currently, when faced with clinically unexplainable phenomena, PNS is seldom considered in the differential diagnosis. A 68-year-old non-smoking Chinese male presented with insidious digital clubbing in 2021 and refractory cutaneous eruptions in 2023, which were initially diagnosed as granulomatous rosacea and erythroderma. However, treatment with ketotifen, cetirizine, and the immunosuppressant cyclosporine led only to partial regression of the rash, with persistent pruritus. Approximately 3 years after the insidious onset of digital clubbing and 1 year after the skin lesions flared, in April 2024, chest PET/CT scan revealed a mass in the left lower lobe and a nodule in the dorsal segment of the right lower lobe. A biopsy confirmed extensive-stage small cell lung carcinoma (SCLC).His dermatological manifestations, which progressed to edema and dysphagia, and ancillary examination results were subsequently attributed to a paraneoplastic dermatomyositis-like syndrome. Chemotherapy for SCLC resulted in resolution of the skin lesions and disease control. This case underscores the critical role of PNS as an early indicator of occult malignancy and highlights the therapeutic challenges in managing paraneoplastic dermatomyositis-like syndrome.

BACKGROUND Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare and recently described histiocytic neoplasm characterized by ALK gene rearrangements. Several ALK fusion partners have been reported, particularly in patients with multisystem disease. We report the first case of single-site ALK-positive histiocytosis involving a TFG-ALK fusion, a rearrangement previously linked to disseminated disease. CASE REPORT A man in his 50s with obesity, obstructive sleep apnea, diabetes mellitus, hypertension, coronary artery disease, and a 40-pack-year smoking history underwent computed tomography for lung cancer screening; the results showed a solitary 1.6-cm left lower lobe pulmonary nodule. Positron emission tomography demonstrated hypermetabolic activity confined to the lesion. He subsequently underwent video-assisted thoracoscopic wedge resection with mediastinal lymphadenectomy. Histopathologic evaluation revealed a well-circumscribed spindle cell neoplasm expressing histiocytic markers CD4, CD68, and CD163, with cytoplasmic ALK positivity. A TFG-ALK gene fusion was detected using Archer FusionPlex Pan Solid Tumor panel testing with anchored multiplex polymerase chain reaction via Illumina NextSeq 500. Immunohistochemical and flow cytometric studies excluded alternative ALK-rearranged neoplasms, including inflammatory myofibroblastic tumor, anaplastic large cell lymphoma, and ALK-positive diffuse large B-cell lymphoma. The patient received no systemic therapy and remains disease-free on radiographic surveillance. CONCLUSIONS To our knowledge, this case represents the first reported instance of single-site ALK-positive histiocytosis with a TFG-ALK fusion. It expands the molecular and clinical spectrum of this rare entity, suggesting that certain ALK fusion partners are associated with localized disease and an indolent clinical course. Recognition of such presentations is essential to avoid unnecessary systemic therapy.

Pulmonary tuberculosis (TB) remains a major global health concern and may present with radiographic and laboratory findings that complicate timely diagnosis. Interferon-gamma release assays (IGRAs), including QuantiFERON-TB Gold, are blood tests that measure T-cell immune sensitization to Mycobacterium tuberculosis antigens; they do not distinguish latent infection from active disease and cannot exclude active TB. We report a 23-year-old immunocompetent Venezuelan-born man who presented with fever, night sweats, productive cough, and intermittent hemoptysis after approximately seven months of respiratory symptoms. Chest imaging demonstrated multilobar cavitary disease involving both upper lobes and the left lower lobe. Despite a negative QuantiFERON-TB Gold result, two sputum acid-fast bacilli smears were positive, M. tuberculosis nucleic acid amplification testing was positive, and mycobacterial culture confirmed the M. tuberculosis complex. The patient was placed in airborne isolation and treated with rifampin, isoniazid, pyrazinamide, and ethambutol. Public health authorities coordinated directly observed therapy, contact investigation, and outpatient sputum monitoring. This case demonstrates that a negative IGRA cannot rule out active pulmonary TB and that atypical multilobar cavitation should not lower clinical suspicion when epidemiologic, clinical, and microbiologic findings support the diagnosis.

