Squamous Cell Carcinoma Component Research Articles

Clinicopathological characteristics and immune microenvironment of breast squamous cell carcinoma

Objective: To investigate the clinicopathological characteristics of breast squamous cell carcinoma and to analyze the relationship between its immune microenvironment tumor infiltrating lymphocytes (TILs) and prognosis. Methods: Forty-four cases of primary squamous cell carcinoma of the breast diagnosed and treated in the First Affiliated Hospital of Air Force Medical University, Xi'an, China from January 2006 to July 2022 were selected. Their clinicopathological characteristics were analyzed. The cell composition of TILs was evaluated using immunohistochemistry (Mainly markers of B lymphocytes, T lymphocytes and plasma cells). The relationship between TILs and prognosis was also analyzed. Results: The 44 patients of breast squamous cell carcinoma were all female and all were invasive carcinoma. Eight cases (8/44, 18.2%) were squamous cell carcinoma, while 36 cases (36/44, 81.8%) were mixed squamous cell carcinoma. The mixed components included non-specific carcinoma and spindle cell metaplastic carcinoma (17 cases each). One case contained ductal carcinoma in situ of the breast and 1 case contained tubular carcinoma. The proportion of squamous cell carcinoma was 10% to 90%. The cases with pure squamous cell carcinoma often had a large cystic cavity, which was lined by atypical squamous epithelium, while infiltrating squamous cell carcinoma nests were seen in the breast tissue around the cystic cavity. Immunohistochemical staining showed that p63 and CK5/6 were expressed in the squamous cell carcinoma component, but ER, PR and HER2 were not, except for one case of HER2 1+. The positive rates of TRPS1 and PDL-1 were 76% and less than 1%, respectively. Fifteen cases were in the high TILs group (TILs≥30%) and 29 cases were in the low TILs group (TILs<30%). Twenty-three patients were followed up for 5 to 118 months. Among them, 12 died within 3 years and 9 were alive at the end of the follow up. There was no significant difference in TNM stage, TILs and prognosis between simple squamous cell carcinoma and mixed squamous cell carcinoma. Conclusions: Breast squamous cell carcinoma can be divided into simple squamous cell carcinoma and mixed squamous cell carcinoma. There are differences in gross findings and histology between the simple and mixed squamous cell carcinoma of the breast. Sufficient samples should be taken to avoid missing the diagnosis of a minor squamous component. The prognosis of patients with high TILs is significantly better than that of patients with low TILs. The expression rate of TRPS1 in primary squamous cell carcinoma of breast is high and helpful to the differential diagnosis from metastatic squamous cell carcinoma.

Clinicopathological and molecular characteristics of esophageal carcinoma with ductal differentiation: analysis of 17 cases

Objective: To investigate the clinicopathological features and molecular genetic characteristics of esophageal carcinoma with ductal differentiation, and to summarize the experiences in its diagnosis and treatment. Methods: A total of 17 cases of esophageal carcinoma with ductal differentiation diagnosed in Ningbo Clinical Pathological Diagnosis Center, Ningbo, China from June 2011 to December 2022 were collected. The clinical information and pathological diagnosis was reviewed. The tumor histological features and immunohistochemical results were analyzed. The next-generation sequencing was performed to detect and analyze the gene mutations in tumor samples. Results: The 17 patients included in this study were 54-77 years old, with a median age of 66 years. There were 16 males and 1 female. Among them, 9 cases were mainly carcinoma with ductal differentiation. The squamous epithelium on the tumor's surface was accompanied by high-grade intraepithelial neoplasia. The tumor and atypical squamous epithelium were transitional, and the focus was accompanied by various proportions of squamous cell carcinoma component (less than 10%). The other 8 cases were mostly squamous cell carcinoma, basaloid squamous cell carcinoma or sarcomatoid carcinoma with various degrees of tumor specific differentiation and focal area of carcinoma with ductal differentiation (less than 10%). The tumor cells in the area with ductal differentiation were mainly arranged in small tubes, while the tubes showed a double-layer structure, including the inner cells and outer cells of the lumen. Immunohistochemical results showed that the outer cells of the tumorous tubules expressed p63, p40, CK5/6 and CK34βE12, while the inner cells expressed CK7. Compared with esophageal squamous cell carcinoma reported in the literature, the frequency of gene mutations such as MYC (P=0.002), TP63 (P=0.002), CDKN1C (P=0.002) and NFE2L2 (P=0.045) was significantly lower in this group of cases. At the signaling pathway level, the mutation frequency of NOTCH signaling pathway (P=0.041) was significantly higher, while the mutation frequencies of NRF2 pathway (P=0.013) and PI3K pathway (P=0.009) were significantly lower than that of esophageal squamous cell carcinoma. Conclusion: Esophageal carcinoma with ductal differentiation is a type of esophageal carcinoma with unique morphology, and its molecular changes are also significantly different from those of conventional esophageal squamous cell carcinoma.

