Solid Growth Pattern Research Articles

Molecular Alterations in Relation to Histopathological Characteristics in a Large Series of Pediatric Papillary Thyroid Carcinoma from a Single Institution.

Simple SummaryPapillary thyroid carcinoma (PTC) in pediatric patients shows different characteristics compared with PTC in adults. In this large mono-institutional cohort of pediatric PTCs, tumor tissue samples have been analyzed for point mutations and fusions. Overall, molecular alterations were detected in 131 out of 163 PTCs (80%). Fusion-driven PTCs showed more aggressive clinico-pathological features compared to mutation-driven and wild-type cases. These results highlight the importance of testing pediatric PTCs for gene rearrangement in routine characterization of tumors.Papillary thyroid carcinoma (PTC) presents distinct clinico-pathological and molecular differences in children compared with adult patients. Whether the presence of rearrangements or point mutations is associated with aggressive PTC clinical presentation is still controversial. In this study, PTCs diagnosed in patients aged less than 18 years were retrospectively searched from the institutional archive and tumor tissue was tested for point mutations in BRAF and RAS genes and for rearrangements in RET, NTRK1, NTRK3, ALK, PPARG, BRAF and THADA. A total of 163 PTCs were analyzed. Point mutations were found in 83 (51%) and gene fusions in 48 cases (30%). The most frequent alteration was the BRAFV600E mutation (36.8%), followed by NTRK3 fusion (11%), NRAS mutation (10.4%) and RET fusion (10.4%). Fusion-driven PTCs showed more frequently infiltrative growth, larger tumors, extrathyroidal extension and N1b disease. PTCs showing solid growth pattern were significantly enriched in gene fusions. This is one of the largest cohorts of pediatric PTCs. Fusion-driven tumors most frequently show aggressive pathological features; the search for rearrangements, especially in tumors with solid areas, could improve the characterization of pediatric PTCs and offer possible therapeutic options.

NONSEMINOMATOUS GERM CELL TUMOR METASTATIC TO THE MAXILLA

<h3>Background</h3> Extragonodal germ cell tumors (GCTs) primarily affect the sacrococcygeal region. Head and neck GCT is rare and accounts for 3% of pediatric neoplasms. Only isolated cases of metastatic GCT have been reported. <h3>Objective</h3> To report a unique case of a metastatic nonseminomatous GCT of mixed phenotype with yolk sac tumor, embryonal carcinoma, and immature teratoma components. <h3>Clinical Findings</h3> A 13-year-old male patient presented with a rapidly enlarging, painless right maxillary tuberosity mass, present for 4 months. The tumor was on the buccal gingiva extending to the hard and soft palate posteriorly. Ipsilateral submandibular lymphadenopathy was evident. No pathology was noted on the panelipse and periapical radiographs. The clinical impression was that of a lymphoma or Kaposi sarcoma. <h3>Pathologic Findings</h3> The histology showed an extensively infiltrative high-grade malignancy composed of small, round, blue discohesive tumor cells demonstrating a solid growth pattern, with areas of adenocarcinoma and squamous differentiation with keratinization. Surface dysplasia was not present. Brisk mitotic activity was noted. Immunohistochemistry revealed positivity with for AE1/AE3, SALL4, Glyplican 3, and OCT3/4, confirming the diagnosis of a metastatic nonseminomatous GCT of mixed phenotype. <h3>Summary</h3> Benign teratomas are the most common childhood extragonodal tumors, followed by yolk sac tumors, which frequently arise in the ovaries and testis. Yolk sac tumors that frequently arise in the ovaries and testis have been reported but continue to be a rare extragonodal tumor and are difficult to diagnose. This report reviews germ cell tumors in the spectrum of metastatic disease to the oral cavity.

Modulating hepatocarcinogenesis by porto-systemic vein shunting in a high-fat diet mouse model

