Surgical intervention for non-small-cell lung cancer with minimal malignant pleural effusion.

PURPOSE: We assessed the clinical significance of minimal malignant pleural effusion (MPE) using liquid-based cytology (LBC) and immunocytochemistry and reviewed the postoperative outcomes of patients with non-small-cell lung cancer (NSCLC). METHODS: We reviewed 240 patients with cM0 NSCLC who underwent lobectomy. Carcinoembryonic antigen (CEA) immunocytochemistry was performed with LBC to aid in the diagnosis of minimal MPE. We assessed the efficacy of this diagnostic method, relevant clinical factors, and postoperative outcomes. RESULTS: LBC showed positive results in two patients and suspicious results in 21. Of the 21 patients, immunocytochemistry showed minimal MPE in 10 (47.6%); therefore, a total of 12 patients (5%) showed minimal MPE. Minimal MPE is associated with an older age, increased consolidation tumor ratio, and adenocarcinoma histology. The 12 patients with minimal MPE had a 3-year overall survival rate of 90%. Postoperative recurrence was observed in seven patients (58.3%), four of whom were treated with epidermal growth factor receptor-tyrosine kinase inhibitors or immune checkpoint inhibitors, while three are still undergoing treatment, with a survival of 2.2, 2.5 and 5.5 years. CONCLUSIONS: CEA immunocytochemistry offers high sensitivity for the diagnosis of minimal MPE. Surgical intervention may be considered for select patients with NSCLC showing minimal MPE.

A clinicopathologic and molecular analysis of five cases of bronchiolar adenoma with rare mutations.

Bronchiolar adenoma (BA) is a rare benign lung tumor that shows proliferation of bland bronchiolar-type epithelium containing a continuous layer of basal cells. This tumor entity has been newly added to the recent World Health Organization (WHO) classification 5th edition. This entity encompasses a spectrum of lesions: the classic ciliated muconodular papillary tumor (CMPT) and the non-classic CMPT. Although BA is reported to have driver mutations including BRAF V600E, EGFR, and KRAS, the molecular profile of BA is still incompletely understood. Five resected BAs at our institutions were analyzed. The BA lesions were subdivided into two groups: three proximal-type BAs and two distal-type BAs. NRAS codon 12/13 mutation and EML4 exon 20-ALK exon 20 fusion were found in two of the three proximal-types. BRAF V600E mutation was found in one of the two distal-types. Two cases coexisted with lung adenocarcinoma, with EGFR exon 19 deletion and KRAS mutation, respectively. No recurrence was observed at a median of 12 months (range 2-84 months) of follow-up. BA has uncommon variants of mutation seen in lung adenocarcinoma. NRAS mutation and ALK fusion partner has not been reported previously. The present cases may reinforce the distinctive biology of BA from lung adenocarcinoma.

Oncocytic variant, a novel subtype of chromophobe renal cell carcinoma: a report of two cases and a literature review.

A novel variant of chromophobe renal cell carcinoma showing an oncocytic phenotype is proposed. Two new cases of this rare entity are presented and discussed along with six previous cases from our colleagues. A 76-year-old man and a 78-year-old man had a 3.4-cm and a 3.2-cm-diameter renal mass, respectively. On histopathological examination of surgical specimens, uniform eosinophilic cuboidal cells without a perinuclear halo growing in a tubular pattern were seen, and differential diagnosis from oncocytoma was necessary. Immunohistochemical staining for cytokeratin 7 and E-cadherin showed diffusely positive patterns in both, as in the previous reports. Although monosomy of chromosomes 7, 10, 13, and 17 was commonly observed in the previous reports, gains of chromosome 19 were observed in the two present cases. Immunohistochemical and cytogenetic approaches lead to exclusion of oncocytoma and the diagnosis of an oncocytic variant of chromophobe renal cell carcinoma.

Suppressive Effects of Aspirin for Postthoracotomy Pleural Adhesion in Rats.

