Sublobar resection for lung adenocarcinoma less than 2 cm containing solid or micropapillary components radiologically presented as consolidation-to-tumor ratio (CTR) ≤0.25 [ground-glass opacity (GGO)].

Background: The suitability of sublobar resection as a surgical approach for early-stage non-small cell lung cancer (NSCLC) remains unclear. This study investigated the feasibility of sublobar resection in patients with pathological-stage IA adenocarcinoma less than 2 cm characterized by a high-risk pathological subtype but exhibiting radiologically noninvasive features. Methods: We conducted a retrospective review of patients diagnosed with pathological stage IA lung adenocarcinoma who underwent surgical intervention between 2013 and 2017. The inclusion criteria included a maximum tumor diameter of 2.0 cm or less, a consolidation-to-tumor ratio (CTR) of 0.25 or less, and a histopathological confirmation of a solid or micropapillary component. Patients were categorized into sublobar resection and lobectomy groups, and propensity score matching was employed to mitigate potential confounders. The primary endpoints were lung cancer-specific survival (LCSS) and overall survival (OS). Results: The study comprised 149 patients, with 84 in the lobectomy group and 65 in the limited resection group. In the overall cohort, the 5-year LCSS was 100% for both groups, while the 5-year OS was 97.6% (95% CI: 94.41-100.00%) in the lobectomy group and 100% in the sublobar resection group (P=0.21). After propensity score matching, the LCSS remained at 100% for both groups, and the 5-year OS was 97.14% in the lobectomy group and 100% in the sublobar resection group (P=0.32). Conclusions: Based on our experience, for lung adenocarcinoma containing solid/micropapillary subtype, a size less than 2 cm, and a CTR ≤0.25, the oncological outcomes appeared to be comparable between sublobar resection and lobectomy, suggesting that sublobar resection might serve as an equivalent alternative to lobectomy for such lesions.

Unusual Presentation of Adenoid Cystic Carcinoma of the Tongue: A Case Report and Review of the Literature.

Adenoid cystic carcinoma (ACC) is a rare malignant tumor that affects the salivary glands. Its notable characteristics include aggressive local growth, infiltration of nerves (perineural invasion), a propensity to disseminate to other parts of the body (metastasize), and a high likelihood of recurrence. Here, we present the case of a 71-year-old male patient who presented with swelling on the posterior left side of his tongue, which had been causing him difficulty in chewing for the past six months. The parotid gland is frequently impacted in the head and neck area, with the tongue being comparatively uncommon. While distant metastasis is frequent, metastasis to nearby lymph nodes is not as common. However, if it does occur, it is associated with a poor prognosis and reduces the average survival age of the patient. The preferred treatment for ACC is surgical removal with wide resected margins. If it metastasizes to lymph nodes, then adjunct therapy is the treatment modality for the lesion. ACC exhibits three histopathological patterns: solid, tubular, and cribriform. The solid type is associated with a poorer prognosis compared to cribriform type, which typically has a better prognosis. This case, occurring on the tongue, is rare.

Micropapillary and solid components as high-grade patterns in IASLC grading system of lung adenocarcinoma: Clinical implications and management.

OBJECTIVES: The grading system proposed by the International Association for the Study of Lung Cancer is based on a combination of predominant histologic subtypes and the proportion of high-grade components with a cutoff of 20%. We aimed to examine the clinical implications of the grading system beyond the discrimination of patient prognosis, while assessing the biological differences among high-grade subtypes. METHODS: We retrospectively reviewed 648 consecutive patients with resected lung adenocarcinomas and examined their clinicopathologic, genotypic, and immunophenotypic features and treatment outcomes. Besides the differences among grades, the clinical impact of different high-grade components: micropapillary (MIP) and solid (SOL) patterns, was individually evaluated. RESULTS: Survival outcomes were well-stratified according to the grading system. Grade 3 tumors exhibited aggressive clinicopathologic features, while being an independent prognostic factor in multivariable analysis. A small proportion (<20 %) of high-grade components in grade 2 had a negative prognostic impact. The prognostic difference bordering on the 20 % cutoff of the MIP proportion was validated; however, the proportion of SOL component did not affect prognosis. A survival benefit from adjuvant chemotherapy was observed in grade 3 tumors regardless of histologic subtype, but not in grade 1-2 tumors. The molecular and immunophenotypic features were different among grades, but still heterogeneous in grade 3, with MIP harboring frequent EGFR mutation and SOL exhibiting high PD-L1 expression. The treatment outcome after recurrence was worse in grade 3, but tumors with MIP pattern had an equivalent prognosis to that of grade 1-2 tumors, reflecting the high frequency of molecular targeted therapy. CONCLUSIONS: In addition to stratifying patient prognosis, the current grading system could discriminate clinical course, therapeutic effects of adjuvant chemotherapy, and molecular and immunophenotypic features. Further stratification based on biological heterogeneity in grade 3 remains necessary to enhance the role of the grading system in guiding patient management.