Abstract Objective Non-alcoholic fatty liver disease (NAFLD) is an increasingly common disease, which can lead to hepatocellular carcinoma (HCC). It is associated with an increased portal pressure, which can alter the intestinal barrier, increase the translocation of bacterial products, and further worsen NAFLD. We hypothesized that this vicious circle can be broken by surgical porto-systemic vein shunting (PSVS), and previously demonstrated that PSVS can decrease the histological features of NAFLD in a high-fat diet (HFD) mouse model. We now test whether PSVS can also impact de-novo hepatocarcinogenesis. Methods C57BL/6 mice received HFD starting from 4 weeks of age. HCC was induced by intraperitoneal injection of DEN at 25mg/kg on week 2 and PSVS (n = 18) (or sham surgery (n = 18)) are created at 8 weeks. HCC burden was assessed by MRI and, finally, by macroscopic and histomorphology assessments. HCC features of aggressiveness, including solid growth pattern and fat component have been also evaluated. Results At 40 weeks of HFD feeding, tumors were identified in all the animals. Shunted HFD mice showed a reduced number of tumor nodules compared to sham (median nodules 8 vs 14, -42.9%; p = 0.0471) while associated to a greater average total tumor volume (709.3 vs 197 mm3, +258,6%; p = 0.0245). This correlated with an increased median tumor volume in shunted mice (16.30 vs 72.45 mm3, +344,5%; p = 0.0011). Notably, HCC histology of shunted mice was hallmarked by accentuated trend concerning HCC fatty change combined to a less pronounced solid growth pattern (p = 0.193). Conclusion PSVS leads to the presence of larger HCCs, potentially linked to the proportionally increased arterial supply of the liver. However, it demonstrates a protective effect on HCC carcinogenesis (&amp;lt; number of tumors). Collectively, this data suggests that portal pressure could represent a potential therapeutic target to attenuate liver steatosis and NAFLD-related HCC carcinogenesis.

Solid variant of papillary thyroid carcinoma: An analysis of 28 cases with current literature

IntroductionSolid variant papillary thyroid cancer (SVPTC) is a rare variant of papillary thyroid carcinoma (PTC) and its prognostic value is still unclear. Therefore, we re-evaluate the histopathological and clinicopathological features of 28 patients with SVPTC in the light of current literature. Material-methodsOf the 1308 cases were previously diagnosed with PTC and 28 (2,1%) of them which had been diagnosed with SVPTC were re-evaluated retrospectively. ResultsOf the 28 patients with SVPTC, 85.7% were female, mean age was 45.18 years and mean tumor diameter was 2.96 cm. Microscopically; tumors had a solid growth pattern amounting to at least 50.0% of the tumor volume. In all cases the tumor cells had characteristic nuclear features of conventional PTC. 11 patients had multifocal tumors, extrathyroidal extension was present in 4 patients and vascular invasion was observed in 7 cases. Regional lymph node metastases were noted in 2 (7.1%) cases at the time of diagnosis. One patient died because of locally advanced disease. Another patient is alive with lung metastases after 48 months from the initial surgery. There was no evidence of local recurrence in other patient. ConclusionsSVPTC is a rare variant of PTC that should be considered in the differential diagnosis of tumors which show a solid/trabecular growth pattern in the thyroid. It has poor prognostic features such as widespread angioinvasion, extrathyroidal extention, lymph node metastasis, and distant organ metastasis. Multicenter studies involving large number of cases are needed to reveal the prognostic significance of SVPTC, with standardized diagnostic criteria.

Challenging of frozen diagnoses of small sclerosing pneumocytoma

AimsAn increasing number of small pulmonary nodules are being screened by CT, and an intraoperative diagnosis is necessary for preventing excessive treatment. However, there is limited literature on the frozen...

