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Surg Oncol. 2021 Feb 15;37:101528. doi: 10.1016/j.suronc.2021.101528. Online ahead of print.
ABSTRACT
BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare malignancy that accounts for less than 1% of primary pancreatic neoplasms. Currently, the lack of large-scale clinical studies limits our understanding of PACC. The aim of this study was to investigate the clinical characteristics and prognosis of PACC.
METHODS: In a retrospective analysis, 52 patients with PACC and 355 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent surgical interventions were evaluated. Clinical characteristics and treatment outcomes were compared between the two groups.
RESULTS: The mean age was lower for patients with PACC than for those with PDAC (mean: 50.8 ± 10.9 versus 59.4 ± 10.9 years; p < 0.001). Except for alpha-fetoprotein (AFP), tumour markers were also lower in the PACC group than the PDAC group. In regard to tumour characteristics, maximum diameters of the primary tumour [median (range): 5.0 cm (1.0-18.2 cm) versus 3.5 cm (0.6-15.0 cm); p < 0.001] and hepatic metastatic lesions [6.7 cm (1.5-12.6 cm) versus 1.2 cm (0.3-3.3 cm); p < 0.001] were larger in patients with PACC than patients with PDAC, but vascular invasion [23.1% (12/52) versus 35.5% (126/355); p = 0.044] and perineural invasion [7.7% (4/52) versus 56.1% (199/355); p < 0.001] were more common in patents with PDAC than in patients with PACC. For treatment, radical resection was performed in 57.7% of patients with PACC, which increased the 5-year survival rate to 31.8%. In regard to prognosis, the 5-year survival rate was 21.4% for PACC and 9.7% for PDAC (p < 0.0001).
CONCLUSIONS: PACC is more indolent than PDAC, which makes early diagnosis more difficult. Although the stage may be advanced at diagnosis, the overall survival (OS) of PACC is much better than that of PDAC, and the prognosis greatly improves after radical resection.
PMID:33611029 | DOI:10.1016/j.suronc.2021.101528
2021 Jan 24. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–.
ABSTRACT
Bronchioloalveolar carcinoma (BAC) is a variant of non-small cell lung cancer (NSCLC) that, in recent years, has received a new identity and nomenclature from the histology perspective. The orphan among lung cancers has found a family, albeit with some newfound stepbrothers and sisters. The overhaul in the classification system of solitary adenocarcinomas has been driven by the purpose of identifying tumors that have an indolent clinical course and can be treated with a more conservative approach and a higher success rate.
Until the previous decade, strict pathologic criteria defined a bronchioloalveolar carcinoma as a tumor arising from terminal bronchiolar and alveolar acinar epithelia with an absence of invasion through the alveolar basement membrane into the pulmonary parenchyma. A growing consensus has been to subclassify adenocarcinoma with radiologic features of ground-glass opacities, with no or minimal extrathoracic spread, and histology demonstrating a lepidic growth pattern in the presence or absence of associated minimally invasive or invasive disease. The subgroup has been renamed adenocarcinoma with lepidic growth and classified into subtypes based on the extent of invasive disease.
PLoS One. 2020 Dec 17;15(12):e0243164. doi: 10.1371/journal.pone.0243164. eCollection 2020.
ABSTRACT
BACKGROUND: Primary acinar cell carcinoma (ACC) is a rare exocrine tumor of the pancreas with unclear clinical characteristics. Our goal was to determine the incidence and update the clinical characteristics and outcomes of ACC.
METHODS: Through the Surveillance, Epidemiology, and End Results (SEER) database, we identified 252 patients with the latest diagnosis of ACC (2004-2016). The age-adjusted incidence (AAI) was calculated using the SEER*Stat Software version 8.3.6. The Kaplan-Meier method was used to draw survival curves and differences among them were compared by the log-rank test. Cox proportional hazards models were used to evaluate factors that had independent predictive effects on the overall survival.
RESULTS: The AAI of pancreatic ACC was on the rise with the mean age at diagnosis of 63.79±14.79 years. Most patients (15.9%) had poorer differentiated tumors. The patients presented with distant stage were 54.4% compared with 53.1% between 1988 and 2003. The 1-, 2-, and 5-years survival rates for pancreatic ACC patients were 53.5%, 34.6%,17.5%, respectively (compared with 78.5%, 67.0%, and 42.8%, between 1988 and 2003). The multivariate COX analysis showed that the patient's age, surgery, chemotherapy, and summary stage, but not marital status were independent prognosis factors for ACC.
CONCLUSIONS: Pancreatic ACC is a highly malignant tumor with an increasing incidence in recent years. The rate of distant metastasis is increasing and the survival rate is worse than in the past, suggesting that it may require more aggressive treatment and follow-up. Surgery, radiotherapy, and chemotherapy are all effective treatments, but prospective studies are still needed to verify them.
PMID:33332471 | PMC:PMC7746196 | DOI:10.1371/journal.pone.0243164
JGH Open. 2020 Jun 29;4(6):1242-1243. doi: 10.1002/jgh3.12380. eCollection 2020 Dec.
