With an estimated 1.88 million new cases and 0.92 million deaths in 2020, colorectal cancer accounts for nearly one-tenth of all new cancer and cancer-related deaths worldwide. Nearly half of the patients of colorectal cancer are diagnosed with metastatic or inoperable disease with a very dismal 5-year survival rate. Chemotherapy, targeted therapy, and immunotherapy have been used to treat metastatic disease, either alone or in combination. We present a case of recurrent metastatic colon carcinoma with KRAS exon 2 mutation and high microsatellite instability that was treated with a combination regimen of bevacizumab, capecitabine oral chemotherapy, and pembrolizumab immunotherapy. At nearly 5 years of treatment, the patient is alive with good performance status and improved quality of life owing to a favorable response to the molecular profiling-based treatment approach.

A 75-year-old woman was admitted to our hospital with suspected gastrointestinal perforation and underwent emergency surgery. Bladder perforation was revealed during the surgery, and she was referred to our department. We detected a tumor on the apex of the bladder and performed partial resection of the bladder. Based on histopathological examination, a diagnosis of urachal cancer was established. Gemcitabine and cisplatin (GC) therapy was administered as an adjuvant therapy because of the high risk of peritoneal dissemination. She had the purulent spondylitis and gluteus medius abscess at the first course of GC therapy. We stopped GC therapy within the first course due to the adverse events and decreased performance status. Computed tomography revealed tumor recurrence in the pelvis three months after discontinuation of GC therapy. As the companion diagnostics revealed MSI-High, we administrated pembrolizumab. She was taking prednisolone 5 mg for SLE, but stable disease was observed after 5 courses of pembrolizumab. However, pembrolizumab was discontinued for eight months due to the stent graft insertion for the common iliac artery aneurysm. She had progressive disease after eight months interval of treatment. We restarted pembrolizumab but she was hospitalized for tumor fever after a total of eight courses. The patient died a month later. This seems to be the first case wherein pembrolizumab was administered for urachal cancer with MSI-High.

BACKGROUND: Malignant tumors with rhabdoid features are rare, highly aggressive, and some of them are characterized by SMARCB1 (INI1) loss. Although cases of rhabdoid carcinoma are extremely rare, its occurrence in the colon has been reported previously.
METHODS: A 71-year-old Japanese female patient presented with loss of appetite, fatigue, and weight loss. Computed tomography demonstrated a tumor in the right colon that infiltrated the surrounding kidneys and swelling of the left supraclavicular and periaortic lymph nodes. Laparotomy revealed that the tumor was unresectable because it had directly invaded the head of the pancreas and duodenum. Therefore, ileocecal vascularized bulky lymph nodes were sampled, and gastrojejunostomy with Braun\'s anastomosis and ileotransversostomy were performed as palliative procedures. Histopathological examination of the lymph nodes revealed that the neoplastic cells had rich eosinophilic cytoplasm and eccentrically located large nuclei characteristic of rhabdoid carcinoma. In addition, these neoplastic cells lacked SMARCB1 expression; therefore, the patient was diagnosed with SMARCB1-negative rhabdoid carcinoma. The postoperative course was uneventful. Molecular analysis confirmed that the neoplastic cells had high microsatellite instability (MSI); therefore, two cycles of pembrolizumab were administered. However, no clinical benefit was noted, and the patient died 3 months postoperatively.
CONCLUSIONS: This is the first report of a case of SMARCB1-negative rhabdoid colon carcinoma with high MSI treated with pembrolizumab. Rhabdoid carcinoma is highly aggressive; therefore, additional studies are required to determine the therapeutic strategy for SMARCB1-negative rhabdoid colorectal carcinoma.

BACKGROUND: Immune checkpoint inhibitors are reportedly effective in treating microsatellite instability (MSI)-high gastric cancer. There are a few case reports of conversion surgery (CS) with nivolumab but none with pembrolizumab. Herein, we describe a patient with MSI-high gastric cancer who was successfully treated with pembrolizumab and underwent CS with a pathological complete response.
METHODS: A 69-year-old man was diagnosed with stage III gastric cancer (T3N2M0) based on contrast-enhanced computed tomography, which revealed a neoplastic lesion and enlarged perigastric lymph nodes in the gastric lesser curvature. The anterior superior lymph node of the common hepatic artery (CHA) was determined to be unresectable due to invasion of the pancreatic head and CHA. Histopathologically, the biopsied tissue showed moderately differentiated adenocarcinoma, then determined to be MSI-high. After three courses of mFOLFOX6 therapy, the patient was diagnosed with progressive disease. Since one course of paclitaxel plus ramucirumab therapy caused grade 3 fatigue, his second-line therapy was switched to pembrolizumab monotherapy. After three courses, the primary tumor and perigastric lymph nodes had shrunk, and it was determined as a partial response. The anterior superior lymph node of the CHA became resectable based on the improvement of infiltration of the pancreatic head and CHA due to shrinkage of the lymph node. Tumor markers remained low; hence, distal gastrectomy plus D2 lymphadenectomy was performed at the end of six courses. Anterior superior lymph node of the CHA was confirmed by intraoperative ultrasonography, and the resection was completed safely. The gross examination of the resected specimen revealed an ulcer scar at the primary tumor site. The histopathological examination showed no viable tumor cell remnants in the primary tumor, which had a grade 3 histological response, and resection margins were negative. The lymph nodes showed mucus retention only in the anterior superior lymph node of the CHA, indicating the presence of metastasis, but no viable tumor cells remained. The patient commenced 6 months of adjuvant pembrolizumab monotherapy 3 months after surgery. Twenty months after surgery, there was no evidence of recurrence.
CONCLUSIONS: Conversion surgery following pembrolizumab monotherapy has a potential utility for the treatment of MSI-high gastric cancer.