Clinicopathological features of hybrid oncocytic/chromophobe renal cell tumor

Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of hybrid oncocytic/chromophobe tumor (HOCT) of the kidney and its associations with renal oncocytoma (RO) and eosinophilic chromophobe renal cell carcinoma (eChRCC). Methods: A total of 8 HOCT cases were collected from 2008 to 2019 at the Affiliated Hospital of Qingdao University (5 cases) and 971 Hospital of PLA Navy (3 cases), Qingdao, China for morphological studies, immunohistochemical staining and follow-up. The immunohistochemical results of HOCT were compared with those of 27 typical RO and 17 eChRCC. Results: Among the 8 patients, 3 were male and 5 were female. Their ages ranged from 39 to 75 years (median: 56 years). All cases were sporadic. Seven patients were asymptomatic and one suffered from lumbago. During a mean follow-up of 37 months in 7 patients, none of them developed tumor recurrence or metastasis. Seven cases were solitary and one was multiple. The tumor size ranged from 1.4 to 5.7 cm (mean, 3.6 cm). The cut surface of the tumors was dark red or yellowish. Histologically, the tumors were well-defined. Six cases were directly adjacent to the surrounding renal tissue, 2 cases had pseudocapsule, 3 cases showed entrapped renal tubules at the edge of tumor tissue, and one circumscribed with focal infiltrating borders. There were two types of histological morphology: one type (4 cases) was composed of mixed areas of otherwise typical RO and areas resembling chromophobe renal cell carcinoma; another type (4 cases) showed the morphological characteristics of both RO and eChRCC. Three second-type tumors showed nest-like, trabecular, and solid growth patterns with conspicuous edematous stroma. The cell border was conspicuous and the cytoplasm showed an eosinophilic appearance. The nuclei were small and round with clear perinuclear halo. One tumor showed a multi-nodular and solid growth pattern, and the cytoplasm was eosinophilic, hypochromatic or transparent. The nuclei were small and round, and some of them had obvious perinuclear halo. Immunohistochemically, the tumor cells in all 8 cases were positive for Ksp-cad but negative for vimentin. CD117 was diffusely positive in 6/8 cases. CK7 staining showed patchy positivity in 6/8 cases. S-100A1, cyclin D1 and claudin7 showed variable positivity in 4/8, 6/8 and 5/8 cases, respectively, but the range and intensity were narrower and weaker than those in RO and eChRCC. Conclusions: HOCT is a low-grade eosinophilic renal tumor with morphological characteristics resembling RO and eChRCC. The combined application of immunohistochemical stains of CK7, CD117, Ksp-cad, cyclin D1, claudin7 and S-100A1 may play an auxiliary role in the differentiation of the three tumors. HOCT has a good prognosis after surgical resection and can be regarded as a tumor with uncertain malignant potential.

SWI/SNF-deficient thoraco-pulmonary neoplasms.

The SWI/SNF complexes are major regulators of gene expression and their alterations occur in a large array of cancers both of epithelial and mesenchymal lineages. Malignant rhabdoid tumors were the first malignancies linked to deregulation of these complexes with the involvement of SMARCB1 in their development but genetic alterations affect all subunits in other malignancies. In the chest and lung regions, SMARCA4 (BRG1) is the most frequently altered subunit and is involved in the pathogenesis of two subtypes of tumors, including bona fide carcinomas (SMARCA4-deficient non-small cell lung cancers) but also undifferentiated tumors that harbor an undifferentiated phenotype close to those of malignant rhabdoid tumors (SMARCA4-undifferentiated tumors). Although their histogenesis is yet to be fully understood, these tumors are associated with distinct clinical and pathological features even though some overlapping features have been reported in rare cases. SMARCA4 deficiency is easily asserted by immunohistochemistry that show the loss of nuclear expression of the protein in the nuclei of tumor cells. These tumors are commonly associated with high-grade cytological features, rhabdoid cytomorphology, solid architecture and extensive necrosis. The typical immunohistochemical signature of SMARCA4-UT combines co-inactivation of SMARCA2 (BRM) and the overexpression of SOX2 and SALL4. No specific therapeutic strategies have been so far developed for SMARCA4-deficient neoplasms. SMARCB1 subunit is involved in the development of several SMARCB1-deficient sarcomas on top of malignant rhabdoid tumors that may develop in the thorax. Malignant rhabdoid tumors affect mostly children of less than 5y. The differential diagnosis includes epithelioid sarcomas, malignant myoepithelial tumors or myoepithelial carcinomas, extra-skeletal myxoid chondrosarcomas and synovial sarcomas.

Histomorphological and immunophenotypical spectrum of cutaneous myoepitheliomas: A series of 35 cases.

Myoepithelial tumors comprise a group of mesenchymal lesions that show heterogeneous histomorphological features, including dual epithelial, neural, and myoid differentiation. Cutaneous myoepithelioma is a rare neoplasm that is composed primarily of myoepithelial cells and represents one end of a histopathological spectrum of cutaneous myoepithelial neoplasms including chondroid syringoma and myoepithelial carcinoma. These tumors display a wide histopathological spectrum and immunophenotypical profile often showing epithelial and myoepithelial differentiation. In this series, we studied 35 cases of cutaneous myoepitheliomas. Our cases highlighted the broad histopathological range where most cases showed a non-infiltrative and non-encapsulated tumor exclusively located in the dermis and with no subcutaneous involvement. The majority of our cases had a solid growth pattern (syncytial pattern) and the remainder of cases had a multinodular growth pattern. The tumor cells were epithelioid in 23 cases, spindled in eight cases and there was a mixture of epithelioid and spindled cells in four cases. Mitotic figures ranged from 0 to 5 per 10 HPF. By immunohistochemistry epithelial membrane antigen (EMA) was expressed in 59% of cases S100 was positive in 88% of cases, CAM 5.2 was positive in 16% of cases, AE1/AE3 was positive in 44% of cases, p63 was positive in 17% of cases, smooth muscle actin was positive in 38% of cases, desmin was positive in 6% of cases, calponin was positive in 22% of cases, and glial fibrillary acidic protein was positive in 36% of cases. In addition, there were five cases without EMA, keratin, or p63 expression that only showed S100 expression. We describe a large series of cutaneous myoepitheliomas delineating their histomorphological spectrum and immunophenotypical profile. Awareness of some of the unusual histopathological features and the heterogeneous immunohistochemical may pose difficulties for the diagnosis.