ABSTRACT
We present the first case of pancreatic acinar cell carcinoma (PACC) with multiple lesions. A 55-year-old man with a pancretic tail mass on abdominal computed tomography (CT) was admitted to our hospital. Endoscopic ultrasound (EUS) showed a hypoechoic mass, and EUS-guided fine-needle aspiration (EUS-FNA) revealed the mass to be PACC. The patient underwent distal pancreatectomy, and two masses were identified in the pancreatic tail and body. Histologically, both masses had tumor cells similar to acinar cells and were positive for BCL-10. The patient was thus diagnosed with synchronous PACC. Ten months after the surgery, abdominal CT revealed a mass in the remnant pancreas. EUS showed a hypoechoic mass, and EUS-FNA determined it to be PACC. The patient underwent total remnant pancreatectomy. The histological imaging results were similar to those of the first resection. Finally, the patient was diagnosed with synchronous and metachronous PACC. The possibility of multiple occurrences in the pancreas should be considered with PACC.
PMID:33319067 | PMC:PMC7731799 | DOI:10.1002/jgh3.12380
Pancreatology. 2021 Jan;21(1):224-235. doi: 10.1016/j.pan.2020.11.020. Epub 2020 Dec 3.
ABSTRACT
BACKGROUND/OBJECTIVES: Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) of the pancreas and periampullary region are extremely rare and heterogeneous malignancies. Literature is sparse, clinical management is not standardized and little is known about survival outcomes. The aim of this study was to identify pathological and radiological features of MiNEN and assess the outcome of surgical management.
METHODS: Patients undergoing surgery for pancreatic and periampullary MiNEN between 2001 and 2019 were retrospectively analysed based on a prospective database. Histological, radiological and clinical features were assessed. Survival was analysed in a nested case-control study and matched-pair analyses with pure neuroendocrine neoplasms (pNEN) and ductal adeno- or acinar cell carcinomas of the pancreas. A literature review with focus on survival after surgical resection was additionally performed.
RESULTS: Of 13 patients with MiNEN, 5 had acinar-MiNEN and 8 adeno-MiNEN. Two of 5 (40%) acinar-MiNEN and one adeno-MiNEN patients had liver metastases. All but one adeno-MiNEN (88%) showed preoperative radiological features of pancreatic adenocarcinoma, 3 of 5 (60%) acinar-MiNEN exhibited mainly neuroendocrine features. No surgical mortality was observed. The 5-year overall survival rate in all MiNEN was 40%. Five-year survival rate was 58% in adeno-MiNEN and comparable to that of matched ductal adenocarcinomas (36%) and pNEN (48%). Five-year overall survival rate was 20% in acinar-MiNEN, compared to 39% in acinar carcinoma patients and 59% in matched pNEN patients.
CONCLUSIONS: MiNEN are rare and difficult to distinguish from pure adenocarcinoma or neuroendocrine neoplasm preoperatively. Surgical resection would therefore be the treatment of choice in localized tumors.
PMID:33309225 | DOI:10.1016/j.pan.2020.11.020
Oncol Lett. 2021 Jan;21(1):63. doi: 10.3892/ol.2020.12325. Epub 2020 Nov 19.
ABSTRACT
Adenocarcinoma is the most common histological type of lung cancer and has various histologic subtypes, including lepidic, papillary, acinar and invasive mucinous adenocarcinoma. Histologic subtypes are associated with tumor invasiveness. For example, the lepidic subtype is less invasive than the papillary/acinar subtype. Trefoil factor 3 (TFF3) is a small secreting protein that is a member of the trefoil factor family, which is involved in mucosal stabilization and repair through its mitogenic and antiapoptotic activities. TFF3 overexpression is associated with various types of cancer. In lung cancer, TFF3 is expressed significantly in adenocarcinoma. However, the relationship between TFF3 expression and histologic subtypes in lung adenocarcinoma is unclear. The current study immunohistochemically revealed that, beside invasive mucinous carcinoma, the expression of TFF3 in papillary and acinar adenocarcinoma was significantly higher than that in lepidic adenocarcinoma. To further confirm these results, the expression of TFF3 in cases with both lepidic and papillary/acinar areas were examined. The expression of TFF3 in papillary/acinar areas was significantly higher when compared with lepidic areas in a single sample. Furthermore, using the lung adenocarcinoma cell line A549, TFF3-knockdown cells were generated. The results revealed that knockdown of TFF3 attenuated invasion. In vitro and immunohistochemical assays using clinical samples demonstrated that TFF3 expression was associated with lung adenocarcinoma invasiveness. To the best of our knowledge, the current study is the first to report that TFF3 expression was associated with the histologic subtypes of lung adenocarcinoma.
PMID:33281974 | PMC:PMC7709562 | DOI:10.3892/ol.2020.12325
World J Clin Cases. 2020 Nov 6;8(21):5304-5312. doi: 10.12998/wjcc.v8.i21.5304.
ABSTRACT
BACKGROUND: Pancreatic panniculitis is an extremely rare condition associated with different underlying pancreatic disorders and characterized by subcutaneous fat necrosis induced by elevated serum lipase levels. These lesions usually affect the lower extremities and may precede abdominal symptoms of pancreatic disease. Acinar cell carcinoma (ACC) of the pancreas is a rare pancreatic neoplasm, accounting for only 1%-2% of pancreatic tumors in adults.
CASE SUMMARY: We present the case of a 72-year-old man with ACC of the pancreatic head and synchronous liver metastases. Both the primary tumor and liver metastases were resected. Serum lipase was elevated before surgery and decreased to normal postoperatively. Rising serum lipase levels at follow-up led to the diagnosis of hepatic recurrence. This disease progression was then accompanied by pancreatic panniculitis, with subcutaneous fat necrosis and acute arthritis. To the best of our knowledge, only 4 cases have been reported in the literature and each showed a similar association of serum lipase levels with pancreatic panniculitis and progression of ACC.