Submucosal gland differentiation and implications in esophageal basaloid squamous cell carcinomas.

Esophageal basaloid squamous cell carcinoma (BSCC) is a heterogenous entity with multilineage differentiation. It lacks systematical analysis on submucosal gland differentiation (SGD) due to the histological diversity and low incidence of esophageal BSCC. This study aims to find the correlation of SGD and clinicopathological features. A total of 152 esophageal BSCCs were separated into three histological groups: pure, mixed, and borderline group. The clinicopathological features were compared between different groups. The prevalence of SGD was also compared between cases of different groups. A panel of antibodies were used to identify SGD. The pure group differed from the mixed and borderline groups in many aspects, lymph node metastasis (LNM), cancer embolus, perineural invasion, and advanced stage occurred less frequently in the pure group (P<0.01). The pure group had a better but statistically insignificant overall survival (P=0.097). The squamous cell carcinoma (SCC) component or focal squamous differentiation was present in metastatic lymph nodes in almost all mixed BSCCs (95.7%, 22/23) with LNM. The LNM rate of superficial (T1b) BSCCs (17.6%, 6/34) was comparable to that of superficial (T1b) SCCs (18.5%, 57/308). However, LNM exclusively occurred in superficial mixed (3/5) and borderline (3/10) BSCCs. The IHC results demonstrated a prevalence of SGD in pure group (77%, 43/56). SGD is considered to be a favorable factor, while the squamous differentiation or invasive SCC component is an adverse factor in esophageal BSCCs. Refinement of classification is a promising way to improve patient management.

Granulation tissue-like spindle cell (sarcomatoid) carcinoma of the head and neck: a deceptively bland-looking underdiagnosed malignancy

The diagnosis of head and neck spindle cell squamous carcinoma (SC-SCC) is often challenging. Lesions with a prominent inflammatory infiltrate and reactive vessels may have a granulation tissue-like appearance, therefore being difficult to distinguish from reactive lesions, like contact ulcers, post-intubation granulomas, inflammatory pseudotumors, or benign vascular lesions. In this study, we analyzed the clinicopathological features of a series of 17 head and neck SC-SCC with granulation tissue-like appearance. All patients, but two, were males, ranging in age between 57 and 80 years. The larynx was the most frequently affected site (n = 12), followed by the tongue (n = 4). One tumor was hypopharyngeal. Most consult cases were submitted with benign suggestion or because of unexpected recurrences of granulation tissue polyps. Histologically, all lesions consisted of an ulcerated polypoid proliferation of moderately to markedly atypical spindle cells, with a minor component of conventional invasive or in situ squamous carcinoma. At least one cytokeratin cocktail was positive in 13 cases. The staining was limited to a few neoplastic cells in most cases. Positivity for p63, p40, and cytokeratins 5/6 was detected only in the conventional squamous cell carcinoma component, when present. ALK1 was negative in all cases. Sixteen cases were tested for p53 and all showed aberrant expression (12 diffusely positive and 4 of null-phenotype). The diagnosis of granulation tissue-like SC-SCC is challenging due to the close clinical and histological overlap with several benign conditions. Since the expression of epithelial markers is limited, the use of an immunohistochemical panel including p53 is recommended.