Cytokeratin expression in plasmablastic lymphoma - a possible diagnostic pitfall in the routine work-up of tumours.

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoma that frequently arises at extranodal sites in the setting of immunosuppression. The diagnosis of PBL is complex, owing to a frequent solid or cohesive growth pattern, and an often unusual immunophenotype. Several case reports have described cytokeratin (CK) expression in PBL, introducing a diagnostic pitfall. The aim of this study was to determine the frequency of CK expression in PBL in the largest series available to date. By using immunohistochemistry in a cohort of 72 PBLs, we identified CK8/18 positivity in 11 of 72 cases (15%) and AE1/3 positivity in six of 65 cases (9%), clearly contrasting with a control series of non-PBL aggressive B-cell lymphomas (one of 96 diffuse large B-cell lymphomas), as well as with data in the literature describing only occasional CK expression in haematological neoplasms. Our data indicate CK expression in a substantial number (15%) of PBLs. In view of the particular morphological features of PBL and its frequent negativity for the common leukocyte antigen and B-cell markers, this feature represents a pitfall in the routine diagnostic work-up of PBL, and requires more extensive immunohistochemical and molecular characterisation of cases entering the differential diagnosis.

Clinicopathological features and differential diagnosis of eosionphilic chromophobe renal cell carcinoma

Objective: To investigate the clinicopathological characteristics of eosionphilic Chromophobe renal cell carcinoma (eChRCC), and differences in morphology, immunophenotype and clinical prognosis betweeneChRCC, renal oncocytoma(RO) and classic Chromophobe renal cell carcinoma (cChRCC). Methods: The clinicopathologic data of 17 patients diagnosed as eChRCC from the Affiliated Hospital of Qingdao University (13 cases) and 971 Hospital of PLA Navy (4 cases) from October 2006 to February 2019 were collected. Immunohistochemical analysis was carried out to compare the immunophenotypes between 17 cases with ChRCC, 27 cases with RO and 30 cases with cChRCC. Resuls: Among the 17 patients, seven were males and ten were females, and the age ranged from 40 to 75 years (median 54 years). Clinically, 15 cases of 17 were found accidentally by physical examination. The tumor size ranged from 1.8 cm to 10.0 cm (average 5.7 cm) and the cut surface of 15 cases were solid, one case was solicl and cystic, and one was cystic. Most showed gray to red, and partially soft, gray to yellow appearances. Microscopically, most tumors presented solid growth pattern with vary number of alveolar structures (12 cases). Some were predominately characterized by cystic structure (3 cases), alveolar structure(1 case) and microcapsule structure (1 case). There were boundaries with varying degrees of clarity between tumor cells in 16 cases. The cytoplasm of tumor cells was eosinophilic and the nuclei were small round or irregular with focal perinuclear haloes in 14 cases. Large polygonal cells with light-stained cytoplasm appeared focally in 9 cases, and edematous areas with scarce tumor cells were found in 4 cases. Among 7 cases, 4 cases focally invaded peripheral renal parenchyma, 2 cases invaded adipose tissues outside the renal capsule, and 1 case presented invasion of renal sinus. Immunohistochemically, all cases were moderate to strong positive for EMA and claudin-7. CK7, CD117 and Ksp-cad were highly expressed with the expression rates of 12/17, 15/17, 14/17, respectively. Cyclin D1, AMACR, CD10, S100A1, and RCC were rarely expressed with the expression rates of 4/17, 3/17, 4/17, 1/17 and 1/17, respectively. On the contrary, all cases were negative for vimentin, CAⅨ, HMB45 and Melan A. The Ki-67 proliferation index of the 17 cases was 1%‒5%. Follow-up data were available for all 17 patients from 7 to 154 months. Among them, 15 patients were alive without tumor recurrence or metastasis, one patient died of pulmonary metastasis after 31 months of surgery and one patient died of hepatic metastasis after 38 months of surgery. Conclusion: eChRCC has overlapping morphology and immunophenotype with RO. eChRCC is characterized by solid nest or alveolar structure, distinct border between tumor cells, perinuclear halos and lacking of interstitial looseness and edema. Scattered large polygonal cells with light-stained cytoplasm in tumor tissue play a significant role in the diagnosis of eChRCC. The positive expression of CK7, CD117, claudin-7 and Ksp-cad, and negative expression of cyclin D1, S100A1 are helpful to the diagnosis and differential diagnosis of eChRCC. The prognosis of eChRCC after complete surgical resection is excellent and few cases may have long-term metastasis. There is no significant difference in prognosis between eChRCC and cChRCC, but eChRCC shows better outcome than RO.