CONCLUSION: Clinical symptoms and progression of ACC may correlate with serum lipase levels, suggesting potential usefulness as a follow-up biomarker.
PMID:33269263 | PMC:PMC7674712 | DOI:10.12998/wjcc.v8.i21.5304
Cancer Lett. 2021 Feb 28;499:5-13. doi: 10.1016/j.canlet.2020.11.026. Epub 2020 Nov 29.
ABSTRACT
The endocrine FGF21 was discovered as a novel metabolic regulator in 2005 with new functions bifurcating from the canonic heparin-binding FGFs that directly promote cell proliferation and growth independent of a co-receptor. Early studies have demonstrated that FGF21 is a stress sensor in the liver and possibly, several other endocrine and metabolic tissues. Hepatic FGF21 signals via endocrine routes to quench episodes of metabolic derangements, promoting metabolic homeostasis. The convergence of mouse and human studies shows that FGF21 promotes lipid catabolism, including lipolysis, fatty acid oxidation, mitochondrial oxidative activity, and thermogenic energy dissipation, rather than directly regulating insulin and appetite. The white and brown adipose tissues and, to some extent, the hypothalamus, all of which host a transmembrane receptor binary complex of FGFR1 and co-receptor KLB, are considered the essential tissue and molecular targets of hepatic or pharmacological FGF21. On the other hand, a growing body of work has revealed that pancreatic acinar cells form a constitutive high-production site for FGF21, which then acts in an autocrine or paracrine mode. Beyond regulation of macronutrient metabolism and physiological energy expenditure, FGF21 appears to function in forestalling the development of fatty pancreas, steato-pancreatitis, fatty liver, and steato-hepatitis, thereby preventing the development of advanced pathologies such as pancreatic ductal adenocarcinoma or hepatocellular carcinoma. This review is intended to provide updates on these new discoveries that illuminate the protective roles of FGF21-FGFR1-KLB signal pathway in metabolic anomalies-associated severe tissue damage and malignancy, and to inform potential new preventive or therapeutic strategies for obesity-inflicted cancer patients via reducing metabolic risks and inflammation.
PMID:33264641 | PMC:PMC7779663 | DOI:10.1016/j.canlet.2020.11.026
Front Cell Dev Biol. 2020 Nov 17;8:594372. doi: 10.3389/fcell.2020.594372. eCollection 2020.
ABSTRACT
Our previous study found that Notch3 knockout mice exhibit defects in mammary gland development. To elucidate the underlying mechanism, tissue samples were subjected to RNA-seq, GO, and KEGG enrichment analyses and qRT-PCR validation. Of enriched pathways, chemokine signaling pathway and cytokine-cytokine receptor interaction were noticed in both Notch3wt/wt/Notch3wt/- and Notch3wt/wt/Notch3-/- mice, in which the expression of chemokine ligand 2 (CCL2) was sharply reduced in Notch3wt/- and Notch3-/- mammary gland tissues. The Mouse ENCODE transcriptome data reveal that the mammary gland fat pad exhibits a high CCL2, CCR2, and CCR4 expression, indicating that these molecules play important roles during mammary gland development. Specifically, defective mammary glands in Notch3 knockout mice could be partially rescued by CCL2 overexpression lentivirus through intraductal injection. An in vitro study showed that CCL2 overexpression promoted the proliferation, migration, and cancerous acinar formation of 4T1 cells, which could rescue the defective migration of 4T1 cells caused by Notch3 knockdown. We also found that Notch3 transcriptionally regulated the expression of CCL2 in a classical pattern. Our findings illustrated that Notch3-regulating CCL2/CCR4 axis should be an important signaling pathway for mammary gland development and should be a candidate target for breast cancer therapy.
PMID:33244467 | PMC:PMC7685216 | DOI:10.3389/fcell.2020.594372
Pan Afr Med J. 2020 Sep 22;37:80. doi: 10.11604/pamj.2020.37.80.21192. eCollection 2020.
ABSTRACT
Parotid gland tumor is complex and poses diagnostic and therapeutic problems. The purpose of this study was to assess the role of extemporaneous examination in the management of patients with parotid gland tumors. We report a pro and retrospective analytical study of a series of cases of salivary gland tumors, whose data were collected in the ENT and in the department of cervical-facial Surgery at the University Hospital in Casablanca, between January 2012 and December 2015. Seventy two cases of parotid tumors were recorded. The sex-ratio (H/F) was 0.94, 0.76 for patients with benign tumors and 1.62 for patients with malignant tumors. The average age was 47 years (15- 75 years). The median of consultation time was 40 months. Clinical symptoms were dominated by parotid swelling (100%), pain in 25% of patients, facial palsy in 6%, and cervical adenopathies in 10%. Ultrasound was recommended in 80% of patients. MRI was performed in 26% of cases. All patients underwent surgery, 76% of patients underwent exofacial parotidectomies and 24% total conservative parotidectomies. This treatment was associated with ganglion resection in 24% of cases and radiotherapy in 24% of cases. Extemporaneous examination was performed in 71% of patients, its susceptibility was 89% and its specificity 88%. Definitive histological diagnosis was confirmed by anatomopathological examination in all cases. We confirmed benign and malignant tumors in 71% and 29% of cases respectively. Benign tumors were dominated by pleomorphic adenoma (59%), while malignant lesions were dominated by mucoepidermoid carcinoma (38%). The postoperative course was marked by: discrete haematoma in 4% of cases, transient facial palsy in 15%, superinfection of the wound in 3% and post-parotidectomy Frey´s syndrome in 3% of patients. One patient had labial recurrence of acinar cell carcinoma. No cases of death were noted. Parotid gland tumors are characterized by a great histological variability. Differentiation between malignant tumor and benign tumor is often difficult. Currently, MRI is the imaging test of choice. Extemporaneous examinationis is very useful intraoperatively when it is necessary to communicate with the pathologist. Multidisciplinary approach is adopted including ENT, oncological, radiotherapeutic, pathological and radiological approaches. Prognosis depends on the histological type, the stage of progression and treatment.