Pulmonary neuroendocrine tumors are uncommon malignancies, and cutaneous metastasis as the initial presentation is exceedingly rare, often leading to diagnostic delays due to nonspecific clinical features. We reported a case of a 57-year-old male presenting with multiple progressively enlarging, painless cutaneous and subcutaneous nodules on the scalp and left chin without accompanying respiratory and constitutional symptoms. The lesions were initially treated as benign dermatological conditions without improvement. Excisional biopsy of a chin lesion demonstrated dermal infiltration by atypical polygonal cells with neuroendocrine morphology and dermal lymphatic invasion. Immunohistochemistry showed positivity for synaptophysin, cytokeratin 7 (CK7), and Cam5.2, consistent with neuroendocrine carcinoma. Contrast-enhanced computed tomography identified a heterogeneously enhancing mass in the left lower lobe of the lung with widespread metastatic disease. Further evaluation with Gallium-68 DOTATATE positron emission tomography/computed tomography, a somatostatin receptor-targeted imaging study, demonstrated avid lesions in the lung, lymph nodes, subcutaneous tissue, omentum, and skeleton. The patient was treated initially with octreotide hormone therapy. The patient had disease progression; therefore, therapy was changed to carboplatin and etoposide. This case highlights that unexplained skin lesions may present as the initial manifestation of an underlying visceral malignancy, signifying the role of early biopsy and comprehensive imaging to enable timely diagnosis and management of aggressive pulmonary neuroendocrine tumors.

Pulmonary disease caused by Mycobacterium avium complex (MAC) most often occurs in patients with structural lung disease or immunocompromising conditions and typically follows recognized fibrocavitary or nodular-bronchiectatic radiographic patterns. Advanced cavitary disease discovered incidentally in an asymptomatic patient represents an uncommon and diagnostically challenging presentation that may be initially attributed to malignancy, aspiration pneumonia, or endemic fungal infection. We report the case of a 45-year-old man without known immunodeficiency who had alcohol use disorder and active deep vein thrombosis treated with apixaban and presented with acute right groin pain secondary to a reducible inguinal hernia. Abdominal computed tomography performed during hernia evaluation incidentally demonstrated a 6.9 × 5.3 cm thick-walled cavitary opacity in the left lower lobe with an air-fluid level and bilateral reticulonodular opacities. The patient denied cough, dyspnea, hemoptysis, fever, night sweats, and weight loss. Serial sputum acid-fast bacillus smears were positive, and mycobacterial cultures grew MAC. In the setting of compatible cavitary imaging, these findings fulfilled the American Thoracic Society/European Respiratory Society/European Society of Clinical Microbiology and Infectious Diseases/Infectious Diseases Society of America (ATS/ERS/ESCMID/IDSA) diagnostic criteria for pulmonary MAC disease. Tuberculosis and HIV testing were negative. A respiratory molecular panel was also positive for Haemophilus influenzae. Because bacterial cultures showed no growth, this finding was interpreted as a possible coinfection rather than a confirmed bacterial infection. Given the leukocytosis and bilateral infiltrates, intravenous ceftriaxone was initiated empirically. However, MAC-directed multidrug therapy was complicated by two pharmacologic barriers: the risk of reduced apixaban exposure with rifabutin-containing therapy and a baseline corrected QT interval of 512 ms, limiting routine macrolide use. The patient was therefore transferred to a tertiary care center for multidisciplinary regimen selection. This case underscores that incidental cavitary pulmonary lesions demand systematic microbiologic evaluation regardless of symptom burden and that early pharmacologic risk assessment is essential when standard MAC therapy is constrained.

Clazosentan, a selective endothelin-A (ET-A) receptor antagonist, is used to prevent cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Although pulmonary edema and fluid retention are recognized adverse effects, hypoxemia associated with atelectasis has not been described. Endothelin-1 contributes to hypoxic pulmonary vasoconstriction (HPV), which preserves ventilation-perfusion (V/Q) matching by diverting blood flow from poorly ventilated regions; pharmacologic ET-A blockade may attenuate HPV, increasing intrapulmonary shunt and impairing oxygenation. We report a man in his 60s with aneurysmal SAH (World Federation of Neurosurgical Societies [WFNS] I, Fisher 3) who underwent clipping surgery and postoperative clazosentan infusion (10 mg/h, standard Japanese dosage). On day 7 of infusion, hypoxemia (SpO2 < 90% room air) developed; on day 8, arterial blood gas showed PaO2 62.5 mmHg with a PaO2/FiO2 (P/F) ratio of 109. Chest computed tomography (CT) demonstrated right lower-lobe atelectasis without pulmonary edema or pleural effusion, and echocardiography showed normal cardiac function. Clazosentan was discontinued and corticosteroid therapy initiated, after which oxygenation improved and the atelectasis resolved. The patient was extubated on day 18 and discharged with good neurological recovery. This case illustrates a plausible mechanism whereby ET-A receptor blockade suppresses HPV, exacerbating V/Q mismatch in the presence of segmental atelectasis. Improvement after drug withdrawal supports this association. Clinicians should recognize that hypoxemia during clazosentan therapy may occur independently of fluid overload and warrants early respiratory evaluation.

