Mucinous micropapillary pattern in lung adenocarcinomas: a unique histology with genetic correlates.

AIMS: In lung adenocarcinoma (ADC), micropapillary carcinomas (MPCs) are associated with poor prognosis because these tumours exhibit higher metastatic potential. Despite this, there are no studies investigating the differences between mucinous and non-mucinous MPC. METHODS AND RESULTS: We evaluated the proportion of micropapillary components in lung ADCs, and compared the differences with respect to the presence or absence of associated mucin. Tumour specimens from 694 patients with consecutively resected primary lung ADC were reviewed, and 37 cases of invasive mucinous ADCs were excluded. A significant (≥5%) micropapillary component was noted in 320 (48.7%) of 657 evaluable cases. When the cases with micropapillary component were divided into 67 (20.9%) mucinous and 253 (79.1%) non-mucinous subtypes, tumours with mucinous micropapillary component exhibited significantly more aggressive pathological features, a higher proportion of HER2 mutations (P = 0.002) and ALK rearrangements (P < 0.001), and a lower proportion of EGFR mutations (P = 0.038) compared to those with a non-mucinous micropapillary component. In survival analyses, mucinous MPC tended to be more aggressive compared with non-mucinous MPC, but its prognostic value was not statistically significant (P = 0.076). CONCLUSIONS: Mucinous micropapillary pattern is an under-recognized unique growth associated significantly with HER2 mutation and ALK rearrangement.

Solitary fibrous tumor of the pleura: morphogenesis and progression. A report of 36 cases.

PURPOSE: We attempted to identify the exact point of tumor eruption of a solitary fibrous tumor of the pleura (SFTP). METHODS: We morphologically classified 36 SFTPs into 5 categories. Type A showed a connection that included a bloodstream with the pleura on both sides. Type B only showed a connection that included a bloodstream with the visceral pleura, and had a non-bloodstream connection with the parietal pleura. Type C only showed a connection that included a bloodstream with the visceral pleura, and had no connection with the parietal pleura. Type D showed a non-bloodstream connection with the visceral pleura, and only showed a connection that included a bloodstream with the parietal pleura. Finally, type E had no connection with the visceral pleura, and only showed a connection that included a bloodstream with the parietal pleura. The clinicopathological profiles of the tumors were investigated according to their type. RESULTS: The distribution of the 36 SFTPs was as follows: A (19 %), B (6 %), C (67 %), D (0 %) and E (8 %). The tumors categorized as type A tended to be large in size. CONCLUSIONS: SFTPs commonly arise from the visceral pleura and in accordance with tumor progression they will form a non-bloodstream connection with the parietal pleura. Finally, a vascular pedicle will arise with the parietal pleura.

Frequent BRAF or EGFR Mutations in Ciliated Muconodular Papillary Tumors of the Lung.

INTRODUCTION: Ciliated muconodular papillary tumors (CMPTs) are recently characterized, rare peripheral nodules of the lung. These small tumors are histologically comprised of a vaguely organized mixture of nonatypical ciliated columnar cells, mucous cells, and basal cells, and consistently follow a benign clinical course. However, the histogenesis of CMPTs remains uncertain. METHODS: We performed detailed genomic analyses of 10 archived CMPT cases, using next-generation sequencing and high-resolution melting analysis. RESULTS: Mutations were identified in eight of the 10 cases (80%); four cases harbored the BRAF-V600E mutation, one case harbored the BRAF-G606R mutation, and three cases harbored deletions in exon 19 of EGFR. All of the deletions in EGFR were of the E746-T751/S752V subtype. CONCLUSIONS: The high prevalence of driver gene mutations in CMPTs supports the notion that these lesions are neoplastic rather than reactive or metaplastic.

Myocardial Sleeve Tissues in Surgical Lung Specimens.