PMID:33244343 | PMC:PMC7680246 | DOI:10.11604/pamj.2020.37.80.21192
Int J Surg Case Rep. 2020;76:539-544. doi: 10.1016/j.ijscr.2020.10.062. Epub 2020 Oct 19.
ABSTRACT
INTRODUCTION: Pancreatic panniculitis is a rare manifestation of benign and malignant pancreatic disease. The presentation of pancreatic panniculitis is non-specific and thus diagnosis is often delayed. When associated with malignancy, pancreatic panniculitis confers a poor prognosis. This case demonstrates the successful surgical management of this paraneoplastic phenomenon following resection of the underlying pancreatic acinar cell carcinoma and associated liver metastasis.
PRESENTATION OF CASE: A 71-year-old female with debilitating subcutaneous lower limb lesions had a delayed diagnosis of pancreatic panniculitis. A formal diagnosis of pancreatic acinar cell carcinoma with liver metastasis was established and the disease was determined to be resectable. Pre-operatively, serum lipase measured 10,825 U/L. The patient proceeded to an open left hemihepatectomy and radical distal pancreatectomy with complete resection of malignant disease. Six days post-operatively the serum lipase levels normalised, and the panniculitis began to settle. The patient proceeded to adjuvant FOLFORINOX chemotherapy. Twenty months post-surgery, the patient remains disease-free and without any evidence of panniculitis.
DISCUSSION: Due to the rarity of pancreatic acinar cell carcinoma, guidelines based on prospective data do not exist. Most management is based on retrospective analyses. A survival benefit may be achieved with more aggressive surgical management compared to other pancreatic cancer types. Pancreatic acinar cell carcinoma may show a slower rate of disease progression, an increased likelihood of resectability of disease at presentation and is more likely to undergo potentially curative resection.
CONCLUSION: Aggressive surgical management of resectable metastatic pancreatic acinar cell carcinoma can treat pancreatic panniculitis and provide sustained disease-free survival from pancreatic cancer.
PMID:33207427 | PMC:PMC7599369 | DOI:10.1016/j.ijscr.2020.10.062
Front Oncol. 2020 Oct 22;10:580141. doi: 10.3389/fonc.2020.580141. eCollection 2020.
ABSTRACT
Salivary gland carcinomas (SGCs) account for <5% of head and neck malignant neoplasms, further subcategorized in over 20 histological subtypes. For the most part, treatment for advanced disease is guided by morphology. SGCs in general respond poorly to a wide array of standard chemotherapy, with short durability, and significant toxicity. More recently, next-generation sequencing provided significant input on the molecular characterization of each SGC subtype, not only improving diagnostic differentiation between morphologically similar tumor types but also identifying novel driver pathways that determine tumor biology and may be amenable to targeted therapy. Among the most common histological subtype is adenoid cystic carcinoma, which often harbors a chromosome translocation resulting in an MYB-NFIB oncogene, with various degrees of Myb surface expression. In a smaller subset, NOTCH1 mutations occur, conferring a more aggressive pattern and potential sensitivity to Notch inhibitors. Salivary duct carcinomas may overexpress Her-2 and androgen receptors, with promising clinical outcomes after exposure to targeted therapies approved for other indications. Secretory carcinoma, previously known as mammary analog secretory carcinoma, is distinguished by an ETV6-NTRK3 fusion that can both help differentiate it from its morphologically similar acinar cell carcinoma and make it susceptible to Trk inhibitors. In the present article, we discuss the molecular abnormalities, their impact on tumor biology, and therapeutic opportunities for the most common SGC subtypes and review published and ongoing clinical trials and future perspectives for this rare disease.
PMID:33194707 | PMC:PMC7649804 | DOI:10.3389/fonc.2020.580141
Pathologica. 2020 Sep;112(3):210-226. doi: 10.32074/1591-951X-167.
ABSTRACT
Pancreatic malignant exocrine tumors represent the most important cause of cancer-related death for pancreatic neoplasms. The most common tumor type in this category is represented by pancreatic ductal adenocarcinoma (PDAC), an ill defined, stroma-rich, scirrhous neoplasm with glandular differentiation. Here we present the relevant characteristics of the most important PDAC variants, namely adenosquamous carcinoma, colloid carcinoma, undifferentiated carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, signet ring carcinoma, medullary carcinoma and hepatoid carcinoma. The other categories of malignant exocrine tumors, characterized by fleshy, stroma-poor, circumscribed neoplasms, include acinar cell carcinoma (pure and mixed), pancreatoblastoma, and solid pseudopapillary neoplasms. The most important macroscopic, histologic, immunohistochemical and molecular hallmarks of all these tumors, highlighting their key diagnostic/pathological features are presented. Lastly, standardized indications regarding gross sampling and how to compile a formal pathology report for pancreatic malignant exocrine tumors will be provided.