Lung cancer associated with cystic airspaces (LCCA) is a rare and distinct subtype of lung cancer. Patients are often without specific clinical symptoms in the early stage, and the radiological features can be easily confused with pulmonary bullae, benign pulmonary cysts, and other cystic lung lesions, resulting in a high rate of missed diagnosis and misdiagnosis. We report the case of a middle-aged woman with LCCA pathologically confirmed following surgical resection. A chest computed tomography (CT) scan performed during a routine health examination initially revealed an air-containing lesion adjacent to the oblique fissure in the right lower lobe, measuring approximately 1.1 cm×0.8 cm. Serial CT examinations over a 12-year period demonstrated gradual evolution of the lesion, with the development of a lobulated contour, interlobar pleural indentation, and vascular convergence, raising suspicion for malignancy. The patient subsequently underwent surgical resection. Based on histopathological and immunohistochemical findings, the lesion was finally diagnosed as invasive lung adenocarcinoma (lepidic predominant, 60%; acinar, 30%; papillary, 10%). No evidence of tumor recurrence or metastasis was observed during postoperative outpatient follow-up.

A 77-year-old man was admitted due to radiologic suspicion of right hilar tumor progression and newly developed right-sided pleural effusion. He had known NSCLC of the left lower lobe (keratinizing squamous cell carcinoma), initially staged T4N1M1c (contralateral lesion and hepatic metastasis), stage IVb. Comorbidities included COPD II, peripheral arterial disease, coronary artery disease, hypertension, and type 2 diabetes. Current oncologic therapy consisted of carboplatin, paclitaxel, and pembrolizumab.The patient presented with exertional dyspnea and reduced breath sounds with dullness to percussion at the right lung base. Bronchoscopic re-biopsy (EBUS-TBNA and transbronchial biopsy) was performed. Pleural cytology was negative for malignancy; therefore, thoracoscopy was conducted, revealing chronic pleuritis without malignant involvement.

Soft tissue synovial sarcoma is a rare mesenchymal tumor that mainly affects deep soft tissues of the extremities in young adults, but it is also recognized as a primary pulmonary neoplasm. Primary pulmonary synovial sarcoma (PPSS) accounts for less than 0.5% of all primary lung malignancies. Unlike other primary lung malignancies, PPSS has no known association with tobacco exposure and environmental carcinogens. It is characterized by an aggressive clinical course and a defining chromosomal translocation, t(X,18)(p11;q11), resulting in the fusion of the SYT gene on chromosome 18 with SSX1 or SSX2 on chromosome X. A 60-year-old woman with a 50-pack-per-year smoking history presented with gross hematuria and was incidentally found to have a right lower lobe lung mass on chest radiography. Positron emission tomography (PET) and computed tomography (CT) demonstrated a 7.1 x 6.6 cm supradiaphragmatic pulmonary mass without lymphadenopathy or distant metastases. Biopsy confirmed synovial sarcoma. Due to borderline pulmonary function, she was initially deemed a poor surgical candidate and referred to a sarcoma specialty center, where neoadjuvant chemotherapy with Adriamycin, Ifosfamide, and Mesna was initiated locally. After four cycles, follow-up imaging showed tumor reduction greater than 30% and no evidence of metastatic disease. Her lung function improved following smoking cessation, and she subsequently underwent a right lower lobectomy, with pathology revealing a largely necrotic synovial sarcoma with peripheral residual tumor, negative margins, and negative lymph nodes. Then, 4 months postoperatively, surveillance imaging revealed widespread metastatic sarcoma with innumerable pulmonary metastases, a large omental mass, and invasion of the right supraspinatus and scapula. Palliative management was initiated, but subsequent imaging demonstrated metastatic disease progression, showing more than 50 metabolically active pulmonary nodules, omental carcinomatosis, peritoneal metastases, and abdominopelvic ascites. This case highlights the aggressive clinical course of PPSS despite optimal multimodal therapy including neoadjuvant chemotherapy and complete surgical resection. Recurrence and metastasis remain common even following apparent initial response to therapy, underscoring the need for improved targeted systemic therapies and broader access to clinical trials for this rare malignancy.