Lung adenocarcinoma with micropapillary and solid patterns: Recurrence rate and trends.

BACKGROUND: Lung adenocarcinomas with micropapillary pattern (MP) or solid pattern (SP) have poor prognosis with frequent postoperative recurrence. However, treatment strategies for these histological subtypes have not been established. This study examined the recurrence rates and patterns in patients with these histological subtypes. METHODS: Overall, 238 patients with lung adenocarcinoma who underwent radical resection were included. According to the histological subtypes, the patients were classified into three groups: neither MP nor SP (MP-/SP-), MP (MP+), and SP (SP+). The clinical and pathological characteristics and recurrence-free survival (RFS) were examined in each group. In addition, univariate and multivariate analyses were performed to investigate the recurrence factors. The site of recurrence, PD-L1 expression, and driver mutations were examined in patients with postoperative recurrence. RESULTS: The recurrence rates were significantly higher in the MP+ and SP+ groups (p = 0.01). The RFS was significantly shorter in the MP+ and SP+ groups (p < 0.001) than in the MP-/SP- group, especially in pStage 1A (p = 0.001). The relationship between recurrence and pathologic factors was significant for pleural, lymphatic, and vascular invasion, as well as MP in univariate analysis and only for MP in multivariate analysis. Most recurrences were distant metastases in the MP+ and SP+ groups. PD-L1 was highly expressed in recurrent SP+ cases. CONCLUSIONS: Early-stage lung adenocarcinoma with MP or SP frequently has postoperative recurrence. Prevention of distant metastases is important in these patients to improve prognosis, and aggressive postoperative chemotherapy may be considered.

Papillary thyroid carcinoma with aggressive fused follicular and solid growth pattern: A unique histological subtype with high-grade malignancy?

Papillary thyroid carcinoma (PTC) is usually indolent; however, some rare subtypes of PTCs, such as columnar cell and hobnail subtypes, carry poor prognosis as an intermediate malignancy between differentiated carcinoma and anaplastic carcinoma. We present the case of a 56-year-old Japanese woman having PTC with aggressive behavior showing characteristic histological features of a predominantly fused follicular and focally solid (FFS) pattern. The fused follicular pattern is cribriform-like without intermingled vessels. This PTC with FFS pattern included frequent mitotic figures, necrosis, lymphovascular invasion, and metastases with high clinical stage. The tumor cells were broadly positive for antibodies to TTF-1, PAX8, and bcl-2, and negative for cyclin D1. Ki-67 labeling index was approximately 10%, and there was occasional positivity of p53. Targeted next generation sequencing analysis only detected a NRAS mutation (Q61K); there was no mutation and no translocation of other genes including BRAF and RET/PTC. To our knowledge, this is first report that PTC shows aggressive FFS growth pattern. The tumor is possibly included in the new category of differentiated high-grade thyroid carcinoma in the World Health Organization 2022 classification, or in a novel subtype of PTC owing to its characteristic histological feature and intermediate malignancy between differentiated carcinoma and anaplastic carcinoma.

