Long-term complete response in small cell bladder carcinoma treated with carboplatin, etoposide, and atezolizumab.

BACKGROUND: Small cell bladder carcinoma (SCBC) is a rare and aggressive malignant tumor with no established treatment guidelines. Its treatment algorithm has been based on the small cell lung cancer (SCLC) guidelines. Metastatic SCBC has poor prognosis (even when treated with platinum-based chemotherapy, which is usually used for extensive-disease SCLC). CASE PRESENTATION: Herein, we report a case of a 71-year-old man with SCBC who underwent radical cystectomy and received adjuvant chemotherapy with gemcitabine and cisplatin. However, recurrent tumors were found 6 months postoperatively. The patient was then treated with carboplatin, etoposide, and atezolizumab and achieved complete response. He continues receiving maintenance therapy with atezolizumab monotherapy without any evidence of recurrence over the 12 months follow up. CONCLUSION: To our knowledge, this is the first case of metastatic SCBC where carboplatin, etoposide, and atezolizumab achieved long-term complete response.

Perforation of a Peptic Ulcer in a Hiatal Hernia Into the Left Ventricle With Systemic Air and Food Embolism.

Perforation of a peptic ulcer into the ventricle is uncommon, and the definitive diagnosis is difficult in living patients. We herein report a case of perforation of a peptic ulcer in a hiatal hernia into the left ventricle with systemic air and food embolism. This is the first case report of the perforation diagnosed by computed tomography and confirmed by autopsy. Computed tomography was useful for the diagnosis of perforation into the ventricle.

Efficacy of lorlatinib after alectinib-induced interstitial lung disease in a patient with anaplastic lymphoma kinase-positive non-small cell lung cancer: a case report.

BACKGROUND: Anaplastic lymphoma kinase tyrosine kinase inhibitors are standard therapeutic agents prescribed for anaplastic lymphoma kinase-positive non-small cell lung cancer, and treatment with these agents has been shown to contribute to long-term survival in patients. However, there is no consensus regarding the course of treatment after the onset of anaplastic lymphoma kinase tyrosine kinase inhibitors related drug-induced interstitial lung disease. Here, we present a case of successful lorlatinib treatment after the onset of drug-induced interstitial lung disease caused by alectinib. CASE PRESENTATION: A 57-year-old Japanese man was diagnosed with stage IVB non-small cell lung cancer by bronchoscopy, but gene mutation testing could not be performed because of the small amount of specimen. After diagnosis, first-line therapy with cisplatin/pemetrexed was initiated, but the patient developed renal dysfunction. Bronchoscopy was performed again to guide further treatment, and the non-small cell lung cancer was found to be anaplastic lymphoma kinase positive. Alectinib was started after the onset of progressive disease, but it resulted in drug-induced interstitial lung disease, necessitating alternative treatments. He subsequently received nanoparticle albumin bound paclitaxel, which was halted in view of the renal dysfunction. Thereafter, lorlatinib was administered, which was continued without drug-induced interstitial lung disease relapse. CONCLUSION: Since alectinib can occasionally cause drug-induced interstitial lung disease, as in the present case, lorlatinib may be an option to continue treatment in patients without other treatment alternatives.

Ruptured isolated external iliac artery true aneurysm associated with cystic medial necrosis: report of a case.

We report a case of a ruptured isolated true external iliac artery aneurysm (EIAA). A 78-year-old woman was admitted to our institution in a shock state after the sudden onset of severe pain in the right hypogastric region. A pulsating mass was found in her right lower abdomen. Computed tomography (CT) with contrast medium showed an isolated EIAA, 40 mm in diameter, with a massive retroperitoneal hematoma. She underwent emergency resection of the aneurysm and reconstruction of the affected artery, without any complications. Histological examination confirmed a true aneurysm caused by cystic medial necrosis (CMN). She had no ocular, cardiac, or orthopedic abnormalities. We review the literature on isolated true aneurysms of the external iliac artery, which are extremely rare, and discuss their clinical manifestations.

Gas-filled intradural cyst with migration into the nerve root of the cauda equina.