Aberrant Diffuse Intense CD10 Expression In P16 Positive Undifferentiated Endometrial Carcinoma: A Diagnostic Dilemma

Abstract Introduction/Objective High-grade endometrial neoplasms frequently pose a diagnostic challenge on purely histologic evaluation due to their ambiguous morphologic features. High grade endometrioid adenocarcinoma, serous carcinoma, undifferentiated carcinoma, and a minority of sarcoma cases can present with a solid growth pattern. Methods We present a 59-year-old patient who underwent a hysterectomy and bilateral salpingo-oophorectomy for a biopsy proven FIGO grade 2 endometrial carcinoma. Results Grossly, the entire endometrial cavity was involved by a hemorrhagic tumor. Microscopic examination showed the entire specimen to be replaced by predominantly non-cohesive diffuse sheets of mitotically active, pleomorphic cells without any glandular, papillary, serous or clear cell features.The differential diagnosis included undifferentiated carcinoma, serous carcinoma, carcinosarcoma, stromal sarcoma and other tumors including high- grade lymphoma. By immunohistochemistry, the tumor cells showed variable positivity for CK7, EMA, CK19, CK18, CK8, AE1/AE3, pan-keratin, CAM5.2, CD56, synaptophysin, p53, cyclinD1 and with a high Ki-67 proliferation index of 80%. The tumor was diffusely/intensely positive for CD10 and P16 while being negative for ER, PR, PAX8, HPV, mesenchymal and lymphoid markers. While diffuse/intense CD10 positivity and ER/PR negativity raised a concern for stromal sarcoma component, the above phenotype confirmed an aggressive/high grade carcinoma. Diffuse/intense p53 and p16 expression raised a consideration of serous carcinoma, but morphology and absence of PAX-8 failed to support this diagnosis. Undifferentiated carcinoma of the endometrium is a high-grade carcinoma which has been recognized as a distinct entity with diffuse p16 and p53 positivity in the absence of PAX-8 and hormone receptors. Positive vimentin, along with a negative HPV, confirmed the endometrial rather than cervical origin of this neoplasm. Conclusion By reporting this case, we draw attention to the previously unreported diffuse intense CD10 expression in undifferentiated carcinoma of endometrium to avoid misdiagnosis with considerations that include stromal sarcoma.

Gastric Adenocarcinoma with Enteroblastic Differentiation: A Rare Find

Abstract Casestudy: Gastric adenocarcinoma with enteroblastic differentiation (GAED), also called clear cell gastric carcinoma, is a subtype of alpha-fetoprotein (AFP) producing adenocarcinoma. GAED is not a well-documented malignancy. Due to rarity, it is often skipped from the list of gastric adenocarcinoma subtypes. We report a case of Gastric adenocarcinoma with enteroblastic differentiation in a 69-year-old male, who had an endoscopy that revealed an ulcerated, circumferential, malignant-appearing mass at the distal esophagus. The patient then underwent proximal gastrectomy with distal esophagectomy. Received was a portion of the proximal stomach and distal esophagus. On gross examination, a 2.6 cm ulcerated mass was present at the gastroesophageal junction with white, friable, and focally necrotic cut surface. H&amp;E stained slides demonstrated a malignant tumor composed of cuboidal to columnar neoplastic cells with clear cytoplasm and prominent nucleoli. The neoplastic cells were arranged in tubular, solid, and trabecular growth patterns. There were also areas of admixed conventional moderately differentiated adenocarcinoma with overlying glandular dysplasia and focal intestinal metaplasia. Immunohistochemical stains demonstrated tumor positivity for CDX2 (strong) and AFP (focal). Neuroendocrine markers were negative within the tumor. In Conclusion, GAED is a rare malignancy with distinctive clinicopathologic features and associated aggressive behavior. Morphology and immunohistochemical stains are helpful in making the diagnosis of this rare malignancy.