Clínica, epidemiología e imagenología del quiste óseo aneurismático en el territorio craneofacial, análisis de sus patrones histopatólogicos: revisión narrativa / Clinical, epidemiology and imaging of the aneurysmal bone cyst in the craniofacial territory, analysis of its histopathological patterns: a narrative review

Introducción: El quiste óseo aneurismático (QOA) tiene una diversidad de características clínicase imagenológicas. Existe poca información respecto a la posible relación entre algunas de estas características y los patrones histopatológicos del QOA. El propósito de la presente revisión fue analizar la clínica, epidemiología e imagenología de casos de QOA, y determinar qué características podrían tener relación con algún tipo de patrón histopatológico del QOA en el territorio craneofacial. Materiales y métodos:Se realizó una búsqueda de casos de QOA en el territorio craneofacial publicados desde el año 2000, en PubMed, Scopus y Web of Science, mediante la búsqueda ("Aneurysmal bone cyst") AND ("Skull" OR "Jaw" OR "Mandible" OR "Maxilla"). Los casos debían tener información histopatológica, clínica, epidemiológica e imagenológica. Revisión: Se incluyó 40 artículos con 41 lesiones, siendo 34 de patrón clásico y 7 de patrón mixto-sólido (M-S). El patrón M-S se presentó mayoritariamente sin dolor y en el sexo masculino, mientras que el patrón clásico con dolor asociado y en el sexo femenino. Respecto a la imagenología, el patrón M-S se presentó sin límites definidos-corticalizados y generó perforación ósea con mayor frecuencia que el patrón clásico. Conclusiones: Los patrones histopatológicos del QOA tienen características clínicas, epidemiológicas e imagenológicas similares. Sin embargo, difieren en sexo, dolor asociado, límites definidos corticalizados y perforación ósea, lo que permitiría orientar al diagnóstico hacia un patrón histopatológico. (AU)

Introduction: The aneurysmal bone cyst (ABC) has a variety of clinical and imaging characteristics. There is little information regarding the possible relationship between some of these characteristics and its histopathological patterns. The aim of this review was to analyze the clinical, epidemiology and imaging characteristics of ABC cases, and determine what characteristics might be related to some type of histopathological pattern of ABC in the craniofacial territory. Materials and methods: A search was conducted for ABC cases in the craniofacial territory published since 2000, on PubMed, Scopus and Web of Science, by searching ("Aneurysmal bone cyst") AND ("Skull" OR "Jaw" OR "Mandible" OR "Maxilla"). Cases had to have histopathological, clinical, epidemiological, and imaging information. Review: 40 articles with 41 ABC lesions were included, with 34 being classic pattern and 7 mixed-solid (M-S). The M-S pattern was mostly painless and in males, while the classic pattern, with associated pain was mostly in females. Regarding imaging, the M-S pattern was without defined-corticated limits and with bone perforation more frequently than the classic pattern. Conclusions: Histopathological patterns of ABC have similar clinical, epidemiological and imaging characteristics. However, they differ in sex, associated pain, defined-corticated limits and bone perforation, which would allow the diagnosis to be directed towards a specific histopathological pattern. (AU)

Prognostic significance of micropapillary and solid patterns in stage IA lung adenocarcinoma.

OBJECTIVE: To evaluate the value of the non-predominant micropapillary and solid patterns in prognosis of lung adenocarcinoma. METHODS: Totally 422 patients diagnosed with stage IA lung adenocarcinomas were included, and all their slides were reviewed. We compared clinicopathological characteristics and survival outcomes between MP- & SD- (both micropapillary and solid component were absent), MP+/SD+ (either micropapillary or solid component was present, but the single or combined percentage of the MP and SD was not greater than 50%) and MPp/SDp (either micropapillary or solid or the combined percentage of these two components was great than 50%). RESULTS: Patients with MP- & SD- had smaller tumor size (P=0.012) and lower spread through air spaces rates (P<0.001). Patients with MP- & SD- had significantly better 5-year recurrence free survival than MP+/SD+ (91% versus 70%, P<0.001) and MPp/SDp (91% versus 56%, P<0.001). The difference of RFS between MP+/SD+ subgroup and MPp/SDp subgroup was not significant (P=0.177). In the multivariate analysis, patients with MP- & SD- had a better recurrence free survival than the other two groups (versus: MP+/SD+, HR, 3.198; 95% CI, 1.537-6.653; P=0.002; versus MPp/SDp: HR, 4.981; 95% CI, 2.266-10.950; P<0.001). CONCLUSIONS: The presence of micropapillary or solid patterns, even not predominant, was a risk factor for predicting poor recurrence free survival in very early stage lung adenocarcinoma.

Histopathological typing in diffuse malignant epithelioid mesothelioma: implication for prognosis and molecular basis.