PMID:33179623 | DOI:10.32074/1591-951X-167
Am J Surg Pathol. 2020 Nov 10. doi: 10.1097/PAS.0000000000001618. Online ahead of print.
ABSTRACT
Lung cancer screening has improved mortality among high-risk smokers but has coincidentally detected a fraction of nonprogressive adenocarcinoma historically classified as bronchoalveolar carcinoma (BAC). In the National Lung Screening Trial (NLST) the majority of BAC-comprising 29% of computed tomography-detected stage I lung adenocarcinoma-were considered overdiagnosis after extended follow-up comparison with the control arm. In the current classification, adenocarcinoma in situ and minimally invasive adenocarcinoma have replaced BAC but together comprise only ∼5% of stage I lung adenocarcinoma. Lepidic and subsets of papillary and acinar adenocarcinoma also infrequently recur. We, therefore, propose criteria for low malignant potential (LMP) adenocarcinoma among nonmucinous adenocarcinoma measuring ≤3 cm in total, exhibiting ≥15% lepidic growth, and lacking nonpredominant high-grade patterns (≥10% cribriform, ≥5% micropapillary, ≥5% solid), >1 mitosis per 2 mm, angiolymphatic or visceral pleural invasion, spread through air spaces or necrosis. We tested these criteria in a multi-institutional cohort of 328 invasive stage I (eighth edition) and in situ adenocarcinomas and observed 16% LMP and 7% adenocarcinoma in situ/minimally invasive adenocarcinoma which together (23%) approximated the frequency of overdiagnosed stage I BAC in the NLST. The LMP group had 100% disease-specific survival. The proposed LMP criteria, incorporating multiple histologic parameters, may be a clinically useful "low-grade" prognostic group. Validation of these criteria in additional retrospective cohorts and prospective screen-detected cohorts should be considered.
PMID:33177339 | DOI:10.1097/PAS.0000000000001618
Korean J Radiol. 2020 Oct 30. doi: 10.3348/kjr.2020.0592. Online ahead of print.
ABSTRACT
OBJECTIVE: This study aimed to evaluate the tumor doubling time of invasive lung adenocarcinoma according to the International Association of the Study for Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) histologic classification.
MATERIALS AND METHODS: Among the 2905 patients with surgically resected lung adenocarcinoma, we retrospectively included 172 patients (mean age, 65.6 ± 9.0 years) who had paired thin-section non-contrast chest computed tomography (CT) scans at least 84 days apart with the same CT parameters, along with 10 patients with squamous cell carcinoma (mean age, 70.9 ± 7.4 years) for comparison. Three-dimensional semiautomatic segmentation of nodules was performed to calculate the volume doubling time (VDT), mass doubling time (MDT), and specific growth rate (SGR) of volume and mass. Multivariate linear regression, one-way analysis of variance, and receiver operating characteristic curve analyses were performed.
RESULTS: The median VDT and MDT of lung cancers were as follows: acinar, 603.2 and 639.5 days; lepidic, 1140.6 and 970.1 days; solid/micropapillary, 232.7 and 221.8 days; papillary, 599.0 and 624.3 days; invasive mucinous, 440.7 and 438.2 days; and squamous cell carcinoma, 149.1 and 146.1 days, respectively. The adjusted SGR of volume and mass of the solid-/micropapillary-predominant subtypes were significantly shorter than those of the acinar-, lepidic-, and papillary-predominant subtypes. The histologic subtype was independently associated with tumor doubling time. A VDT of 465.2 days and an MDT of 437.5 days yielded areas under the curve of 0.791 and 0.795, respectively, for distinguishing solid-/micropapillary-predominant subtypes from other subtypes of lung adenocarcinoma.
CONCLUSION: The tumor doubling time of invasive lung adenocarcinoma differed according to the IASCL/ATS/ERS histologic classification.
PMID:33169551 | DOI:10.3348/kjr.2020.0592
Zhonghua Bing Li Xue Za Zhi. 2020 Nov 8;49(11):1142-1146. doi: 10.3760/cma.j.cn112151-20200224-00127.
ABSTRACT
Objective: To investigate the diagnostic role of NR4A3/NOR-1 immunohistochemistry in acinic cell carcinoma (AciCC) of the salivary gland. Methods: A total of 142 tumors were collected from 2004 to 2020 at Nanjing Jinling Hospital, including 24 cases of AciCCs, 12 salivary gland secretory carcinomas,14 salivary duct carcinomas,16 adenoid cystic carcinomas,3 basal cell carcinomas,13 mucoepidermoid carcinomas,7 myoepithelial carcinomas,15 pleomorphic adenomas,15 warthin tumor, 8 myoepithelioma,8 basal cell adenomas, and 7 oncocytomas; 28 normal salivary gland tissues and 2 pancreatic AciCC were also included. Results: NR4A3/NOR-1,a nuclear marker,was positive in 91.7% (22/24) of AciCC of the salivary gland,while DOG1,a membranous and cytoplasmic marker, demonstrated a sensitivity of 95.8% (23/24);there was no significant difference in the overall positive rates(P=0.551), but the stain pattern was different. NR4A3/NOR-1 was negative in normal salivary gland tissues and any other types of tumors in the salivary gland; however,DOG1 showed apical staining in the acinar cells in the salivary gland,as well as salivary gland secretory carcinomas,adenoid cystic carcinomas,basal cell carcinomas,mucoepidermoid carcinomas,myoepithelial carcinomas and basal cell adenomas(P<0.001). NR4A3/NOR-1 showed a high sensitivity(91.7%) and specificity(100%) to identify AciCC of the salivary gland,and in combination with DOG1, the sensitivity increased to 100%. Furthermore, NR4A3/NOR-1 were only positive for AciCC arising from salivary glands but not pancreas(0/2)(P=0.018). Conclusion: NR4A3/NOR-1 is a special and sensitive biomarker for AciCC of salivary glands; combined NR4A3/NOR-1 and DOG1 can be an ideal diagnostic immunohistochemical panel for AciCC.