Laparoscopic resection of a neuroendocrine tumor that almost fully replaced tailgut cysts: a case report

BackgroundNeuroendocrine tumors (NETs) originate from neuroendocrine cells, which are found throughout the body. NETs occur principally in the gastrointestinal tract (approximately 65%) and bronchopulmonary tract (approximately 25%) but rarely occur in the presacral space. Aside from primary and metastatic lesions, there have been reports of NETs occurring in the presacral space arising from tailgut cysts, teratomas, and imperforate anus. We herein report a rare case of laparoscopic resection of a NET in the presacral space, which almost fully replaced tailgut cysts.Case presentationA 68-year-old woman was referred to our hospital for surgery of a right inguinal hernia, but preoperative computed tomography revealed an asymptomatic 43-mm mass in the presacral space. Magnetic resonance imaging showed a multilocular solid mass with clear boundaries and a slightly high signal intensity on T1- and T2-weighted images. Positron emission tomography showed 18F-fluorodeoxyglucose uptake. Thus, we suspected a malignant tumor and performed laparoscopic resection to obtain a definitive diagnosis. Macroscopically, the tumor was 43 mm in size with clear boundaries, and the cut surface was a gray-white solid component. Histopathological findings revealed that the tumor was composed of relatively uniform cells with fine chromatin, with round to oval nuclei arranged in solid, trabecular, or rosette-like growth patterns. Small cysts lined with stratified squamous epithelium and columnar epithelium were observed along with solid components of the tumor, which is a feature of tailgut cysts. Therefore, the final diagnosis was NET Grade 1 arising from tailgut cysts. No recurrence was observed within 1 year after surgery.ConclusionsWe performed en bloc laparoscopic resection of a NET arising from tailgut cysts in the presacral space without injury. In cases of a solid lesion in the presacral space, not only the primary disease but also the pathological condition with tissue transformation and replacement should be considered, as in this case.

Low-grade oncocytic tumour of kidney (CD117-negative, cytokeratin 7-positive)

BackgroundThe term low-grade oncocytic tumour of kidney is an emerging entity describing CD117-negative and cytokeratin 7-positive indolent tumors with overlapping morphological features between oncocytic tumors.Case presentationWe present herein the case of a 77-year-old female with a 3.2-cm nodule in mid pole of the left kidney. The tumor was uniformly oncocytic with solid, compact nested and trabecular growth patterns. There was common areas of transition to central zones of stromal edema with marked tumor hypocellularity and growth in cords. Some of these areas had adjacent fresh hemorrhage. Immunohistochemistry showed strong and diffuse expression of cytokeratin 7 and negativity for cKIT/CD117.ConclusionThe proper use of this new diagnostic category avoids labeling such tumors as unclassified renal cell carcinoma – a broad category with different morphologic features and heterogenous prognosis.

Compact portable multiphoton microscopy reveals histopathological hallmarks of unprocessed lung tumor tissue in real time.

During lung cancer operations a rapid and reliable assessment of tumor tissue can reduce operation time and potentially improve patient outcomes. We show that third harmonic generation (THG), second harmonic generation (SHG) and two‐photon excited autofluorescence (2PEF) microscopy reveals relevant, histopathological information within seconds in fresh unprocessed human lung samples. We used a compact, portable microscope and recorded images within 1 to 3 seconds using a power of 5 mW. The generated THG/SHG/2PEF images of tumorous and nontumorous tissues are compared with the corresponding standard histology images, to identify alveolar structures and histopathological hallmarks. Cellular structures (tumor cells, macrophages and lymphocytes) (THG), collagen (SHG) and elastin (2PEF) are differentiated and allowed for rapid identification of carcinoid with solid growth pattern, minimally enlarged monomorphic cell nuclei with salt‐and‐pepper chromatin pattern, and adenocarcinoma with lipidic and micropapillary growth patterns. THG/SHG/2PEF imaging is thus a promising tool for clinical intraoperative assessment of lung tumor tissue.