The prognostic impact of tumour grading, cytological and architectural patterns and stromal features in diffuse pleural malignant epithelioid mesothelioma (MEM) has been partly studied but not correlated to molecular features. We performed a retrospective study on 92 MEM in our department in order to assess the prognostic role of architectural and stromal patterns, especially tumour to stroma ratio. Secondly, based on The Cancer Genome Atlas (TCGA) database, we analysed the differentially expressed genes in prognostic groups of interest. Our results showed that tumour grading, tumour to stroma ratio and predominant pattern were related to overall survival, p≤0.001, p=0.01 and p=0.001, respectively. In univariate analysis, for high grade tumours hazard ratio (HR) was 4.75 (2.47-9.16), for stroma poor tumours HR=0.016, for predominant tubular or tubulopapillary pattern HR=0.044. In multivariate analysis, high grade tumours were related to overall survival [HR=3.09 (1.50-6.35), p=0.002] and predominant tubular or tubulopapillary pattern [HR=0.56 (0.32-0.99), p=0.045]. In TCGA analysis, after grading of diagnostic slides, we showed that KRTDAP and CXRCR1 expression was higher in low grade tumours, unlike PDZD7 and GPR176 expression which was higher in high grade tumours. FAM81B had a higher expression in stroma poor tumours. We did not find any differentially expressed genes in the architectural patterns group. Our work suggests that tumour grading is an important parameter in MEM with an underlying genomic basis. The role of tumour to stroma ratio needs to be investigated and might also have a genomic basis.

Efficacy and Benefit of Postoperative Chemotherapy in Micropapillray or Solid Predominant Pattern in Stage IB Lung Adenocarcinoma: A Systematic Review and Meta-Analysis.

Background: The benefit of postoperative chemotherapy remains controversial for patients with either a micropapillary or solid pattern in stage IB non-small cell lung cancer. This study is designed to explore the significance of postoperative chemotherapy in patients with either a micropapillary or solid pattern in stage IB lung adenocarcinoma. Method: To conduct the meta-analysis, PubMed, Cochrane Library, Embase and Medline were used to collect literature on long-term follow-up studies published before March, 2021, involving postoperative chemotherapy for patients with both a micropapillary or solid pattern in stage IB lung adenocarcinoma as compared to non-postoperative chemotherapy. Survival data was extracted from the literature, including the overall survival and disease-free survival. Based on overall survival and disease-free survival, hazard ratios and their 95% of confidence intervals were applied to assess the prognostic effect of postoperative chemotherapy. Review Manager software was used to merge the effect size for the meta-analysis. Result: In total, 6 papers with 956 patients were included. In terms of the prognosis of patients suffering from lung cancer when receiving postoperative chemotherapy, this study comprehensively reviews and evaluates the available evidence of micropapillary or solid patterns. After excluding the heterogeneity between the studies, we found that the pooled results from 6 studies report that postoperative chemotherapy was associated with a better overall survival rate when compared with non-postoperative chemotherapy (hazard ratio = 0.58, 95% confidence interval, 0.44-0.77; P = 0.0002). Postoperative chemotherapy also significantly improved the disease-free survival in patients with either a micropapillary or a solid pattern in stage IB lung adenocarcinoma (postoperative chemotherapy vs. non-postoperative chemotherapy, hazard ratio = 0.51, 95% confidence interval, 0.40-0.64; P < 0.001). However, a subgroup analysis showed that compared with non-postoperative chemotherapy, tumor size was unrelated to the prognosis of patients in stage IB undergoing postoperative chemotherapy (hazard ratio = 0.98, 95% confidence interval, 0.94-1.02; P = 0.27). Conclusion: Postoperative chemotherapy results in a better long-term survival rate for patients with either a solid or a micropapillary pattern in stage IB lung adenocarcinoma. Multi-center, prospective, clinical trials are needed to validate our findings.

Desmoplastic small round cell tumor showing solid proliferation with limited desmoplasia and confusing immunohistochemical findings: an autopsy report.