Primary Oral Mixed Neuroendocrine-Non-neuroendocrine Neoplasm (MiNEN): A Rare Case Report and Review of the Literature.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare tumors recently characterized by the presence of both neuroendocrine and non-neuroendocrine components within the same tumor tissue. Although MiNEN found their place in the WHO classification for various organs, this composite tumor in the head and neck region remains exceptionally rare. We present a case of primary oral MiNEN in a 64-year-old male located on the left side of lower gingiva. Biopsy raised suspicion of neuroendocrine carcinoma (NEC) and the patient underwent partial mandibulectomy. The resected specimen showed two distinct components of NEC and squamous cell carcinoma (SCC) with the confirmation of immunohistochemical markers. There has been no sign of recurrence nor metastasis 6years after the surgery. In addition, we have conducted a review of published cases with potential relevance to this entity, resulting in five cases. The diverse terminology reinforces the need for a standardized classification system of oral/head and neck MiNENs.

Liver metastasis composed of pure squamous cell carcinoma component from pancreatic pure ductal adenocarcinoma: a case report

BackgroundLiver metastasis of pure squamous cell carcinoma (SCC) from pancreatic ductal adenocarcinoma has not been previously reported.Case presentationA 66-year-old man underwent a computed tomography scan 3 years after surgery for pancreatic head cancer, and the scan revealed a mass lesion in the right lobe of the liver. A liver tumor biopsy was performed, and SCC was diagnosed. Whole sections of the pancreatic head cancer were re-evaluated, but no areas of SCC-like differentiation were identified. Although the pathology differed between the pancreas and liver, metastasis of adenosquamous carcinoma was considered. Three courses of gemcitabine plus nab-paclitaxel were administered to treat the liver metastasis of pancreatic cancer, but no response was attained. Therefore, primary SCC of the liver was considered and hepatic resection was performed. The tumor had invaded the diaphragm, and S5/6 partial hepatic resection with right diaphragm resection was performed. Pathological examination showed pure SCC of the liver, which differed from the pancreatic cancer. KRAS mutations were evaluated in the pancreatic and liver tumor specimens, and Q61R mutation was identified in both specimens. This pure SCC of the liver was diagnosed as metastasis from pancreatic cancer not by histology but by genetic analysis.ConclusionsThis is the first reported case of pure SCC liver metastasis from pancreatic cancer without a squamous cell component in the primary tumor. Evaluation of KRAS mutations in both specimens was useful for diagnosis.

Clinicopathologic study of stage I adenosquamous carcinoma of the lung.

Adenosquamous carcinoma of the lung is a characteristic tumor that has both adenocarcinoma and squamous cell carcinoma components. Adenosquamous carcinoma is reported to have an aggressive clinical course, but its clinicopathological features and prognosis are unclear in the early stage. Patients who underwent surgical resection for pathological stage I non-small cell lung cancer between April 2009 and December 2014 were retrospectively reviewed. Preoperative and postoperative data, histologic characteristics and outcomes of patients with adenosquamous carcinoma (n=40) were compared to adenocarcinoma (n=598) and squamous cell carcinoma (n=131) patients. Factors affecting prognosis, particularly on recurrence, were assessed via Cox regression analyses. Patients with adenosquamous carcinoma had a worse prognosis than did patients with adenocarcinoma and squamous cell carcinoma in terms of 5year overall (66.7%) and recurrence-free survival rates (44.9%), as well as a significantly higher recurrence rate (13/40 patients, 32.5%). Multivariable Cox regression analysis for recurrence-free survival rates revealed that the histology of adenosquamous carcinoma was an independent factor for recurrence (hazard ratio: 2.473, 95% confidence interval: 1.328-3.367; P=0.0004). High serum carcinoembryonic antigen levels (hazard ratio: 5.962) and vascular invasion (hazard ratio: 4.899) were identified as risk factors for recurrence, and patients with adenosquamous carcinoma tended to have distant relapses, such as in the brain. Early-stage adenosquamous carcinoma of the lung is a histological type associated with severe prognosis and postoperative recurrence, often in distant sites, in approximately one-third of cases. High serum carcinoembryonic antigen levels and vascular invasion might be risk factors of recurrence.