Only 4 cases of gas-filled intradural cysts of the spine have been reported previously. All cysts were due to intradural herniation of a gas-containing disc. The authors report 2 additional patients with gas-filled intradural cysts that migrated into the nerve root of the cauda equina. After surgical treatment their severe leg pain completely resolved.

Heterogeneous gene alterations in primary breast cancer contribute to discordance between primary and asynchronous metastatic/recurrent sites: HER2 gene amplification and p53 mutation.

The aim of the present study was to clarify differences in genetic events between primary breast cancers and asynchronous metastatic/recurrent lesions, by examining HER2 gene amplification and p53 mutation. The subjects were 44 breast cancer patients with asynchronous metastasis or recurrence. Synchronous metastases were excluded. HER2 overexpression and gene amplification were examined using immunohistochemistry and fluorescent in situ hybridization (FISH). P53 point mutation was examined by immunohistochemistry, laser-captured microdissection, PCR-single-strand conformation polymorphism, and a direct sequencing method. Immunohistochemistry showed that, for HER2, p53, ER and PgR, discordance rates between primary and recurrent tumor were 2 (4.5%), 1 (2.3%), 7 (15.9%) and 10 (22.7%), respectively. Two primary tumors with discordant HER2 overexpression were composed of at least two populations of carcinoma cells, with and without HER2 gene amplification. Distribution of HER2 gene amplification was consistent with protein overexpression. Corresponding recurrent tumors consisted of carcinoma cells without HER2 gene amplification. Of 6 recurrent tumors in which the primary carcinoma had a p53 point mutation, 3 tumors had identical mutations, 1 tumor had a different point mutation, and 2 tumors had no mutation. It was suspected that the latter 3 recurrent tumors comprised a minor component of the primary tumor. In the present study, we examined a large series of asynchronous recurrent tumors. A limited number of these tumors showed discordance between primary and recurrent tumors. Detailed observations revealed that cell populations present in recurrent tumors were also present in the primary tumors, although they comprised a minor component of the primary tumor. Heterogeneity of the primary tumor apparently contributed to discordance.

A case for gastrointestinal stromal tumor (GIST) with reference to its ultrastructure and 'gain-of-function' mutation.

A case for primary gastrointestinal stromal tumor (GIST) is described with reference to its ultrastructural characteristics and mutation within the exon 11 of c-kit gene. A forty-seven years old woman complaining of dysphasia was examined by endoscopy, which depicted a submucosal tumor (70 mm in diameter) with ulcerations at the fundus of the stomach. Histopathologically, the tumor cells had large nuclei and eosinophilic cytoplasm and were frequently during mitosis phase. The tumor cells were immunopositive for KIT, CD 34 and vimentin, suggesting their fibroblast-like characteristics. In contrast, desmin and S-100, a smooth muscle and an enteroglial marker, were not immunopositive within the cells. At least 30 % of the tumor cells possessed MIB-I and 20 % of them possessed p53, which are compatible with fast development of the tumor. By electron microscopy, the tumor cells possessed large oval nuclei, abundant mitochondria, caveolae and smooth endoplasmic reticulums, while no gap junctions were seen on the cells: The tumor cells thus possessed interstitial cells-like characteristics at least in part. DNA mutation search for the tumor cells however realized no gain-of-function mutation within the exon 11 of the c-kit gene, suggesting existence of other mechanism for neoplasmic growth of the tumor cells classified as gastrointestinal stromal tumors.

A case of atypical benign fibrous histiocytoma.

A case of atypical benign fibrous histiocytoma is reported. A 62-year-old Japanese female visited our clinic because of an asymptomatic solitary lesion on the skin of the left leg. Physical examination revealed a polypoid mass lesion (2.5 x 2.3 x 1.8 cm) with central erosion. The lesion began with a 1 mm-sized papule and slowly enlarged over the 20 years. Clinical diagnosis was a malignant tumor such as dermatofibrosarcoma protuberans, atypical fibroxanthoma or adnexal tumors. Biopsy of the polypoid lesion was carried out. Histopathological examination revealed a polypoid lesion consisting of proliferation of fibroblast-like spindle cells in the dermis. Large atypical cells with pleomorphic nuclei were occasionally observed but mitotic figures were rare. From immunohistochemical results (CD68, Factor-XIII, MIB-1 labeling index), we diagnosed this case as "atypical benign fibrous histiocytoma (ABFH)". Clear distinction has not been made between ABFH, a variant of benign fibrous histiocytoma, and atypical fibroxanthoma, which is a variant of malignant fibrous histiocytoma. Here we report a case of ABFH with a diagnosis of the neoplasm.