BACKGROUND: Postoperative adhesion is one of major concerns at re-thoracotomy. Aspirin has both the anti-platelet and anti-inflammatory effects, and decreases several cytokines production. OBJECTIVE: We investigated that aspirin could reduce postoperative adhesion formation in a rat model. METHODS: We cauterised the lung visceral pleural to make postoperative adhesion in rats. The animals were allocated to a control group and an aspirin administration group (100 mg/kg/day for 14 days). We performed re-thoracotomy and evaluated the adhesion lengths on day 14. We also investigated the cytokine expression in the adhesion region and the peripheral tissue with platelet-derived growth factor (PDGF), platelet-derived growth factor receptor (PDGFR), alpha smooth muscle actin (α-SMA), transforming growth factor beta 1 (TGF-ß1), and vascular endothelial growth factor-A (VEGF-A), sequentially. RESULTS: The adhesion lengths were significantly shorter in the aspirin group than that in the control group (8.7±2.0 mm vs 11.2±1.1 mm, p=0.024). The expressions of PDGF and PDGFR were lower in the aspirin group than that in the control group on day 3. The expression of α-SMA on fibroblasts decreased in the aspirin group on day 3. There was no significant difference in the expressions of TGF-ß1 and VEGF-A with administration of aspirin. CONCLUSIONS: Aspirin could reduce postoperative pleural adhesion by inhibiting the expression of PDGF.

Chromophobe renal cell carcinoma, oncocytic variant: Cytological and ultrastructural observations.

There is only one report on cytological findings of oncocytic variant of chromophobe renal cell carcinoma (RCC). In this article, we report a new case with focus on cytological, and ultrastructural findings. A 60-year-old Japanese man was found to have a right renal tumor on medical checkup. In imprint cytological materials, the smears consisted of slightly discohesive clusters and isolated tumor cells with granular green colored cytoplasm on Papanicolaou staining. Nuclei were generally round and centrally located in the cytoplasm, but nuclear irregularity or perinuclear halo was absent. Ultrastructurally, the tumor was full of mitochondria with tubulovesicular cristae. Fluorescence in situ hybridization study using histological material showed multiple chromosomal losses including chromosomes 7, 10, 13, and 17. This finding supports the hypothesis that this variant may ultrastructurally show the nature of chromophobe RCC rather than renal oncocytoma.

Chromophobe renal cell carcinoma, oncocytic variant: a proposal of a new variant giving a critical diagnostic pitfall in diagnosing renal oncocytic tumors.

In chromophobe renal cell carcinoma (RCC), two forms of typical and eosinophilic variants have been reported to date. We have previously reported a new variant of chromophobe RCC, namely an oncocytic variant. However, little is known on the histological features of this variant. In this article, we report such five cases. Macroscopically, the tumor was well demarcated, but unencapsulated. The cut surface of the tumor showed brown in color, but neither hemorrhage nor necrosis was seen. Microscopically, the tumor consisted of predominant tubular configuration with or without various proportion of solid-sheet pattern. In one tumor, tumor cells microscopically invaded branches of renal vein. In addition, the constituting cells were characterized by the oncocytic cytoplasm, trivial to minimal variation in tumor size, indistinct to slightly distinct cell border, centrally located round nuclei and the absence of perinuclear halo. These characteristics entirely resembled renal oncocytoma. However, neoplastic cells immunohistochemically showed the diffuse and strong labeling for cytokeratin 7 and mitochondrial antigen in all cases. In addition, in fluorescence in situ hybridization (FISH) study the loss of more than four chromosomes among chromosomes 7, 10, 13, 17 and 21 was confirmed in all tumors and the diagnosis of chromophobe RCC was rendered. In conclusion, we propose a new variant, namely an oncocytic variant, of chromophobe RCC morphologically resembling renal oncocytoma and biologically showing characteristics of chromophobe RCC, and this recognition is practically crucial in the differential diagnosis from renal oncocytoma.

Utility of immunohistochemical analysis of KAI1, epithelial-specific antigen, and epithelial-related antigen for distinction of chromophobe renal cell carcinoma, an eosinophilic variant from renal oncocytoma.