Genetic analysis of low-grade adenosquamous carcinoma of the breast progressing to high-grade metaplastic carcinoma

PurposeLow-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few LGASC cases with high-grade transformation have been reported; however, the genetics underlying malignant progression of LGASC remain unclear.MethodsWe performed whole-genome sequencing analysis on five MBCs from four patients, including one case with matching primary LGASC and a lymph node metastatic tumor consisting of high-grade MBC with a predominant metaplastic squamous cell carcinoma component (MSC) that progressed from LGASC and three cases of independent de novo MSC.ResultsUnlike de novo MSC, LGASC and its associated MSC showed no TP53 mutation and tended to contain fewer structural variants than de novo MSC. Both LGASC and its associated MSC harbored the common GNAS c.C2530T:p.Arg844Cys mutation, which was more frequently detected in the cancer cell fraction of MSC. MSC associated with LGASC showed additional pathogenic deletions of multiple tumor-suppressor genes, such as KMT2D and BTG1. Copy number analysis revealed potential 18q loss of heterozygosity in both LGASC and associated MSC. The frequency of SMAD4::DCC fusion due to deletions increased with progression to MSC; however, chimeric proteins were not detected. SMAD4 protein expression was already decreased at the LGASC stage due to unknown mechanisms.ConclusionNot only LGASC but also its associated high-grade MBC may be genetically different from de novo high-grade MBC. Progression from LGASC to high-grade MBC may involve the concentration of driver mutations caused by clonal selection and inactivation of tumor-suppressor genes.

Perianal Cutaneous Spindle Cell Squamous Cell Carcinoma With Myxoid Stroma: Case Report and Literature Review.

Spindle cell squamous cell carcinoma with myxoid stroma is a rare variant of squamous cell carcinoma with sarcomatoid morphology. We report a case of a 75-year-old woman with an ulcerated polypoid cutaneous mass in the perianal area. The patient had a history of clear cell renal cell carcinoma. Microscopy revealed an invasive myxoid spindle cell carcinoma without the classic squamous cell carcinoma component. The immunohistochemical study demonstrated diffuse positive reactions for p63, AE1/3, and CK5/6. The tumor cells were negative for desmin, smooth muscle actin, S100, and CD34. Fluorescent in situ hybridization was negative for EWSR1 gene rearrangement. Follow-up was remarkable for recurrence of tumor in 2 months after complete resection with negative surgical margin. This is the first case report of perianal spindle cell squamous cell carcinoma with myxoid stroma with a literature review of previous case reports from different locations.

ADENOSQUAMOUS LUNG CARCINOMA COMPLICATED WITH MARANTIC ENDOCARDITIS AND CHRONIC DISSEMINATED INTRAVASCULAR COAGULATION

Background: Adenosquamous lung carcinoma is a relatively rare subtype of non-small-cell lung cancer that contains both adenocarcinoma (ADC) and squamous cell carcinoma (SCC) components. It is difficult to reach a proper diagnosis before surgery, with the histopathological examination of the resected specimen being the method of choice. A supplementary immunohistochemistry examination of the sample is needed. In order to initiate targeted treatment, molecular testing is mandatory. Case presentation: A 47-year-old female, smoker (15 packs-year), without pathological personal history, presented for fatigue and moderate bilateral leg edema for about 3 months. The blood tests showed severe microcytic, hypochromic anemia and chronic disseminated intravascular coagulation. Computed tomography (CT) scan revealed a tumor in the right basal pleura with secondary pleural effusion, multiple lymphadenopathies, disseminated in the mediastinum, abdominal and pelvic cavity. Two other tumors were noticed, one in the right breast (7 mm) and the other in the vesicouterine pouch (7/10 mm). Prior to lung biopsy, a transthoracic and then transesophageal echocardiography were performed, highlighting the presence of a band on the aortic valve, suggesting marantic endocarditis. Tumor markers were also elevated. In evolution, the patient became bradypsychic, with head CT showing a brain metastasis in the left high-parietal region. Immunohistochemistry examination of the biopsy sample suggested a adenosquamous lung carcinoma. Conclusion: We reported the diagnostic path of a rare subtype of lung cancer in a young female without known comorbidities, with an atypical presentation - multiple extrapulmonary non-metastatic manifestations: metabolic etiology - weight loss, fatigue; vascular and hematological etiology – marantic endocarditis (a very rare complication), severe microcytic, hypochromic anemia and chronic disseminated intravascular coagulation; neurological etiology – peripheral sensorimotor neuropathy of the right arm. A tissue biopsy was performed from the most accessible region – 1/3 inferior right thorax, posterior axillary line. The particularity of the adenosquamous lung carcinoma in this case lies in multiple metastases in less common sites (breast, vesicouterine pouch and probably kidney).