PMID:33152819 | DOI:10.3760/cma.j.cn112151-20200224-00127
Diagn Cytopathol. 2021 Feb;49(2):287-294. doi: 10.1002/dc.24641. Epub 2020 Oct 31.
ABSTRACT
BACKGROUND: The classification of epithelioid pancreatic neoplasms based on fine-needle aspiration (FNA) is important for proper management, as distinction of pancreatic neuroendocrine neoplasms from other similar appearing lesions can result in significantly different treatment. Mixed acinar-endocrine carcinomas (MAEC) are genetically related to acinar carcinomas and are treated as such. We reviewed cases of MAEC to better characterize their cytologic and immunohistochemical features.
METHODS: Eight FNAs of MAECs were identified and reviewed. A chart review for each case was conducted.
RESULTS: All patients were male, 42-68 years of age, and presented with either Stage 3 or 4 disease. Smear backgrounds of all cases showed naked nuclei without significant necrosis. The smears were cellular with cells arranged in either three-dimensional (3D) clusters with intervening capillaries or singly dispersed. Acinar formation was a prominent feature. Cells were round to oval with small to moderate amounts of delicate cytoplasm. The nuclei were round to oval with mild to moderate anisonucleosis with granular chromatin and small nucleoli. Apoptotic bodies and mitoses were noted in most cases, with Ki67 indices of 10%-48%. All tumors, by definition, demonstrated expression of trypsin and synaptophysin with variable chromogranin expression (50%).
CONCLUSION: The cytology of acinar cell carcinoma shares features with aspirates of other nonductal adenocarcinoma neoplasms of the pancreas. A clue to the diagnosis is that tumors show high Ki67 indices and a diagnosis of MAEC should be excluded anytime a diagnosis of Grade 2 or 3 well-differentiated neuroendocrine tumor or high-grade neuroendocrine carcinoma is in the differential.
PMID:33128511 | DOI:10.1002/dc.24641
Cancer Control. 2020 Jan-Dec;27(1):1073274820969447. doi: 10.1177/1073274820969447.
ABSTRACT
BACKGROUNDS: Acinar cell carcinoma of the pancreas is a rare malignancy, and its features remain unclear. We aimed to analyze the clinical characteristics, treatment and prognosis of acinar cell carcinoma with our institutional case series.
METHODS: Patients diagnosed with acinar cell carcinoma in our hospital between 2005 and 2019 were reviewed. Investigations on clinicopathological features, treatment details and long-term survival were performed.
RESULTS: A total of 45 pathologically confirmed acinar cell carcinomas were identified. The median age at diagnosis was 58 years with a male-to-female ratio of 3.1:1. There were 24 (53.3%) localized, 5 (11.1%) locally advanced and 16 (35.6%) metastatic cases, with a pancreatic head-to-body/tail ratio of 1:1.4 for all the primary lesions. In the localized group, there were 10 pancreatoduodenectomy, 12 distal pancreatectomy, 1 total pancreatectomy, and 1 distal pancreatectomy combined with proximal gastrectomy. Among the locally advanced and metastatic cases, 13 patients received chemotherapy, 1 received concurrent radiochemotherapy, 1 underwent synchronous resection of primary tumor and liver metastasis, 1 underwent palliative operation, 1 underwent exploratory laparotomy, and 4 required no treatment. The median overall survival of this series was 18.9 months with a 5-year survival rate of 19.6%. Moreover, the resected acinar cell carcinoma patients were associated with prolonged survival compared with the unresected cases (36.6 vs. 8.5 months, P < 0.001).
CONCLUSIONS: Surgical resection could improve the long-term survival of acinar cell carcinoma patients, which might also improve the prognosis of selected metastatic cases. Large-scale studies are needed to further clarify the biological behavior and clinical features, and to seek the optimal treatments.
PMID:33121259 | DOI:10.1177/1073274820969447
Diagn Cytopathol. 2020 Oct 28. doi: 10.1002/dc.24648. Online ahead of print.
ABSTRACT
Cerebrospinal fluid (CSF) evaluation for total and differential cell count is a common practice in pathology for evaluation of various disease conditions. Although rare, these CSF samples yield interesting and unusual morphological findings, which are not only of academic interest, but also may play key roles in diagnosis. For diagnosing metastatic carcinoma in brain and meninges, CSF examination is one of the important tools along with imaging studies. Metaplastic breast carcinoma (MBC) encompasses a rare (<1% of all breast cancers), aggressive and highly heterogeneous group of tumors. MBC is almost always estrogen receptor, progesterone receptor and Her2 negative (triple negative) and shows frequent early distant metastases as well as sub-optimal response to systemic therapies. The involvement of leptomeninges is most commonly associated with these triple- negative subtypes. In this report, we present an unusual case of malignant cells with prominent intracytoplasmic granules in CSF smears of a 46-year-old female with metastatic MBC with acinar differentiation. An extensive review of literature in English language did not return any other reports of a similar finding.