We herein report a variant case of desmoplastic small round cell tumor (DSRCT) showing limited desmoplasia and confusing immunohistochemical findings. A 26-year-old male was referred for multiple abdominal masses. Laparoscopic biopsy showed only the solid proliferation of small round cells, and he was initially diagnosed with small cell carcinoma. At autopsy, the tumor spread diffusely throughout the abdominal and pelvic cavities. Although the tumor was composed of a predominantly solid pattern of small round cells, multiple samples revealed a fibrous stroma in limited areas only. While immunohistochemistry showed the diffuse expression of desmin, CD99, and bcl-2, epithelial differentiation was unclear with few cytokeratin-positive cells and no staining for the epithelial membrane antigen. Although fluorescence in situ hybridization analysis indicated the EWSR1 gene rearrangement, we were unable to exclude Ewing sarcoma considering the morphological and immunohistochemical findings. The diagnosis of DSRCT was confirmed with a reverse transcription-polymerase chain reaction for EWSR1-WT1 fusion transcripts. DSRCT must be included in a differential diagnosis of small round cell tumors even if desmoplasia is not immediately detected, and thorough sampling and a molecular analysis are mandatory.

Micropapillary or solid pattern predicts recurrence free survival benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma.

BACKGROUND: Our study aimed to evaluate the prognostic significance and adjuvant chemotherapy (ACT) benefits of a micropapillary/solid (MS) pattern in patients with stage IB lung adenocarcinoma. METHODS: Patients with pathologically-confirmed stage IB adenocarcinoma who underwent surgical resection between January 2009 and December 2011 were included. The tumors were reclassified into three categories: MS patterns absent (MS-); non-predominant MS patterns (MS+); predominant MS (MS++). The correlations of prognosis and ACT with recurrence-free survival (RFS) were evaluated. RESULTS: Overall, 497 (MS-, n=269; MS+, n=177; MS++, n=51) patients were enrolled in the study. In univariate analysis, the MS+ [hazard ratio (HR), 1.437; 95% confidence interval (CI), 1.030-2.006; P=0.033] and MS++ (HR, 2.818; 95% CI, 1.792-4.432; P<0.001) groups had significantly poor prognosis compared with MS- group. Multivariate analysis revealed that age ≥65 (HR, 1.504; 95% CI, 1.077-2.099; P=0.017), serum level of carcinoembryonic antigen (CEA) ≥10 ng/mL (HR, 1.658; 95% CI, 1.048-2.623; P=0.031) and MS++ (HR, 2.529; 95% CI, 1.550-4.126; P<0.001) were significant prognostic factors. Furthermore, subgroup analysis showed that MS++ patients but not MS- and MS+ derived RFS (recurrence-free survival) benefit from ACT (HR, 0.357; 95% CI, 0.152-0.836; P=0.018). CONCLUSIONS: MS pattern successfully differentiated the prognosis difference among stage IB lung adenocarcinomas and identified patients who benefitted from ACT.

Prognostic factors of adenoid cystic carcinoma of the head and neck in carbon-ion radiotherapy: The impact of histological subtypes.

PURPOSE: The aim of this study was to evaluate the effect of histological subtypes of head and neck adenoid cystic carcinoma (ACC) on the results of carbon-ion radiotherapy (CIRT). MATERIAL AND METHODS: Of the 113 patients with ACC who were treated with CIRT between December 2006 and July 2013, 100 patients with identified histological subtypes were enrolled in this study. CIRT at a total dose of 57.6 or 64.0Gy (RBE) was administered in 16 fractions. Histological grading was defined as the presence or absence of a solid growth pattern. RESULTS: Median follow-up was 60 months. 5-Year local control (LC), overall survival (OS) and distant metastasis free survival (DMFS) of all patients were 68.6%, 74.8% and 65.7%, respectively. On multivariate analysis, the prescribed dose (p=0.001) and gross tumor volume (p=0.002) were significant independent risk factors for LC. No significant difference for local control of solid/non-solid growth patterns was found (p=0.093). Solid growth pattern was an independent risk factor for both OS (p=0.033) and DMFS (p=0.024). CONCLUSIONS: CIRT appears able to locally control solid growth pattern ACC in the head and neck. Improved intervention is needed to extend DMFS and OS.

Solid-Pattern Desmoplastic Small Round Cell Tumor.