A 76-year-old man with epigastric pain developed 1 month earlier was referred to our department for additional screening and treatment after abdominal ultrasound revealed a mass shadow in the pancreatic head and liver. Blood biochemistry revealed signs of mild jaundice and hepatic dysfunction. Abdominal contrast-computed tomography revealed an irregular hypodense mass with poor enhancement in the pancreatic head and several hypodense nodules in the liver. Endoscopic examination revealed duodenal infiltration signs. The biopsied duodenal mucosa contained atypical cells with high nuclear-to-cytoplasmic ratios; the cells stained positive for CD56, chromogranin, and synaptophysin, and the Ki-67 index was 90%. Accordingly, pancreatic neuroendocrine carcinoma (PanNEC) was diagnosed. Platinum-based chemotherapy (6 courses) and streptozotocin (10 courses) were adopted as the first- and second-line regimens, respectively. However, the patient showed progressive disease (PD). Pembrolizumab was added as a third-line regimen (13 courses) after confirming PanNEC with high microsatellite instability (MSI-high). Despite a temporary partial response (PR), the patient showed PD by the end of the 13 courses and died 1 year and 7 months after diagnosis. Although there is no established PanNEC therapy, those with MSI-high may respond favorably to pembrolizumab. Therefore, we should ascertain the MSI status of any PanNEC in routine practice.

Treatment options for unresectable, locally advanced or metastatic penile squamous cell carcinoma (SCC) are limited. Previous studies have shown that 40-62% of patients with penile SCC express PD-L1. We report three cases of locally advanced or metastatic penile SCC treated with pembrolizumab.
Herein, we present three patients with recurrent, locally advanced or metastatic penile SCC who progressed on a platinum-based chemotherapy triplet and were treated with pembrolizumab, administered as part of a phase II clinical trial for rare tumors (NCT02721732). One patient with a microsatellite instability high (MSI-H) tumor experienced a durable partial response to pembrolizumab, underwent surgical consolidation, and remains disease-free 38.7 months later. Two patients experienced progressive disease within 3 months of beginning pembrolizumab. No one experienced a grade 3 or worse treatment-related adverse event.
In sum, single-agent pembrolizumab was well tolerated as salvage therapy in a small cohort of patients with unresectable, locally advanced or metastatic penile SCC. Pembrolizumab produced an objective response in an MSI-H tumor, yet it did not control disease in two patients with MSS penile SCC. Rationale combination therapies, including pembrolizumab, warrant further investigation.
ClinicalTrials.gov identifier: NCT02721732 . Registered March 23, 2016.

OBJECTIVE: The efficacy of pembrolizumab for intrahepatic cholangiocellular carcinoma (IHCCC) is not widely reported.
METHODS: We began pembrolizumab treatment in a 69-year-old male with recurrent IHCCC at 18 months after his surgery because of the proven microsatellite instability (MSI)-high status. The patient had partial response, with an 82.5% reduction at the end of 18 courses. Immunostaining of the primary tumor revealed intra-tumoral infiltration of both PD-1+ and CD8+ T cells, and a low expression of PD-L1.
CONCLUSIONS: Intra-tumoral infiltration of both PD-1+ and CD8+ T cells may be a predictive factor of the efficacy of pembrolizumab. Expression of PD-L1 did not correlate with a therapeutic effect, but the tumor microenvironment of our patient\'s recurrent lesions may have been modified by conventional chemotherapy and CD8+ T cells.

We report a case of colonic adenosquamous carcinoma with MSI-H (microsatellite instability-high) in a 43-year-old male who presented with bowel obstruction due to a circumferential mass involving the descending colon and splenic flexure. Microscopically, it showed poorly differentiated adenocarcinoma with squamous differentiation, tumor infiltrating lymphocytes >3/high-power field, and mild peritumoral lymphocytic response. Immunohistochemistry was equivocal for MLH-1, PMS-2, and MSH-2, with retention of MSH-6 expression. Polymerase chain reaction testing demonstrated MSI-H pattern with instability of BAT-25, BAT-26, and NR-21. Review of the literature revealed only one recently published case of MSI-H adenosquamous carcinoma. The role of MSI in adenosquamous carcinoma pathogenesis is still unknown. In conclusion, MSI testing in colonic adenosquamous carcinoma combined with other MSI-related clinical and histological features is indicated.