Immunohistological study of ovarian mature cystic teratoma with extremely elevated SCC antigen level

Squamous cell carcinoma (SCC) antigen is a reliable tumor marker for various cancers, including cervical cancer and lung cancer, and was recently reported to correlate with the severity of inflammatory skin diseases such as atopic dermatitis. Herein, we present a case of a 47-year-old female patient who presented with acute abdomen rupture due to a mature cystic teratoma of the ovary, approximately 11 cm in diameter on imaging examination, prompting emergency laparoscopic surgery. The patient had no symptoms of atopic dermatitis. The operative findings showed no evidence of torsion, but the membrane was partially ruptured, leading to the leakage of the cyst contents. The operation was completed after excising the adnexa and intraperitoneal lavage. The postoperative results revealed a markedly high serum SCC antigen level of 55.3 ng/dL, which was normalized at 2 months postoperatively. Postoperative histopathological examination revealed no squamous cell carcinoma component but a marked lymphocytic infiltrate under the squamous epithelium, suggesting a high degree of inflammation. Additionally, immunostaining demonstrated a cluster of differentiation (CD) 8+ lymphocyte predominance over CD4+ lymphocytes, similar to the histology of atopic dermatitis. Altogether, our findings suggest that the abnormally high SCC antigen levels might be attributed to the presence of severe inflammation in the mature cystic teratoma rather than an underlying malignancy and support the notion that SCC antigen may be a useful marker beyond its established role in cervical and lung cancers.

Vulvar Adenoid Cystic Carcinoma with Squamous Cell Carcinoma Component.

Adenoid cystic carcinoma (ACC) is a major histological type of salivary gland cancer but an uncommon form of vulvar cancer. Salivary gland ACC occasionally dedifferentiates into high-grade carcinoma, resulting in poor prognoses. The dedifferentiated component is usually a poorly differentiated cribriform or solid carcinoma, whereas squamous cell carcinoma (SCC) is exceptional. Herein, we report the case of a 78-year-old woman with vulvar ACC, including an SCC component. She presented with a vulvar nodule that had been present for 30 years and increased in size over the past few years. Magnetic resonance imaging showed a ball-like mass with high intensity on T1-weighted images and high intensity with non-uniformity on T2-weighted images. Considering the systemic and social conditions, the tumor was maximally resected without lymphadenectomy. Histologically, the tumor was composed of a marginal ACC component with a central SCC component. Stage IB vulvar cancer, which was assumed to originate from the Bartholin's gland, was diagnosed. She has survived over 2 years without additional treatments after the surgery. In this case, we assumed that slowly progressive indolent ACC could be dedifferentiated to high- grade SCC. According to our review of available literature, dedifferentiation of vulvar ACC with a high-grade SCC component has not been specifically documented. Although the nature of dedifferentiated vulvar cancer is unclear, it should be noted that high-grade dedifferentiation can occur in long-lasting vulvar masses.