Distinction of renal oncocytoma (RO) from chromophobe renal cell carcinoma (ChRCC) is important because their clinical behavior is different. As part of a search for the best available immunohistochemical markers to distinguish ChRCC from RO, we investigated the immunohistochemical profiles of these tumors. We selected 30 renal tumors consisting of ChRCC, typical variant (n = 14), ChRCC, eosinophilic variant (n = 6), and RO (n = 10). Their expression of cytokeratin (CK) 7, KAI1, epithelial-specific antigen (ESA), epithelial-related antigen (ERA), Claudin- 7, and Claudin-8 was studied using an autostainer. Immunoreactivity was assessed based on a combined score of the extent and intensity of staining. Compared to RO, a significantly higher percentage of the total ChRCCs stained positive for CK7 (85% vs. 10%, respectively), KAI1 (90% vs. 10%), ESA (95% vs. 10%), ERA (95% vs. 10%), and Claudin-7 (95% vs. 20%) (P < 0.001). Additionally, there was a significant difference between the percentage of ChRCC eosinophilic variant (ChRCC-E) and RO that stained positive for KAI1 (100% vs. 10%, respectively), ESA (83% vs. 10%), and ERA (83% vs. 10%) (P < 0.001). We recommend immunohistochemical analysis of KAI1, ESA, and ERA to distinguish ChRCC-E from RO.

Immunohistochemical application of S100A1 in renal oncocytoma, oncocytic papillary renal cell carcinoma, and two variants of chromophobe renal cell carcinoma.

S100A1 is a calcium-binding protein and a member of the S100 family. Recently, S100A1 immunohistochemistry may be an available marker in the differential diagnosis between renal oncocytoma and chromophobe renal cell carcinoma (RCC). However, there are no reports on S100A1 expression in oncocytic papillary RCC that has been recently identified. In this article, we immunohistochemically examined the expression of S100A1 protein in 18 renal tumors including 4 renal oncocytoma, 10 chromophobe RCCs, and 4 oncocytic papillary RCCs. All the cases of renal oncocytoma and oncocytic papillary RCC showed a positive reaction for S100A1 with cytoplasmic pattern. In chromophobe RCC, 3 of 4 tumors with typical variant and 4 of 6 tumors in eosinophilic variant were completely negative for S100A1. Finally, S100A1 immunohistochemistry may be useful in distinguishing renal oncocytoma from chromophobe RCC, but it may be of no use in the differential diagnosis between renal oncocytoma and oncocytic papillary RCC.

Diagnostic pitfall on the histological spectrum of adult-onset renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion recently has been found. In this article, we demonstrate an unusual features of such a case. A 73-year-old Japanese woman presented with macroscopic hematuria. The imaging examinations disclosed the renal tumor. Histological examination showed the finding of ASPL-TFE3 RCC, which was characterized by papillary, alveolar, or solid growth of voluminous cell with clear and eosinophilic cells, and stromal psammoma body and hyaline nodules. Additionally, shrunken nuclei, thick cell border, and perinuclear clearing characteristic of chromophobe renal cell carcinoma were observed in the alveolar growth area and the transitional zone between stromal hyalinization, and osseous metaplasia was identified. Immunohistochemically, nuclei of tumorous cell were diffusely positive for TFE3. A RT-PCR study revealed the ASPL-TFE3 chimeric transcript. Finally, pathologists should recognize that the histology of RCC associated with Xp11.2 translocation/TFE3 gene fusion may focally resemble that of chromophobe RCC, but TFE3 immunohistochemistry and molecular genetic study may be helpful in the differential diagnosis. Moreover, osseous metaplasia as well as psammoma bodies should be added to the histological spectrum of the stromal change in RCC associated with Xp11.2 translocations/TFE3 gene fusions.

Imprint cytologic features of chromophobe renal cell carcinoma morphologically resembling renal oncocytoma: is this an oncocytic variant of chromophobe renal cell carcinoma?