Left atrial myocardial extensions over the pulmonary veins (PVs), known as myocardial sleeves, are present in the physiological anatomy of most individuals. Although this structure has recently received clinical attention as a major origin of paroxysmal atrial fibrillation (AF), it has not been documented in surgical specimens. Here, we examine incidentally identified myocardial sleeve tissue in routinely processed lung resection specimens to determine its incidence and diagnostic implications. Among 694 lung resection specimens with evaluable PV margins, myocardial sleeve tissue was identified in 26 cases (3.7%). The tissue was located within the adventitia of the PVs, mostly in margin preparations, and existed outside the pericardium in the majority of cases. Carcinoma infiltration of the sleeves was evident in 6 cases. No heart injuries were observed, and no tumors invaded the heart. Preoperative electrocardiography showed sinus rhythm in all cases, whereas postoperative monitoring revealed sinus rhythm in all patients except one who showed AF and flutter. Myocardial sleeve tissue is an underrecognized incidental finding in lung resection specimens, and it is not indicative of heart injury. Cancer infiltration into this tissue indicates neither heart invasion nor, by itself, invasion into the pericardium. Although surgical transection of the myocardial sleeve did not evoke immediate arrhythmia in most cases, the overall influence of this procedure on the postsurgical risk of AF remains to be determined in further studies involving extensive rhythm assessment.

Ciliated muconodular papillary tumors of the lung: a clinicopathologic analysis of 10 cases.

Ciliated muconodular papillary tumors (CMPTs) are rare peripheral nodules of the lung first described in 2002. Because of their rarity and nonstandardized diagnostic terminology, CMPTs have been poorly recognized among pathologists. To better characterize these lesions, we undertook a detailed clinicopathologic and immunohistochemical study of 10 archival cases. Ten CMPTs occurred in 7 men and 3 women with a median age of 62 years. All were small peripheral nonendobronchial nodules with a mean diameter of 1.0 cm. All but 1 tumor were incidentally detected by computed tomography-based screening, all of which were radiologically interpreted as adenocarcinomas. Although limited surgery treated all but 1 CMPT, they followed a benign course with no recurrence at a mean follow-up of 43 months (range: 2 to 88 mo). Histologically, CMPTs showed glandular and/or papillary architecture, comprising a vaguely organized mixture of nonatypical ciliated columnar cells, mucous cells, and basal cells, often enveloped by copious intra-alveolar mucin. Micropapillary tufts of ciliated cells and seemingly discontinuous growth along alveolar walls were occasionally present, mimicking adenocarcinomas. Ciliated cells and basal cells were immunopositive for TTF-1 and p40, respectively, whereas mucous cells lacked HNF4α expression. CMPTs are rare, likely benign, underrecognized processes of the lung that should be distinguished from adenocarcinomas.

Localized gastric amyloidosis differentiated histologically from scirrhous gastric cancer using endoscopic mucosal resection: a case report.

INTRODUCTION: Amyloidosis most often manifests as a systemic involvement of multiple tissues and organs, and an amyloidal deposit confined to the stomach is extremely rare. It is sometimes difficult to provide a definitive diagnosis of localized gastric amyloidosis by biopsy specimen and diagnosis of amyloidosis in some cases has been finalized only after surgical resection of the stomach. CASE PRESENTATION: A 76-year-old Japanese woman with epigastric discomfort underwent an esophagogastroduodenoscopy procedure. The esophagogastroduodenoscopy revealed gastric wall thickening, suggesting scirrhous gastric carcinoma, at the greater curvature from the upper to the lower part of the gastric corpus. A biopsy specimen revealed amyloid deposits in the submucosal layer with no malignant findings. We resected a representative portion of the lesion by endoscopic mucosal resection using the strip biopsy method to obtain sufficient tissue specimens, and then conducted a detailed histological evaluation of the samples. The resected specimens revealed deposition of amyloidal materials in the gastric mucosa and submucosa without any malignant findings. Congo red staining results were positive for amyloidal protein and exhibited green birefringence under polarized light. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL) amyloid protein type. Based on these results, gastric malignancy, systemic amyloidosis and amyloid deposits induced by inflammatory disease were excluded and this lesion was consequently diagnosed as localized gastric amyloidosis. Our patient was an older woman and there were no findings relative to an increase in gastrointestinal symptoms or anemia, so no further treatment was performed. She continued to be in good condition without any finding of disease progression six years after verification of our diagnosis. CONCLUSIONS: We report an unusual case of primary amyloidosis of the stomach resembling scirrhous gastric carcinoma. This case of localized gastric amyloidosis was differentiated from scirrhous gastric cancer after performing endoscopic mucosal resection without an invasive surgical resection, as endoscopic mucosal resection provided sufficient tissue specimens from the lesion to make an accurate histological evaluation.