PRIMARY ADENOSQUAMOUS CARCINOMA OF COLON – A RARE CASE DIAGNOSED ON HISTOPATHOLOGY

Introduction: Primary Adenosquamous carcinoma is a rare colorectal tumour with both an adenocarcinoma and a squamous cell carcinoma component. To the best of our knowledge, only few cases have been reported in the literature. [2,5] Adenosquamous carcinoma of the colon accounts for 0.02%–0.06% of all colorectal malignant tumours . Case Presentation: We report a case of a 70-year-old woman, hospitalized for acute abdominal pain, fever, vomiting and constipation. Ultrasonography revealed perforated gall bladder. Exploratory laparotomy revealed liver intestinal adhesions, mass lesion in transverse colon and liver abscess. Transverse colon was resected and liver abscess was drained. Resected transverse colon was sent for histopathological evaluation, which revealed Adenosquamous carcinoma of intestine. Patient was discharged after post-op stabilization and sent to higher centre for further treatment. Discussion: Primary Adenosquamous carcinoma is a rare colorectal neoplasm revealed by non-specific complaints. Its clinicopathology is not yet understood. Preoperative diagnosis is often difficult. Surgical resection remains the mainstay of treatment. Primary Adenosquamous carcinoma is a malignant tumour with poorer prognosis than Conclusion: adenocarcinomas. Histopathological evaluation is indispensable for diagnosis of Primary Adenosquamous carcinoma as its clinical presentation is non-specific, so that appropriate treatment can be provided.

RB1-deficient squamous cell carcinoma: the proposed source of combined Merkel cell carcinoma

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine (NE) carcinoma arising from integration of Merkel cell polyomavirus (MCPyV) DNA into a host cell or from ultraviolet light-induced genetic damage (proportions vary geographically). Tumors in the latter group include those with “pure” NE phenotype and those “combined” with other elements, most often squamous cell carcinoma (SCC). We performed comprehensive genomic profiling (CGP) of MCPyV+ and MCPyV− (pure and combined) tumors, to better understand their mutational profiles and shed light on their pathogenesis. Supplemental immunohistochemistry for Rb expression was also undertaken. After eliminating low quality samples, 37 tumors were successfully analyzed (14 MCPyV+, 8 pure MCPyV− and 15 combined MCPyV−). The SCC and NE components were sequenced separately in 5 combined tumors. Tumor mutational burden was lower in MCPyV+ tumors (mean 1.66 vs. 29.9/Mb, P < 0.0001). MCPyV− tumors featured frequent mutations in TP53 (95.6%), RB1 (87%), and NOTCH family genes (95.6%). No recurrently mutated genes were identified in MCPyV+ tumors. Mutational overlap in the NE and SCC components of combined tumors was substantial (‘similarity index' >24% in 4/5 cases). Loss of Rb expression correlated with RB1 mutational (P < 0.0001) and MCPyV− status (P < 0.0001) in MCCs and it was observed more frequently in the SCC component of combined MCC than in a control group of conventional cutaneous SCC (P = 0.0002). Our results (i) support existing evidence that MCPyV+ and MCPyV− MCCs are pathogenetically distinct entities (ii) concur with earlier studies linking the NE and SCC components of combined MCCs via shared genetic profiles and (iii) lend credence to the proposal that an Rb-deficient subset of SCC's is the source of phenotypically divergent combined MCCs.

Aggressive Clinical Deterioration of Recurrent Extramammary Paget’s Disease: A Case Report

Extramammary Paget’s Disease (EMPD) is a rare intraepithelial malignancy of apocrine bearing glands, which occur usually in the perianal region, vulva, scrotum, penis and ax-illa. Most of the disease are treated by surgical resection and the prognosis is generally good. Even though recurrent disease, it is usually slowly progressed with good prognosis. Here we describe the case of a 70-year-old male who has presented with initially just as an EMPD component of squamous cell carcinoma in inguinal skin, but he showed recur-rence of EMPD. The disease has progressed rapidly, finally he died of that EMPD in 2 months of recurrence. The purpose of this study is to report the rare case of fulminant disease course of EMPD after recurrence.