Desmoplastic small round cell tumor (DSRCT) is an aggressive small round cell sarcoma that typically occurs intra-abdominally in adolescents and young adults, and is characterized by a recurrent t(11;22)(p13;q12) translocation leading to generation of the EWSR1-WT1 fusion gene, which codes for a chimeric protein with transcriptional regulatory activity. DSRCT has a characteristic histologic appearance of nests of uniform small cells within prominent fibroblastic stroma and immunohistochemically it shows multidirectional differentiation, with expression of epithelial, neural, and muscle markers. We illustrate a case of DSRCT that presented as a large intra-abdominal mass, which harbored EWSR1 rearrangement by fluorescence in situ hybridization and EWSR1-WT1 fusion transcripts by reverse transcription-polymerase chain reaction (RT-PCR), and which histologically had an entirely solid morphology, lacking evidence of desmoplastic stroma. This purely solid variant emphasizes that even when occurring at a typical location, DSRCT may be difficult to recognize when lacking nonclassical morphology. This is of clinical relevance, as DSRCT with this pattern could be misdiagnosed as Ewing sarcoma if RT-PCR is not performed, with resulting prognostic and therapeutic implications.

The Clinical Impact of Solid and Micropapillary Patterns in Resected Lung Adenocarcinoma.

INTRODUCTION: Since the new adenocarcinoma (ADC) classification was presented in 2011, several authors have reported that patients with solid (S) and/or micropapillary (MP) predominant patterns showed a worse prognosis. On the other hand, there are several patients who have S and/or MP patterns even if their patterns are not predominant. However, the evaluation of these patients is uncertain. METHODS: A total of 531 ADCs were examined. We classified the patients into five subgroups according to the proportion of S and/or MP patterns: (1) both patterns absent (S-/MP-), (2) S predominant (S pre), (3) MP predominant (MP pre), (4) S pattern present although not predominant and MP pattern absent (S+ not pre/MP-), and (5) MP pattern present although not predominant (MP+ not pre). RESULTS: Of the 531 ADCs, 384 (72.3%) were classified as S-/MP-, 55 (10.4%) as S pre, 11 (2.1%) as MP pre, 42 (7.9%) as S+ not pre/MP-, and 39 (7.3%) as MP+ not pre. In a univariate analysis, the recurrence-free survival (RFS) and overall survival differed significantly among the five subgroups (p < 0.01 and p < 0.01, respectively). In a multivariate analysis, patients with S-/MP- had significantly higher RFS rates than did those with other subgroups. On the other hand, patients with MP pre had lower RFS rates than did those with other subgroups. CONCLUSION: Patients with S and/or MP patterns have a poorer prognosis even if their patterns are not predominant. The S and/or MP patterns must be treated at the time of diagnosis.

Myoepithelial differentiation in cribriform, tubular and solid pattern of adenoid cystic carcinoma: A potential involvement in histological grading and prognosis.

Adenoid cystic carcinoma (AdCC) is known as a biphasic tumor composed of ductal and myoepithelial cells. The present study aimed to evaluate the amount and distribution of the myoepithelial cells in cribriform, tubular and solid subtypes of AdCC and analyze their relationship with histological grading and prognosis. A panel of myoepithelial markers including CK5/6, p63, p40, D2-40, calponin, α-SMA, S-100, and vimentin, together with a luminal cell marker CK7, and Ki-67 were used for immunohistochemical study in 109 AdCCs that included 38 cribriform, 36 tubular and 35 solid subtypes. The myoepithelial cells were labeled and found lined cystic-like paces, located at the periphery of the cribriform arrangements, and presented at the nonluminal cells of the two-layered tubular structures, while absent or dispersed in the solid pattern. Meantime, the solid subtype presented a higher proliferation rate assessed by mitotic count and Ki-67 labeling index, followed by poorer overall survival and recurrent-free survival. Furthermore, CK7 expression was found higher in solid pattern than in cribriform-tubular subtype, which showed negative correlation with the myoepithelial markers including D2-40, Calponin, α-SMA, p63, p40 and vimentin. The solid pattern of AdCC showed gland differentiation but loss of myoepithelial differentiation with a higher proliferation and more aggressiveness as well as poorer prognosis compared with the cribriform-tubular subtypes, which implies that loss of MEC differentiation might contribute to the poor prognosis of the solid subtype of AdCC. However, further studies are required to clarify its exact role in AdCC progression.