Case of exogenous insulin-derived acanthosis nigricans caused by insulin injections.

A 73-year-old male with diabetes mellitus had been treated with insulin for six years. He developed a solid mass on his left lateral of the abdomen at the insulin injection site. A firm subcutaneous mass with dark-red erythema was overlaid by dark-brown keratinized plaques. On histological examination of the mass, keratin proliferation and epidermal papilloma were observed. There were four previously reported cases of acanthosis nigricans that were considered to be caused by continuous injections of insulin. Using immunohistochemistry, in our case the findings were positive in the basal epithelial and prickle cell layers when the patient's lesion was dyed with insulin-like growth factor (IGF)-1 antibody. The coexistence of dermal IGF-1 receptor and acanthosis nigricans found in our patient has not been reported previously, to our knowledge.

Occult neoplastic cells in lymph node sinuses and recurrence/metastasis of stage II/III gastric cancer.

In the present study, we investigated the correlation between the presence of occult neoplastic cells (ONCs) in lymph node sinuses and recurrence/metastasis of stage II/III gastric cancer in 164 patients who underwent radical curative resection. We calculated the five-year relapse-free survival rate (5Y-RFS) and five-year overall survival rate (5Y-OS) of the ONC(+) and ONC(-) groups. The 5Y-RFS was 71.4% in the ONC(-) group and 47.5% in the ONC(+) group (P=0.003). The 5Y-OS was 68.8 and 48.4%, respectively (P=0.008). ONCs were found in 34.8% of stage II patients and were also detected in 66.7% of stage III patients. For distinguishing between the recurrence and non-recurrence groups, the sensitivity of ONC(+) was 64.5% (40/62; P=0.003), the positive predictive value (PPV) was 49.4% (40/81), the specificity was 59.8% (61/102) and the negative predictive value (NPV) was 73.5% (61/83). This high sensitivity indicates that ONC positivity may be a significant indicator for high-risk patients in the early postoperative period, and a lack of ONCs may be a useful indicator for identifying low-risk patients, as patients without ONCs had a high NPV.

Peripheral ameloblastoma of the lower molar gingiva: a case report and immunohistochemical study.

Peripheral ameloblastoma (PA) is a rare extraosseous odontogenic tumor with histological characteristics similar to those of the common intraosseous ameloblastoma. Two questions regarding PA remain: its histogenic origin and how to differentiate between PA and intraoral basal cell carcinoma. We describe a patient with PA. The result of immunohistochemistry showed cytokeratin (CK) 7-, CK14+, CK19+, AE1/AE3+, CAM5.2-, 34 ß E12+, epithelial membrane antigen-, Ber-EP4-, p53-, p63+, and low Ki-67, that was similar to those of 4 cases of intraosseous ameloblastoma. Our results suggest that a PA originates from odontogenic epithelial remnants, rather than from the oral epithelium.

A phlebolith in the anterior portion of the masseter muscle.

The differential diagnosis of a buccal soft tissue mass containing calcified bodies includes a phlebolith associated with a vascular lesion, such as a hemangioma with a calcified intravascular thrombus, and diseases such as sialolithiasis, traumatic myositis ossificans, calcified acne lesion, neoplasm, and calcified lymph nodes, including tuberculosis. The appearance of the calcified bodies on plain radiographs may help to differentiate these entities. Computed tomography, magnetic resonance imaging, and ultrasonography are also useful for differentiating the soft tissue lesions. We report a 17-year-old girl with a small mass containing a calcified body in the anterior portion of the masseter muscle. The mass was resected surgically and evaluated histologically, confirming the diagnosis of phlebolith. We also discuss the differential diagnosis of a buccal soft tissue mass containing calcifications and suggest that the immunolocalization of CD31 at capillaries in the mass may help to diagnose as a phlebolith.

A case of surgically resected lung cancer in a patient with Kartagener's syndrome.