Features of lymph node metastasis depending on intratumoral heterogeneity of non-small cell lung cancer in patients with different morphological changes in the bronchial epithelium

The aim of the study: to examine the relationship between the morphological diversity of non-small cell lung cancer and the frequency of lymph node metastasis in groups of patients with different epithelial conditions in the bronchi adjacent to the tumor. Material and methods. Surgical specimens from 90 patients with non-small cell lung cancer, who were treated in the Thoracoabdominal Department Of The Research Institute Of Oncology Of The Tomsk National Research Medical Center in the period from 2009 to 2017 were studied. The histological type of cancer was determined according to the who classification (2020). Lepidic, acinar, papillary, micropapillary, solid and solitary tumor cells were isolated in the parenchymal component of adenocarcinoma. In the parenchymal component of squamous cell carcinoma, 5 types of structures were distinguished: with keratinization, consisting of atypical cells of the prickly type without keratinization, consisting of atypical cells of the basaloid type, built of atypical cells with pronounced polymorphism, single tumor cells. Results. In patients with isolated basal cell hyperplasia, acinar (37 %), papillary (29 %) and solid (27 %) patterns were found less frequently in cases with metastatic regional lymph nodes compared to those without metastatic lymph nodes (63 %; p=0.05; 71 %; p=0.05; 73 %; p=0.01, respectively). In patients with isolated basal cell hyperplasia of the bronchial epithelium, in cases with the presence of lymph node metastasis in the parenchymal component of squamous cell carcinoma, structures 1 (with keratinization) (17 %), 2 (spiky pattern) (33 %) and 4 (polymorphic pattern) (29 %) were less frequently detected compared to those without metastases in regional lymph nodes (83 %; p=0.01; 67 %; p=0.02 and 71 %; p=0.01, respectively). In patients with a combination of basal cell hyperplasia and squamous metaplasia, a spiny pattern (65 %), a basaloid pattern (100 %), a polymorphic pattern (82 %) and single tumor cells (89 %) were more frequently detected in cases with metastatic lymph nodes than in cases without metastatic lymph nodes (35 %; р=0.04; 0 %; р=0.01; 18 %; р=0.01; 11 %; р=0.01, respectively). Conclusion. The data obtained clarify the available information on the significance of the morphological heterogeneity of the tumor for predicting the course of adenocarcinoma and squamous cell carcinoma of the lung.

The Correlation Between Histologic, Immunophenotypic, and Molecular Characteristics of Pulmonary Sarcomatoid Carcinoma Reveals That Sarcomatoid Change Is Potentially Derived From Epithelial Carcinoma Cells Undergoing Epithelial-Mesenchymal Transition.

Pulmonary sarcomatoid carcinoma (PSC) is characterized by biphasic tumors with epithelial and mesenchymal phenotype. Little is known about the correlation between histologic, immunophenotypic features and the genetic profile of PSC. We analyzed the expression of epithelial-mesenchymal transition-related markers, adenocarcinoma (ADC) and squamous cell carcinoma lineage-specific markers of 205 PSC cases. The alteration of 5 targeted genes was detected by amplification-refractory mutation system-polymerase chain reaction. The intensity of cytokeratin staining was stronger in epithelial carcinoma (EC) than that of the sarcomatoid component (SC) of pleomorphic carcinoma, while vimentin was positive in only 16.3% (17/104) of EC of pleomorphic carcinoma. There is no significant difference between thyroid transcription factor 1 (TTF-1) expression in the SC (46.5%, 33/71) of pleomorphic carcinoma with ADC components and pure PSC (44.2%, 42/95) without p40 expression ( P =0.858). Four cases with ALK rearrangement were confirmed to co-express ALK fusion protein in both the SC and EC. The incidence of EGFR/ALK/KRAS mutation was similar between pleomorphic carcinoma with ADC components (40.6%, 26/64) and TTF-1 + pure PSC (38.2%, 13/34) ( P =0.583). However, higher proportions of TTF-1 + /p40 - PSC patients (44.8%, 39/87) had EGFR/ALK/KRAS mutation than those with TTF-1 - /p40 - PSC (16.7%, 4/24) ( P =0.031). The incidence of EGFR mutation was significantly higher in TTF-1-positive (18.4%, 16/87) than TTF-1-negative (2.7%, 2/74) PSC ( P =0.002). No EGFR and ALK abnormality were observed in 24 pleomorphic carcinoma cases with squamous cell carcinoma components or pure PSC with p40 expression. Our study reveals a close correlation between SC and EC components of pleomorphic carcinoma in terms of immunophenotypic and genetic features, which suggests that pleomorphic carcinoma is potentially derived from the sarcomatoid change of EC cells undergoing epithelial-mesenchymal transition.

