LELC, originally described in the nasopharynx,refers to undifferentiated carcinoma with predominant lymphocytic infiltration. Zhu et al. reported that LELC mostly originates from organs of fore-gut. Recently, there are several reports describing some cases suffer from LELC of other organs such as rectum,prostate and colon[14–16]. It was first reported originating from lung in 1987 by Begin as a large-cell carcinoma. Later,pulmonary LELC was found to be similar to poorly differentiated squamous cell carcinoma. In 2015, the World Health Organization’s histological classification of lung tumors classified pulmonary LELC as an untyped tumor.
Primary pulmonary LELC has been proven to be strongly associated with EBV infection in Asians through detecting high levels of antibodies against EBV-capsid antigens in the patient’s serum. The association was also observed in some specific geographic groups including Chinese,Japanese,and Eskimos later. However, the situation seemed to be different in western patients. In Claudia’s report the EBV genome was not detected through ISH in any of patients’ serum with pulmonary LELC from western countries. Maybe the etiology of pulmonary LELC differs among races and geography.Primary pulmonary LELC occurs mostly in young Asians. Otherwise, the median age at diagnosis of the western patients is 65. Comparing to other lung cancers,smoking don’t affect the morbidity of LELC that apparently. Futhermore, there seems to be no differences between sexs.
To diagnose primary pulmonary LELC, chest CT scan should be the first chosen exam. Ma et al. concluded that the CT scan features of pulmonary LELC usually appeared as a large, central, well defined and lobulated mass and enhanced CT usually showed inhomogeneous or homogeneous enhancement of the mass with vascular or bronchial encasement. PET imaging is wildly used to investigate the malignant potential of solitary pulmonary nodule which is more than 8mm in diameter. LELC is an 18F-FDG-avid tumour, PET imaging can provide valuable information on the disease detection, staging and treatment response evaluation. The role that serum tumor markers play in the diagnoses of pulmonary LELC is depressing. Ying et al. reported neuron-specific enolase and cytokeratin 19 fragment 21-1 elevated in half of their cases, but there still lacks of adequate proofs to certify the association between tumor markers and pulmonary LELC. In our case, the serum levels of tumor markers were normal at the time pulmonary LELC was diagnosed. Roger et al. reported free circulating serum EBV-DNA could be detected in most patients with untreated or relapsed pulmonary LELC. However, it’s impractical to use serum EBV-DNA as a tumor marker for diagnosis, cause pulmonary LELC is a relatively rare subtype of lung cancer in clinic. Perhaps serum EBV-DNA can be used to monitor therapy response or relapse surveillance of pulmonary LELC.
There is no unified therapeutic schedule for pulmonary LELC, and most studies published about this disease follow the National Comprehensive Cancer Network guidelines of NSCLC. Complete resection is the first choice for patients with pulmonary LELC at early stage (stage I and stage II) . Although pulmonary LELC is sensitive to chemotherapy due to the similar histological and biological characteristics with NPC, adjuvant chemotherapy doesn’t improve the postoperative overall survival (OS) of the patients with early stage disease[28, 29]. However, adjuvant chemotherapy has been identified to significantly improve the prognosis for the patients at stage IIIA who received complete resection[26, 28]. As for the patients at advance stage, chemotherapy can get a good treatment response. It’s reported that platinum-based doublets chemotherapy for the advance stage patients could prolong the OS as well as radical surgery to the early stage patients under a 67 months median follow-up duration. If radiotherapy can improve the prognosis of pulmonary LELC is still uncertain. Qi et al. recently published a retrospective analysis result including 922 non-nasopharyngeal LELC patients indicating no significant improvement of cancer-specific survival was observed intervened by radiotherapy. However, this research didn’t uniquely analyze pulmonary LELC cases, and the diversity among different stages wasn’t discussed forward either. Target therapy in pulmonary LELC seems to be unpromising. Epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement were demonstrated uncommon in pulmonary LELC in previous researches[31, 32]. Immunotherapy may have a good prospect in treating pulmonary LELC according to recent studies. Chang et al. detected PD-L1 expression in 66 patients of pulmonary LELC and the positive rate (defined as > 5%) was 75.8%. And Wu et al. reported high level of PD-L1 expression (defined as ≥ 50%) was found in 61% (36/59) of patients. A recent study compared therapeutic effect of immunotherapy with chemotherapy in advanced stage patients, and a longer progression-free survival (PFS) was achieved in the former group. The further large sample clinic studies of immunotherapy of pulmonary LELC are needed. As for prognosis, most former studies demonstrated that of pulmonary LELC was better than other NSCLCs. He et al. reported that the OS rate by 1, 3 and 5 years of patients with pulmonary LELC could reach 85.6%, 68.9% and 59.5%, comparing to 39.1%, 18% and 12.9% of other NSCLCs.