Kartagener's syndrome is a rare inherited disorder with a triology of symptoms (bronchiectasis, sinusitis and situs inversus) and is also associated with abnormalities of the cilia of the respiratory epithelium. Lung cancer arising in Kartagener's syndrome is very rare and to date only 5 cases have been reported in the English and Japanese literature. We report on a case of a 65-year-old Japanese male Kartagener's syndrome patient with squamous cell carcinoma of the lung. A left pneumonectomy was performed and no recurrence was found within 2 years.

Occult neoplastic cells in the lymph node sinuses and recurrence/metastasis of stage III/Dukes' C colorectal cancer.

Lymph nodes from patients with colorectal cancer were immunohistochemically stained for cytokeratin to investigate the relationship between the presence of occult neoplastic cells (ONCs) and recurrence/metastasis. A total of 80 patients with stage III/Dukes' C colorectal cancer were divided into 16 patients who developed recurrence/metastasis (recurrence group) and 64 patients without recurrence (non-recurrence group). ONCs were compared between the two groups with respect to i) single cells (≥ 3 floating ONCs), ii) clusters of cells (1 or more floating aggregates of 2-20 ONCs) and iii) single cells + clusters. When single cells were detected, the sensitivity for recurrence was 87.5% (14/16, p = 0.002), the positive predictive value (PPV) was 32.6% (14/43), the specificity was 54.7% (35/64) and the negative predictive value (NPV) was 94.6% (35/37). For clusters, the sensitivity was 87.5% (14/16, p<0.001), PPV was 41.2% (14/34), specificity was 68.8% (44/64) and NPV 95.7% (44/46). With single cells + clusters, the values were 87.5% (14/16, p<0.001), 48.3% (14/29), 76.6% (49/64) and 96.1% (49/51), respectively. These results suggest that the detection of single cells + clusters is a sensitive indicator of a high risk of recurrence/ metastasis, while ONCs are useful for identifying the low-risk group of patients with stage III colorectal cancer.

Occult neoplastic cells in the lymph node sinuses and recurrence/metastasis of stage II/Dukes' B colorectal cancer.

Lymph nodes from patients with colorectal cancer were immunohistochemically stained for cytokeratin in order to investigate the relationship between the presence of occult neoplastic cells (ONCs) and recurrence/metastasis. A total of 78 patients with stage II/Dukes' B colorectal cancer were divided into two groups. The first group consisted of 18 patients who had developed recurrence/metastasis (recurrence group) and the other one of 60 patients who had survived without recurrence (non-recurrence group). The presence of ONCs was compared between the two groups with respect to i) single cells (≥3 floating ONCs), ii) clusters of cells (≥1 floating aggregates of 2-20 ONCs), and iii) single cells + clusters. When single cells were detected, the sensitivity for recurrence was 55.6% (10/18), the positive predictive value (PPV) was 30.3% (10/33), the specificity was 61.7% (37/60, p=0.195), and the negative predictive value (NPV) was 82.2%(37/45). For the clusters, the sensitivity was 55.6% (10/18), PPV was 37% (10/27), specificity was 71.7% (43/60, p=0.033), and NPV was 84.3% (43/51). With single cells + clusters, the values were 55.6% (10/18), 43.5% (10/23), 78.3% (47/60, p=0.006), and 85.5% (47/55), respectively. These results suggest that the detection of single cells + clusters has a high specificity and NPV, and indicates a low risk of recurrence/metastasis in patients with stage II colorectal cancer.

Surgical resection using retroperitoneal approach for solitary fibrous tumor in the pelvis.

This report concerns a case of solitary fibrous tumor (SFT) for which surgical resection was performed using a retroperitoneal approach. A 41-year-old man was referred to our hospital with urinary retention. Abdominal ultrasound sonography (US) and computed tomography (CT) showed a hypervascular mass lesion in the pelvis. Transrectal biopsy showed SFT. Surgical resection was carried out using a retroperitoneal approach and preserving the neural network related to urinary and erectile functions. Based on immunohistochemical findings, the tumor was diagnosed to be malignant SFT in the pelvic cavity. Urinary function improved post-operation. There was no change to IIEF-5 and it continued to function well. The patient showed no sign of recurrence 12 months after surgery and required no additional therapy.

