We herein report a case of breast cancer in a 74-year-old woman treated with exemestane as fourth-line hormonal therapy and bone-modifying agents for long time. She suddenly developed a right femoral shaft fracture during treatment. Her femoral fracture had a beaking sign on radiogram. Given this finding, her fracture was ultimately diagnosed as atypical femoral fracture (AFF). In this case, it was difficult to recognize the difference between groin pain as a prodromal symptom of AFF and that due to an adverse reaction to hormonal therapy. Therefore, clinicians should recognize the difficulty of this differentiation and consider the situation with caution.

Common dermatological side-effects associated with erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), include pruritus and skin rash, which are mediated by substance P, leading to the occasional discontinuation of cancer treatment. Aprepitant is an antagonist of neurokinin-1 receptor, through which substance P activates the pruritogens. Thus, aprepitant is expected to offer a promising option for the treatment of erlotinib-induced pruritus. However, the appropriate treatment schedule for aprepitant administration is under consideration. Here, we discuss the need for flexible adjustment of the treatment schedule for aprepitant administration against erlotinib-induced refractory pruritus and skin rush. A 71-year-old female smoker presented with stage IV EGFR-mutated lung adenocarcinoma. She was started on erlotinib at 150 mg/day. However, by 28 days, severe pruritus and acneiform skin rush resistant to standard therapies occurred, resulting in the interruption of erlotinib therapy. After recovery, she was restarted on erlotinib at 100 mg/day. However, severe pruritus and skin rush developed again within 2 weeks. Then, we started the first 3-day dose of aprepitant (125 mg on day 1, 80 mg on day 3, and 80 mg on day 5) based on the results of the previous prospective study, which showed the success rate of 100% with at least the second dose of aprepitant. However, the pruritus and skin rush exacerbated again within 4 weeks. Therefore, we started the second 3-day dose of aprepitant, but in vain. At this point, as the patient-centered medicine, bi-weekly schedule of the 3-day dose of aprepitant was considered and, then, adopted. As the results, the pruritus and skin rush remained well-controlled throughout the subsequent treatment with erlotinib.

For sebaceous carcinoma (SC), a rare malignant tumor, no standard chemotherapy regimen for patients with distant metastasis has been studied. We experienced a case of eyelid SC with multiple lung metastases that responded to combination chemotherapy with carboplatin and paclitaxel with 11-month progression-free survival (PFS). This patient also responded to second-line treatment with docetaxel, another taxane, with 7-month PFS, resulting in at least 18 months of survival at the time of reporting. This report shows that taxane-based chemotherapy may be effective for advanced SC, for which no standard therapy has been established.

We encountered a case of primary lung cancer complicated with membranous nephropathy as primary nephrotic syndrome. Because treatment approaches vary greatly for primary and secondary nephrotic syndrome, a renal biopsy was performed for diagnosis. Much time was required to make a definitive diagnosis of primary nephrotic syndrome, as opposed to paraneoplastic nephrotic syndrome. Consequently, the subsequent chemotherapy was ineffective and caused significant toxicity due to reduced performance status (PS) and progression of hypoalbuminemia. Therefore, it is imperative that a diagnosis be made and treatment be initiated without delay before PS declines and hypoalbuminemia progresses.

In lung cancer, several potential mechanisms of intrinsic and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been explored, including mesenchymal-epithelial transition factor (MET) signaling pathway activation. On the other hand, vascular endothelial growth factor (VEGF) production of EGFR-mutated lung cancer cells is stimulated by predominantly activated MET signaling pathway. Therefore, the inhibition of VEGF axis as the downstream target of MET signaling pathway seems promising. Here, for the first time, we report the potential efficacy of combination therapy with bevacizumab and erlotinib in an EGFR-mutated NSCLC patient with MET amplification who showed intrinsic resistance to initial EGFR-TKI therapy. The patient was a 60-year-old male smoker, showing performance status (PS) 2, who presented with stage IV lung adenocarcinoma (cT4N2M1a) harboring the EGFR exon 19 deletion mutation. He was started on gefitinib at 250 mg/day. However, by 28 days, his symptoms further deteriorated along with the increased tumor size, resulting in PS 3. Then, repeat biopsy was performed, showing the positive MET amplification and the preserved EGFR exon 19 deletion mutation. Therefore, on the basis of the potential efficacy for activated MET signaling pathway as well as the confirmed safety by the known phase II trial for EGFR-mutated patients, the patient was started on combination therapy with bevacizumab at 15 mg/kg every 3 weeks plus erlotinib at 150 mg/day. By 21 days, his symptoms gradually improved along with the decreased tumor size, resulting in better PS with no severe toxicities.

The patient was a 66-year-old woman. An induration of approximately 15 mm in size that accompanied redness was palpable in the umbilical fossa. She did not respond to 1-month antibiotic treatment provided by the previous physician. For this reason, a biopsy of the site was performed with the possibility of neoplastic disease in mind, resulting in the detection of adenocarcinoma. Subsequent detailed whole-body examination revealed advanced gastric cancer and peritoneal dissemination, and the induration in the umbilical fossa was diagnosed as a direct infiltration from the peritoneal dissemination. Metastasis or infiltration of malignant tumor to the umbilicus is called Sister Mary Joseph's nodule (SMJN), and considered as a sign of poor prognosis. However, this case was successfully treated and achieved a long-term prognosis by the early diagnosis of SMJN. In routine clinical practice, it is considered necessary to examine patients carefully, as not to overlook SMJN.