PMID:33118313 | DOI:10.1002/dc.24648
J Dermatol. 2021 Feb;48(2):237-241. doi: 10.1111/1346-8138.15646. Epub 2020 Oct 18.
ABSTRACT
Pancreatic panniculitis (PP) is a rare clinical variant of subcutaneous fat necrosis, developing in patients with a variety of pancreatic diseases such as acute or chronic pancreatitis, tumors and cysts. The tumor-associated PP represents a noteworthy skin manifestation of underlying internal malignancies, also known as dermadrome. Among causative pancreatic tumors, acinar cell carcinoma is the most frequent malignancy; however, little is known about how the origin of tumor cells and progression stage of pancreatic tumors potentially contribute to the establishment of panniculitis. Here, we present a 69-year-old Japanese male case of clinically aggressive PP on the bilateral legs, whose skin lesions developed prior to the diagnosis of occult pancreatic tumor and liver metastasis. Moreover, the immunopathology of the pancreatic lesion revealed neuroendocrine tumor (NET), a rare pathological variant. Skin lesions immediately spread to the upper limbs with extensive ulcerations and necrosis, accompanied by high levels of serum lipase and elastase, but not with other pancreatic enzymes. He died 2 months after the initial development of the skin lesion due to rapid deterioration of general condition. We reviewed 14 cases, including ours, of PP with NET in the pancreas thus far reported, to identify the clinicopathological characteristics regarding to what extent this rare complication could reflect the clinical course of pancreatic tumors and overall prognosis. Our published work review found that the disease has a significant male predominance (male : female, 13:1) and cases with occult pancreatic tumors died within 4 months after the development of their skin lesions. Our case was the poorest prognostic outcome. This report emphasizes that dermatologists should recognize PP with NET, reflecting a fatal prognosis, and to make a prompt diagnosis.
PMID:33073392 | DOI:10.1111/1346-8138.15646
Clin Imaging. 2021 Jan;69:332-338. doi: 10.1016/j.clinimag.2020.07.011. Epub 2020 Jul 25.
ABSTRACT
INTRODUCTION: This study assessed (i) the ability to identify the solid components of part-solid nodules (PSN) during computed tomography (CT) guided lung biopsy (CTGLB), (ii) the ability of CTGLB to assess the invasive nature of a nodule on pathology.
MATERIALS AND METHODS: Sixty-nine nodules were studied in 68 patients who underwent CTGLB between 1/1/2014 and 10/31/2015. Diagnostic CT images and CTGLB images were reviewed. On diagnostic CT images, nodules were classified as ground glass nodules (GGN) or PSNs. Nodule size, location, and percentage of solid component were recorded. At the time of biopsy, the ability to visualize the solid component of a PSN, depth of lesion from skin, and ability to identify the needle within the solid component were recorded.
RESULTS: There were 42 (61%) part-solid nodules and 27 (39%) GGNs. During biopsy, it was possible to differentiate the solid from the ground glass components in 35 (83%) PSNs. Fifty-nine (86%) nodules were neoplastic based on biopsy pathology (all non-small cell lung carcinoma). Thirty-nine (66%) were resected. In all cases biopsy pathology and surgical pathology agreed regarding the presence of lung carcinoma. In 6 (15%) cases biopsy pathology demonstrated purely lepidic growth but had some non-lepidic growth on surgical pathology, including 2 cases with acinar growth as a dominant pattern.
CONCLUSION: In most patients, the solid and ground glass components of a PSN were distinguishable when performing a CTGLB. In a minority of patients, discrepancy was noted between biopsy pathology and surgical pathology regarding the invasive nature of a nodule.
PMID:33059184 | DOI:10.1016/j.clinimag.2020.07.011
Theranostics. 2020 Aug 29;10(24):10861-10873. doi: 10.7150/thno.45440. eCollection 2020.