In this article, we report a case of 76-year-old woman with a rare variant of chromophobe renal cell carcinoma (CRCC). Cytologically, renal tumor cells obtained from imprint cytology were isolated or arranged in small or monotonous population cells with abundant granular cytoplasm. Neoplastic cells showed regular and uniformly shaped small round to oval nuclei with smooth margin. Binucleation was occasionally seen. Immunocytochemically, the cytoplasm of almost all tumor cells was diffusely positive for vimentin and CK 7. Histologically, the cytoplasm was abundant granular eosinophilic and composed of solid cell sheets or pseudoacinar structures. Additionally, tumor cells showed infiltration into some small renal veins covered by a single layer of endothelial cells. These cytological and histological features entirely resembled those of renal oncocytoma. We performed the analysis of von Hippel-Lindau (VHL) gene mutation, 3p loss of heterozygosity (LOH), and fluorescence in situ hybridization (FISH) on chromosomes 7, 10, 13, 17, and 21. As a result, we confirmed monosomy of chromosomes 7, 10, 13, and 17, and these findings corresponded to the diagnosis of CRCC. Finally, we present a case of renal tumor morphologically resembling renal oncocytoma but genetically showing CRCC. We suggest that oncocytic variant of CRCC may actually exist.

Imprint cytologic features in renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion in an adult: a case report.

BACKGROUND: Adult-onset renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion is a very rare tumor. To date, there are no reports on immunocytochemical study of the primary tumor. We describe such a case that we diagnosed by immunocytochemistry of imprint cytology material. CASE: A 46-year-old man was found to have a mass in the lower pole of the right kidney. Magnetic resonance imaging (MRI) T2-weighted images showed a hypointense area in the tumor, and papillary RCC was suspected. Imprint cytology showed tumor cells that were isolated or arranged in large or small papillary clusters. Irregularly shaped large oval nuclei, finely granular chromatin and a single large nucleolus were noted. Cytoplasm was abundant and admixed with clear and granular eosinophilic patterns and scattered large vacuolated cells. Almost all tumor cells diffusely expressed immunocytochemical reactivity to TFE3 protein. Hyaline nodules were observed in the stroma. Ultrastructurally, neoplastic cells contained rhomboid crystals identical to those of alveolar soft part sarcoma. CONCLUSION: The immunocytochemistry of TFE3 protein may be a powerful tool for accurate diagnosis when RCC associated with Xp11.2 translocation/TFE3 gene fusion is suspected by imprint cytology even in adult-onset cases, and cytotechnologists should accurately recognize cytologic findings of this tumor.

Chromophobe renal cell carcinoma: useful diagnostic application of imprint cytology and fluorescence in situ hybridization of chromosomes 10 and 21 in two cases of typical and eosinophilic variants.

Chromophobe renal cell carcinoma (RCC) is subdivided into typical and eosinophilic variants. We report such two cases with focus on imprint cytology and fluorescence in situ hybridization (FISH). The first case is a 53-year-old Japanese man and the second is a 76-year-old Japanese man. Histologically, the diagnosis of typical and eosinophilic variants of chromophobe RCC was suspected. In imprint cytology, irregularity of nuclear membrane, binucleation, perinuclear halo, and thick cell border were observed. Immunohistochemically, neoplastic cells of both tumors were positive for cytokeratin 7, E-cadherin, c-kit, and CD10. In FISH study, both tumors revealed the monosomy of chromosomes 10 and 21. Additionally, FISH study in eosinophilic variant of chromophobe RCC showed the disomy of chromosomes 7 and 17. In conclusion, we suggest that the combination study of imprint cytology and FISH of chromosomes 10 and 21 as well as routine histology may contribute to the accurate diagnosis of chromophobe RCC.

Paranuclear blue inclusions of small cell carcinoma of the stomach: report of a case with cytologic presentation in peritoneal washings.