In stage IV non-small cell lung cancer (NSCLC) patients with multiple metastases, a various pattern of disease progression is observed, including the growth of only primary site, the growth of only pre-existing metastatic site, or the appearance of new metastatic site. The aim of our study is to evaluate the detailed recurrence pattern in patients with stage IV NSCLC, and is also to evaluate whether a specific patient's population exists whose disease progression is well controlled by the additional local therapy, such as surgery or radiotherapy to the primary or pre-existing metastatic site, during or after the systemic chemotherapy. NSCLC patients in stage IV admitted to our hospital from 2012 to 2014 were examined retrospectively. The recurrence pattern was classified into the following groups; the growth of primary site, the growth of pre-existing metastatic site, or the appearance of new metastatic site. Furthermore, progression-free survival (PFS), overall survival (OS), and new lesion-free survival (NFS) of these groups were examined, respectively. Patients treated with chemotherapy for stage IV NSCLC were 114 cases. The median age was 70 years old, and male was 74 cases. The number of platinum-based combination regimen was 71 cases, monotherapy was 16 cases, epidermal growth factor receptor tyrosine kinase inhibitor was 25 cases, crizotinib was two cases. In the first-line chemotherapy, median PFS, median OS and median NFS in all patients were 172 days, 417 days and 270 days. Median PFS, median OS and median NFS in patients for the growth of primary site were 235 days, not reached and not reached. Median PFS, median OS and median NFS in patients for the growth of pre-existing metastatic site were 171 days, 250 days and 205 days. Median PFS, median OS and median NFS in patients for the appearance of new metastatic site were 149 days, 423 days and 149 days. The prognosis of the appearance of new metastatic site group seems to be worse than the growth of primary site group in the pattern of disease progression in the first-line chemotherapy. And the prognosis of the growth of pre-existing metastatic site group seems to be worse than the appearance of new metastatic site group. In the stage IV NSCLC therapy, there is a possibility that the treatment outcomes will be improved according to well controlled the pre-existing metastatic site by the additional local therapy.

The patient was a 69-year-old male who had started experiencing acute-onset pain in both shoulder joints and edema of both hands and feet. His symptoms progressively worsened within 1 month. Laboratory data indicated elevated CRP and erythrocyte sedimentation rate despite the normal range of antinuclear antibodies and rheumatoid factor and normal organ function. Furthermore, imaging data of the hand indicated synovitis without bone erosions. Meanwhile, chest CT revealed a lung tumor, leading to a diagnosis of primary lung adenocarcinoma with EGFR mutation (cT2aN3M0, stage IIIB). Based on these findings, he was diagnosed as suffering from paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Thereafter, his symptoms disappeared as the tumor size was rapidly decreased by gefitinib therapy for lung adenocarcinoma. Currently, RS3PE syndrome can be classified as a vascular endothelial growth factor (VEGF)-associated disorder. Given that his symptoms improved by chemotherapy, the present case further supported the possible hypothesis that paraneoplastic RS3PE syndrome might be caused by tumor-induced VEGF. Therefore, the present case suggested that the symptoms of acute-onset joint pain accompanied by pitting edema in elderly patients should be considered suspicious for a malignant tumor, thereby warranting a detailed full-body examination.

A 73-year-old man, followed for prostatic hyperplasia, developed submandibular gland cancer. Initially, because of the concurrent presence of elevated serum prostate-specific antigen (PSA) and multiple bone metastases, he was clinically determined as having stage IV prostate cancer in addition to stage II submandibular gland cancer, and radical surgery for his submandibular gland cancer was performed first. However, subsequent detailed examinations of the prostate gland showed no prostate cancer, and a diagnosis of advanced submandibular gland cancer with increased PSA and multiple bone metastases was established. Serum PSA is highly specific for prostate diseases and is widely used as a tumor marker of prostate cancer. However, clinicians should be aware that, in patients with non-prostate cancer, the detection of increased PSA and multiple bone metastases does not necessarily indicate the concurrent presence of prostate cancer.

A 40-year-old man with a diagnosis of lung adenocarcinoma (cT4N3M1c, stage IVB) experienced worsening of lymphangitic carcinomatosis in the right lung and right pleural effusion after receiving 1 cycle of first-line chemotherapy consisting of cisplatin and pemetrexed. Bevacizumab was thus added from the second cycle of the cisplatin-pemetrexed regimen, leading to a marked improvement in pulmonary lymphangitic carcinomatosis and a decrease in pleural effusion. Subsequently, maintenance therapy consisting of pemetrexed and bevacizumab was continued, successfully leading to long-term progression-free survival. Generally, pulmonary lymphangitic carcinomatosis shows poor prognosis because of poor response to chemotherapy. However, recent studies have been elucidating the role of the vascular endothelial growth factor A (VEGF-A)/VEGF receptor-2 pathway in pulmonary lymphangitic carcinomatosis. Therefore, bevacizumab is expected to be beneficial in the treatment of this pathological condition.

A 50-year-old man with lung adenocarcinoma (c-T1aN2M1b) experienced reddish purpura mainly on the lower legs after receiving 12 cycles of second-line chemotherapy with docetaxel. There was tumor enlargement on computed tomography performed to assess the therapeutic response, so paraneoplastic IgA vasculitis was considered. IgA vasculitis was diagnosed based on a biopsy of the skin lesion and histology of an upper gastrointestinal hemorrhagic mucosal erosion. As IgA vasculitis can lead to serious gastrointestinal or systemic complications, IgA vasculitis should be considered as a differential diagnosis for rashes in patients with malignancy.