237. DIFFERENTIAL CLONAL EVOLUTION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA IN RESPONSE TO NEO-ADJUVANT CHEMORADIOTHERAPY

Abstract As a major component of esophageal squamous cell carcinoma (ESCC) treatment regimen, neo-adjuvant chemoradiotherapy (NCRT) affects ESCC genome is largely unknown. Deciphering the evolutionary history of ESCC following NCRT would reveal dynamic mutational processes and enable us identify the key molecular features associated with NCRT-resistance. We performed whole exome sequencing (WES) on matched pre-NCRT endoscopic biopsy tissue (n = 29), post-NCRT cystectomy tumor tissue (n = 30). On the basis of a rigorous evaluation of estimated percentage of the estimated percentage of vital residual tumor cells, 29 pre-NCRT cases were classified into two groups: major response (n = 20) and minor response (n = 9). The computational method PyClone was used to define subclones within each tumor. The method Clonality Inference in Tumors Using Phylogeny (CITUP) was subsequently used to infer phylogenetic relationships among subclones. By comparing the subclonal composition of each patient before and after NCRT, we found that resistant subclones were polyclonal and driver mutations improved the fitness of resistant subclones. The number of driver mutations existed in resistant subclones was positively related to the size of subclones. The most frequent driver genes in resistant subclones identified in our research included TP53, NOTCH1 and a novel gene RYR3. Multi resistant subclones result in the resistance of ESCC genome to NCRT. The fitness of resistant subclones is relevant to the number of driver mutations.

Novel Correlations among the Histopathological Components of Oral Squamous Cell Carcinoma

Background: Oral squamous cell carcinoma (OSCC) is an aggressive tumor with high mortality and morbidity rates.&#x0D; Aims:In this study, we aimed to probe whether there is association between stromal histopathological parameters with patient data, as well as, the correlation of these parameters with each other.&#x0D; MaterialsandMethods:This study was performed at University of Duhok, College of Dentistry, the practical section was carried out between February 2022 and June 2022 as follow:A group of 86 formalin fixed paraffin embedded (FFPE) samples of OSCC and 20 FFPE samplesof healthy gingiva were stained with Hematoxylin and eosin(H&amp;E) and Mason’s trichrome (MT)stains. Tumor/ stroma ratio(TSR), stromal tumor-infiltrating lymphocytes(sTIL), budding activity (BA), cell nest size (CNS), orientation and packing of collagen fibers and collagen fibercontent(CFC) were evaluated. These histomorphological parameters were correlated with clinicopathological characteristics and with each other.&#x0D; Statistical Analysis Used: Chi square test, fisher exacts test and spearman’s rank correlation coefficient were used for analyzing our study data.&#x0D; Results: Tumor/ stroma ratio, BA, CNS, orientation and packing of collagen fibers, and CFC were significantly associated with pT stage of the tumor. Moreover, significant correlations were observed among TSR, BA, CNS and CFC. In addition, orientation and packing of collagen fibers were significantly correlated with each other.&#x0D; Conclusions: Novel correlations were found between collagen fiber features with TSR, BA, and CNS in an easy and cost- effective methods.

Adenosquamous Carcinoma of Ascending Colon: Where an Unseen is Seen

Colorectal carcinoma is one of the most malignant solid tumors in Western countries. With the exception of the lower rectum, most primary malignant colorectal tumors are adenocarcinomas. The frequency of adenosquamous. carcinoma of the colon is <0.1% . The first case of colorectal adenosquamous carcinoma was reported by Herxheimer in 1907 and was described as a tumor with both adenocarcinoma and squamous cell carcinoma components.