Colorectal Adenocarcinomas Harboring ALK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 12 Cases and Review of the Literature.

This study determined the frequency and the clinicopathologic and genetic features of colorectal carcinomas driven by oncogenic fusions of the anaplastic lymphoma kinase gene (ALK). Of the 8150 screened tumors, 12 (0.15%) were immunohistochemically ALK-positive with D5F3 antibody. These cancers harbored CAD-ALK (n=1), DIAPH2-ALK (n=2), EML4-ALK (n=2), LOC101929227-ALK (n=1), SLMAP-ALK (n=1), SPTBN1-ALK (n=4), and STRN-ALK (n=1) fusions, as detected by an RNA-based next-generation sequencing assay. ALK fusion carcinomas were diagnosed mostly in older patients with a 9:3 female predominance (median age: 72 y). All tumors, except a rectal one, occurred in the right colon. Most tumors were stage T3 (n=7) or T4 (n=3). Local lymph node and distant metastases were seen at presentation in 9 and 2 patients. These tumors showed moderate (n=6) or poor (n=3) glandular differentiation, solid medullary growth pattern (n=2), and pure mucinous morphology (n=1). DNA mismatch repair-deficient phenotype was identified in 10 cases. Tumor-infiltrating lymphocytes were prominent in 9 carcinomas. In 4 carcinomas, tumor cells showed strong, focal (n=3), or diffuse programmed death-ligand 1 immunoreactivity. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 tumors. Four patients died of disease within 3 years, and 7 were alive with follow-up ranging from 1 to 8 years. No mutations in BRAF, RAS, and in genes encoding components of PI3K-AKT/MTOR pathway were identified. However, 1 tumor had a loss-of-function PTEN mutation. Aberration of p53 signaling, TP53 mutations, and/or nuclear accumulation of p53 protein was seen in 9 cases. ALK fusion colorectal carcinomas are a distinct and rare subtype of colorectal cancers displaying some features of mismatch repair-deficient tumors.

Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival

Diffuse malignant mesothelioma (DMM) of the pleura is a rare and aggressive disease, wherein the long-term survival (LTS) rate is low. The epithelioid subtype is the most prevalent form of DMM with the best prognosis. To study prognostic histopathologic factors associated with extended survival in epithelioid DMM, we examined 43 tumors from patients with survival more than five years (LTSs) and compared the findings with 84 tumors from a reference group (RG) with average survival. We analyzed the tumors considering previously published histopathological prognostic features and attempted to identify additional morphological features predictive of extended survival. Most of the LTS tumors presented with nuclear grade I (n=34, 90%) and a tubulopapillary growth pattern (n=30, 70%). One LTS tumor had necrosis. In contrast, nuclear grade II (n=49, 61%) and solid growth pattern (n=59, 70%) were more frequent in the RG, and necrosis was present in 16 (19%) tumors. We also evaluated the association of asbestos lung tissue fiber burden quantified from autopsy samples with histopathological features and found that elevated asbestos fiber was associated with higher nuclear grade (P<0.001) and the presence of necrosis (P=0.021). In univariate survival analysis, we identified the following three novel morphological features associated with survival: exophytic polypoid growth pattern, tumor density, and single mesothelium layered tubular structures. After adjustments, low nuclear grade (P<0.001) and presence of exophytic polypoid growth (P=0.024) were associated with prolonged survival. These results may aid in estimating DMM prognosis.

Cervical lymph node metastasis in adenoid cystic carcinoma of the salivary glands: A clinicopathologic study