BACKGROUND: Primary gastric small cell carcinoma is a rare but important entity. We describe a case that we diagnosed by peritoneal washing cytology. CASE: A 70-year-old male presented with upper abdominal discomfort and underwent endoscopic evaluation. Gastric endoscopy revealed a diffuse, infiltrating tumor from the body to the antrum. Total gastrectomy with lymph node dissection and intraoperative peritoneal washing cytology were carried out. Peritoneal washing cytology showed the presence of many undifferentiated malignant small cells with a necrotic background. The tumor cells were small and round, with naked, hyperchromatic nuclei and finely granular chromatin. Some tumor cells contained paranuclear blue inclusions (PBls) in the cytoplasm. The tumor cells were positive for neuron-specific enolase and synaptophysin on immunocyto-chemistry. Carcinoembryonic antigen, alpha-fetoprotein (AFP) and leukocyte common antigen were negative. Pathologic diagnosis after the operation was moderately to poorly differentiated adenocarcinoma and small cell carcinoma containing AFP-positive cells. CONCLUSION: The prognosis of primary gastric small cell carcinoma is usually poor. Our patient died of multiple liver metastases and peritonitis carcinomatosa 69 days after surgery. When a gastric small cell carcinoma is suspected in peritoneal washings, immunocytochemical demonstration of neuroendocrine differentiation is required to arrive at the final diagnosis.

A case of solid variant type of pancreatic serous cystadenoma mimicking islet cell tumor.

We report a case of the solid variant type of pancreatic serous cystadenoma in which the very small size of the cyst on ultrasonography and computed tomography made distinguishing this tumor from other hypervascular solid tumors difficult. Recognizing the imaging features of high signal intensity on heavily T2-weighted image on MR may be helpful for correctly diagnosing the solid variant type of pancreatic serous cystadenoma.

Leiomyomatosis peritonealis disseminata with malignant change in a man.

Leiomyomatosis peritonealis disseminata (LPD) is a rare clinicopathological entity typically observed in women of reproductive age. We report a case of LPD with malignant change in a man. A 77-year-old man presented with a mass measuring 10 cm in diameter at the terminal ileum and numerous peritoneal small nodules that were revealed by abdominal computed tomography. Right hemicolectomy with lymph node dissection was performed. Macroscopically, a tumor of the terminal ileum consisted of aggregates of small nodular lesions with calcification and necrosis. The wall of the ileum and colon was intact. Microscopically, some of the nodular lesions consisted of neoplastic growths of atypical spindle cells with cellular atypism and abnormal mitoses. A few of these lesions were completely surrounded by smooth muscle bundles. Hemorrhages and necroses were found within the tumor nodules. Immunohistochemically, the tumor cells were positive for vimentin, desmin, muscle actin, alpha-smooth muscle actin, cytokeratin and p53. The remaining nodular lesions, including small peritoneal lesions, were composed of hypocellular hyalinizing nodules. This case was thought to be LPD with malignant change, although the pathogenesis was uncertain because the tumor cells were negative for estrogen and progesterone receptors.

Primary pulmonary leiomyosarcoma. Report of a case diagnosed by fine needle aspiration cytology.

BACKGROUND: Primary pulmonary leiomyosarcoma is a rare but important entity. We report a case diagnosed by fine needle aspiration cytology. CASE: A 73-year-old male presented with an asymptomatic, right, pulmonary, subpleural nodule detected by computed tomography during follow-up for chronic obstructive pulmonary disease. Fine needle aspiration cytology showed cellular smears with numerous single or loosely cohesive groups of spindle-shaped to round cells. The tumor cell nuclei were blunt ended (cigar shaped), with fine to fine-granular chromatin, prominent nucleoli and an irregular nuclear rim. The tumor cells were positive for desmin and negative for cytokeratin and S-100 protein by immunocytochemistry. Right upper lobectomy with lymph node dissection was performed. Pathologic diagnosis after microscopic, immunohistochemical and electron microscopic studies was leiomyosarcoma. CONCLUSION: To our knowledge, this is the first reported case of primary pulmonary leiomyosarcoma arising in the subpleural region diagnosed by fine needle aspiration cytology. Immunocytochemistry was useful in establishing the diagnosis in this case.