Idiopathic inflammatory myopathies (IIM), collectively known as myositis,are heterogeneous disorders characterized by muscle weakness and muscle inflammation. PM, which is one of the most common subgroups of IIM, should be suspected in any patient who presents with progressive, varying degrees of symmetric proximal limb and truncal muscle weakness. As for myositis-specific antibodies, serum Anti-Jo-1 autoantibody is usually detected positive in the patients with IIM. In our case, however, Anti-nRNP/Sm is the only positive finding. Other laboratory measurements such as the serum levels of creatine kinase, LDH, ALT and AST usually elevate just the same as our case. The patient in our case is diagnosed with PM due to her age, muscle weakness, laboratory measurements according to 2017 European League Against Rheumatism/ American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Therapeutically, glucocorticoids are used as the first-line treatment, and concomitant treatment with steroid-sparing immunosuppressive agents can reduces the relapse risk during glucocorticoid tapering and the initial doses of glucocorticoids[40, 41]. However, the muscle weakness and pain of the patient didn’t relieve at all after more than 20 days glucocorticoid therapy. Thus, the traditional drug therapy may make no sense when PM is accompanied by cancer.
Catherine et al. reported PM was associated with an increased risk of lung cancer. On the other hand, autoimmune disease as a paraneoplastic syndrome (PNPS) is not rare in lung cancer,and the incidence rate is about 4.7%. Thus, when a patient visits outpatient suspected with IIM, chest CT scan should be performed routinely. In our case, the diagnosis and treatment of the patient were delayed on a certain extent due to the unawareness of the correlation between lung cancer and PM. Previous studies showed that PNPS among patients with SCLC was higher than NSCLC cause all SCLC were derived from neuroendocrine cells which could secrete peptide hormones. Pulmonary LELC is a kind of NSCLC and belongs to squamous cell lineage immunohistochemically. Till now, there’s no research having found particular peptides, hormones or cytokines secreted by LELC tumor cells may lead to PNPS. And here are only two case reports about pulmonary LELC with PNPS can be found.Zhu et al. reported a patient diagnosed with hypertrophic pulmonary osteoarthropathy (HPOA) by emission computed tomography (ECT) which considered to be PNPS of pulmonary LELC.Though the relief of HPOA couldn’t be evaluated cause the patient refused to be reexamined by ECT after surgery for the primary tumor. The other report was about a patient diagnosed at IIIb clinical stage accompanied with erythema elevatum diutinum(EED). The skin lesions didn’t fade at all after topical steroid treatment.Combination of chemotherapy and radiotherapy achieved over 3 years disease-free survival and marked relief of EED. We concluded some data of the two cases in Table 1. Review our case, the patient’s muscle weakness and pain relieved gradually during the comprehensive therapy of her tumor. The PM related laboratory measurements such as creatine kinase, MB and Anti-nRNP/Sm also decreased obviously when reexamed after radiotherapy. And the postoperative EMG showed minimal peripheral nerves injuried and atypical myogenic damaged which meaned the her muscular damage relieved a lot. Here we can see, it’s the primary tumor should be treated fisrtly rather than the PNPS caused by it. Though Dumansky et al. concluded PNPS negatively affected the survival rates of patients with lung cancer, the prognosis of pulmonary LELC patients with PNPS seemed prospective.