To investigate the incidence and clinicopathologic features of cervical lymph node metastasis in salivary gland adenoid cystic carcinoma (AdCC). Retrospective analysis was made in 798 AdCC patients who underwent tumor resection during January, 2001 to January, 2019 in Peking University School and Hospital of Stomatology, especially the clincopathologic characteristics of 82 cases with lymph node metastasis. In the study, 82 of the 798 patients were identified with cervical lymph node metastasis, which was confirmed by histopathological examination. The palate, the region of sublingual gland and mouth floor, and the parotid were the frequently involved primary sites for AdCCs. The general incidence rate of lymph node metastasis was approximately 10%. The submandibular gland, the region of sublingual gland and mouth floor, and the mobile tongue were the most frequent sites of lymph node metastasis with the incidence rates of 20.8%, 16.1%, and 15.1%, respectively; while lymph node metastasis was uncommon in the tumors which were the origin from the palate and parotid, with incidence rates of 6.1% and 3.4%, respectively. Most AdCC cases (70.7%) showed the classic "tunnel-style" metastatic pattern of occurrence, and the level I and II regions were the most frequently involved areas. The 5-year and 10-year overall survival rates of the patients with lymph node metastasis were 77.4% and 20.6% respectively, while the 5-year and 10-year overall survival rates of the patients with no lymph node metastasis were 83.5% and 57.6%, respectively. The univariate analysis demonstrated that statistically significant differences in the overall survival for the presence of lymph node metastasis (P<0.001). In the meantime, the 5-year disease-free survival rate of the patients with lymph node metastasis also showed statistically significant differences to that of the AdCC patients with no lymph node metastasis. In addition, the primary site and histological grade were significantly associated with lymph node metastasis, and the high-grade solid growth pattern was identified as a strong predictor for the occurrence of lymph node metastasis. Cervical lymph node metastasis has a high tendency of occurrence in submandibular gland and tongue-mouth floor complex, and the high-grade solid growth pattern could be taken as a strong predictor for the occurrence of lymph node metastasis, which correlates to poor prognosis of AdCC patients. A selective neck dissection should be considered as a management in such patients.

2020 challenges in diagnosis and staging of lung cancer

Pathology plays an important role in diagnosis and management of patients with non-small cell lung carcinoma (NSCLC). The current (2015) WHO classification of lung tumours includes histologic and immunophenotypic (IHC) criteria. Adenocarcinomas are the primary focus of shifting nomenclature, emphasising histologic patterns with clinical and biological relevance. Minimally invasive and lepidic-predominant non-mucinous adenocarcinomas represent well-differentiated tumours, while solid and/or micropapillary growth patterns signify poorly-differentiated adenocarcinomas. Poorly-differentiated carcinomas that cannot be classified on the basis of histology alone can instead be subclassified using a limited IHC panel targeting TTF-1 and p63/p40. For adenocarcinomas with non-invasive (lepidic) components, pT staging hinges on the size and extent of only the invasive component. Multifocal tumours are staged based on a combination of gross growth characteristics and histologic findings. Pathology’s role extends beyond diagnosis and staging in response to expectations that cells and tissues will be available for expanded biomarker testing in patients with advanced stage disease. Testing strategies for predictive biomarkers frequently include a combination of immunohistochemistry and increasingly comprehensive molecular profiling as single gene assays become less common. Panels are constructed to balance the number of actionable targets over and against our ability to test extremely small amounts of viable tumour.

Poorly differentiated thyroid carcinoma of childhood and adolescence: a distinct entity characterized by DICER1 mutations.

Poorly differentiated thyroid carcinomas (PDTC) in young individuals are rare and their clinical and histopathologic features, genetic mechanisms, and outcomes remain largely unknown. Here, we report a detailed characterization of a series of 6 PDTC in patients ≤ 21 years old defined by Turin diagnostic criteria studied for mutations and gene fusions characteristic of thyroid cancer using targeted next-generation sequencing (NGS) and whole exome sequencing (WES). All tumors had solid, insular or trabecular growth pattern and high mitotic rate, and 5 out of 6 tumors showed tumor necrosis. Targeted NGS assay identified somatic mutations in the DICER1 gene in 5 of 6 (83%) tumors, all of which were “hotspot” mutations encoding the metal-ion binding sites of the RNase IIIb domain of DICER1. WES was performed in 5 cases which confirmed all hotspot mutations and detected 2 tumors with additional inactivating DICER1 alterations. Of these two, one was a germline pathogenic DICER1 variant and the other had loss of heterozygosity for DICER1. No other mutations or gene fusions characteristic of adult well-differentiated thyroid cancer and PDTC (BRAF, RAS, TERT, RET/PTC and other) were detected. On follow-up, available for 5 patients, 3 patients died of disease 8-24 months after diagnosis, whereas 2 were alive with no disease. The results of our study demonstrate that childhood- and adolescent-onset PDTC are genetically distinct from adult-onset PDTC in that they are strongly associated with DICER1 mutations and may herald DICER1 syndrome in a minority. As such, all young persons with PDTC may benefit from genetic counselling. Furthermore, their clinically aggressive behavior contrasts sharply with the indolent nature of the great majority of thyroid tumors with DICER1 mutations reported to date.