Anal function-preserving subtotal intersphincteric resection/partial external sphincteric resection with hybrid 2-port hand-assisted laparoscopic surgery (Mukai's operation) for very low stage I rectal cancer: A case report.

A 62-year-old male patient underwent endoscopic mucosal resection (EMR). Additional hybrid 2-port hand-assisted laparoscopic surgery (HALS) (Mukai's operation) was performed for early rectal cancer located at the distal border of the rectum/below the peritoneal reflection (Rb) region [SM massive invasion/ly+/vertical margin (VM)X] via a small transverse incision, approximately 55 mm long, at the superior border of the pubic bone. After the pelvic floor muscles were dissected by laparoscopy-assisted manipulation, transanal subtotal intersphincteric resection (ISR) was performed under direct vision, securing a margin of more than 15 mm distal to the EMR scar. Partial external sphincteric resection (ESR) was also performed to obtain an adequate VM at the posterior region of the EMR scar. After bowel reconstruction, the layers were sutured transanally and a temporary covering colostomy was created. The resected specimen contained no residual tumor cells without lymph node metastasis. At 3 months after the operation, digital examination revealed good tonus of the anal muscles without stricture. The patient is currently undergoing rehabilitation of his anal sphincter muscles in preparation for the colostomy closure. In conclusion, subtotal ISR combined with partial ESR may decrease the need to perform Miles' operation for T1/2 stage I rectal cancer located at the distal border of the Rb region.

Is the T1/2N1 (≤3 nodes) category actually stage IIIA (TNM)/IIIa (Japanese classification) in patients with primary colorectal cancer?

The 5-year relapse-free survival rate (5Y-RFS) and the 5-year overall survival rate (5Y-OS) were calculated for 972 patients (stage I, 206 patients; stage II, 396 patients; stage III, 370 patients). We divided the stage III group into 259 patients with IIIa/N1 disease (≤3 positive nodes) and 111 patients with IIIb/N2 disease (≥4 positive nodes) according to the Japanese classification. The IIIa/N1 and IIIb/N2 categories were each subdivided into T1/2 (stage IIIa, 45 cases; IIIb, 9 cases) and ≥T3 (stage IIIa, 214 cases; IIIb, 102 cases) according to the TNM classification, and 5Y-RFS and 5Y-OS were compared between each subcategory and each group. The 5Y-RFS/5Y-OS values calculated for each stage were as follows: stage I, 94.0/90.7%; stage II, 80.5/81.1%; stage III, 63.5/65.7%. When stage IIIa was compared with IIIb, we obtained 67.9/72.0% for stage IIIa and 53.6% (p=0.001)/50.4% (p<0.001) for stage IIIb. For stage IIIa vs. IIIb in the ≥T3 category, we obtained 63.1/68.5% for stage IIIa and 51.9% (p=0.010)/49.0% (p=0.008) for stage IIIb. For stage IIIa vs. IIIb in the T1/2 category, we obtained 92.1/92.0% for stage IIIa and 72.9% (p=0.040)/63.5% (p=0.003) for stage IIIb. There were significant differences between T1/2 and ≥T3 within stage IIIa (p=0.001/p=0.009), but not within stage IIIb. These results suggest that the T1/2N1 category of colorectal cancer should be classified as a subcategory of stage IB/Ib rather than stage IIIA (TNM)/IIIa (Japanese classification).

Ameloblastic carcinoma, secondary type: a case report.

Malignant variants of ameloblastoma include metastasizing ameloblastoma, which microscopically appears benign but has metastasized and ameloblastic carcinoma that exhibits malignant histopathologic features. Ameloblastic carcinoma is classified into 2 types: a primary odontogenic malignancy and a secondary type resulting from malignant transformation of ameloblastoma. Most secondary ameloblastic carcinomas result from malignant transformation of a primary lesion after repeated postsurgical recurrences. Therefore it is rare to find an untreated secondary type presenting with histologic features of malignant transformation from an earlier benign lesion. We experienced a rare case of ameloblastic carcinoma, secondary type which might arise in an untreated ameloblastoma. The mechanism by which a preexisting benign ameloblastoma goes through a malignant transformation is also described.