ABSTRACT
Rationale: A high tumor-to-healthy-tissue uptake ratio of radiolabeled ligands is an essential prerequisite for safe and effective peptide receptor radionuclide therapy (PRRT). In the present study, we searched for novel opportunities to increase tumor-specific uptake of the radiolabeled minigastrin analogue [177Lu]Lu-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2 ([177Lu]Lu-PP-F11N), that targets the cholecystokinin B receptor (CCKBR) in human cancers. Methods: A kinase inhibitor library screen followed by proliferation and internalization assays were employed to identify compounds which can increase uptake of [177Lu]Lu-PP-F11N in CCKBR-transfected human epidermoid carcinoma A431 cells and natural CCKBR-expressing rat pancreatic acinar AR42J cells. Western blot (WB) analysis verified the inhibition of the signaling pathways and the CCKBR level, whereas the cell-based assay analyzed arrestin recruitment. Biodistribution and SPECT imaging of the A431/CCKBR xenograft mouse model as well as histological analysis of the dissected tumors were used for in vivo validation. Results: Our screen identified the inhibitors of mammalian target of rapamycin complex 1 (mTORC1), which increased cell uptake of [177Lu]Lu-PP-F11N. Pharmacological mTORC1 inhibition by RAD001 and metformin increased internalization of [177Lu]Lu-PP-F11N in A431/CCKBR and in AR42J cells. Analysis of protein lysates from RAD001-treated cells revealed increased levels of CCKBR (2.2-fold) and inhibition of S6 phosphorylation. PP-F11N induced recruitment of β-arrestin1/2 and ERK1/2 phosphorylation. In A431/CCKBR-tumor bearing nude mice, 3 or 5 days of RAD001 pretreatment significantly enhanced tumor-specific uptake of [177Lu]Lu-PP-F11N (ratio [RAD001/Control] of 1.56 or 1.79, respectively), whereas metformin treatment did not show a significant difference. Quantification of SPECT/CT images confirmed higher uptake of [177Lu]Lu-PP-F11N in RAD001-treated tumors with ratios [RAD001/Control] of average and maximum concentration reaching 3.11 and 3.17, respectively. HE staining and IHC of RAD001-treated tumors showed a significant increase in necrosis (1.4% control vs.10.6% of necrotic area) and the reduction of proliferative (80% control vs. 61% of Ki67 positive cells) and mitotically active cells (1.08% control vs. 0.75% of mitotic figures). No significant difference in the tumor vascularization was observed after five-day RAD001 or metformin treatment. Conclusions: Our data demonstrates, that increased CCKBR protein level by RAD001 pretreatment has the potential to improve tumor uptake of [177Lu]Lu-PP-F11N and provides proof-of-concept for the development of molecular strategies aimed at enhancing the level of the targeted receptor, to increase the efficacy of PRRT and nuclear imaging.
PMID:33042258 | PMC:PMC7532663 | DOI:10.7150/thno.45440
BMJ Case Rep. 2020 Oct 10;13(10):e236509. doi: 10.1136/bcr-2020-236509.
ABSTRACT
The sclerosing variant of mucoepidermoid salivary gland carcinoma is extremely rare. It is nearly impossible to diagnose this condition preoperatively. We present a case of a 23-year-old woman with a 1-year history of left parotid enlargement with inconclusive fine-needle aspiration cytology results. MRI showed an irregular parotid mass, and subsequent partial parotidectomy confirmed the diagnosis. We discuss the diagnostic pitfalls of this condition and provide a review of the literature surrounding its pathogenesis and management.
PMID:33040037 | PMC:PMC7549475 | DOI:10.1136/bcr-2020-236509
Zhonghua Bing Li Xue Za Zhi. 2020 Oct 8;49(10):1036-1040. doi: 10.3760/cma.j.cn112151-20191215-00800.
ABSTRACT
Objective: To investigate the expression status and diagnostic value of SRY related high mobility group box 11 (SOX-11) and transcription factor E-3 (TFE3) in solid pseudopapillary tumors of pancreas (SPTPs). Methods: Thirty-eight cases of SPTPs, 36 cases of well-differentiated pancreatic neuroendocrine tumors (PanNETs) and six cases of pancreatic acinar cell carcinomas (PACCs) were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from 2012 to 2019. The expression of SOX-11, TFE3 and β-catenin was detected by immunohistochemistry, and the TFE3 gene status was detected by FISH in 18 cases of SPTPs. Results: Among the 38 SPTP patients, 29 were female and 9 were male, with a mean age of 50 years; among 36 PanNET patients, 32 were female and 4 were male, with a mean age of 39 years; for the six PACC patients, four were male and two were female, with a mean age of 60 years. β-catenin was positive in all 38 SPTPs, but was negative in all 36 PanNETs and 5/6 PACCs. SOX-11 was positive in 35/38 (92.1%) of SPTPs, but was negative in all 36 PanNETs and 6 PACCs. TFE3 was positive in 36/38 (94.7%) of SPTPs, but was negative in all 36 PanNETs and 6 PACCs. Among these three tumors, the specificity and sensitivity of β-catenin were 97.6% and 100.0%, the specificity and sensitivity of SOX-11 were 92.1% and 100.0%, the specificity and sensitivity of TFE3 were 94.7% and 100.0%, respectively. There was a significant difference of the expression status of all three markers in SPTPs compared with PanNETs and PACCs (P<0.01). The results of SOX-11 and TFE3 immunostaining showed high consistency (Kappa>0.6). No gene rearrangement (0/18) of TFE3 was found in SPTPs. Conclusion: SOX-11 and TFE3 are highly expressed in SPTPs, and their specificity in the differential diagnosis of SPTPs is better than that of β-catenin.
PMID:32992419 | DOI:10.3760/cma.j.cn112151-20191215-00800
Monogr Clin Cytol. 2020;26:92-108. doi: 10.1159/000455737. Epub 2020 Sep 28.
ABSTRACT
Non-ductal tumors of the pancreas are relatively rare tumors and include pancreatic neuroendocrine tumors (PanNETs), poorly differentiated neuroendocrine carcinomas, acinar cell carcinoma, solid pseudopapillary neoplasm, and pancreatoblastoma. These tumors have a morphology and biology that is distinct from that of ductal neoplasms of the pancreas. PanNETs are the most common tumors among this group. A brief summary of each tumor is described here with an emphasis on the clinical presentation, cytological features, tumor histology, and immunohistochemical profile. Differential diagnoses for each entity are also discussed.
PMID:32987393 | DOI:10.1159/000455737