Defined Cell Borders Research Articles

Clinicopathological features of SMARCA4-deficient lung adenocarcinoma: a study of 42 cases

Objective: To investigate the clinicopathological characteristics and genetic mutations of SMARCA4-deficient lung adenocarcinoma. Methods: From January 2021 to April 2023 in the First Affiliated Hospital of Zhengzhou University, 42 cases of SMARCA4-deficienct lung adenocarcinoma were diagnosed and now analyzed. All cases were retrospectively studied using hematoxylin-eosin staining and immunohistochemistry. The clinicopathological features were reviewed. Next-generation sequencing (NGS) was performed to investigate the mutations of related genes. Results: Among the 42 cases, there were 35 biopsy and 7 surgical specimens. There were 38 males and 4 females. The male to female ratio was 9.5∶1.0, with an age range from 42 to 78 years. Thirty-three patients were smokers. Overall, 4 cases (9.5%), 2 cases (4.7%), 18 cases (42.9%) and 18 cases (42.9%) were at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. Microscopically, all the cases were non-mucinous adenocarcinoma, without lepidic pattern. The morphology was diverse. Rhabdomyoid cells, tumor giant cells and tumor necrosis were present. Most of the tumor cells had eosinophilic cytoplasm and occasionally clear cytoplasm. Defined cell borders and variable cytoplasmic hyaline secretory globules could be found. Inflammatory cells infiltrated the tumor stroma. Immunohistochemistry showed 29 cases (69.0%, 29/42) expressed TTF1, 10 cases (40.0%, 10/25) expressed Napsin A, and 20 cases (100.0%, 20/20) expressed INI1. Forty cases (95.2%, 40/42) showed BRG1 loss in all tumor cells, while 2 cases (4.8%, 2/42) had partial BRG1 loss. PD-L1 (22C3) was positive in 59.2% of the cases (16/27). NGS revealed mutations in EGFR, ROS1, MET, RET and KRAS. Six cases (6/8) showed SMARCA4 mutation, while some cases were accompanied by mutations of TP53 (7/15), STK11 (4/8), and KEAP1 (1/8). Driver gene mutations were more common in women (P<0.05). Patients were followed up for 1-25 months. Four patients died and 20 patients' diseases progressed. Conclusions: SMARCA4-deficient lung adenocarcinoma lacks characteristic morphology. Most of them express TTF1 and harbor driver gene mutations. It is necessary to identify this subset of lung adenocarcinoma by carrying out BRG1 stain routinely on lung adenocarcinoma. These patients can then be identified and benefit from targeted therapies.

DIFFUSE ECTOPIC DECIDUOSIS MIMICKING AS PERITONEAL CARCINOMATOSIS: A CASE REPORT OF A YOUNG FEMALE WITH MULTIPLE SEROSAL AND OMENTAL NODULES FOUND DURING A CAESARIAN SECTION

Background &amp; Objectives: Ectopic deciduosis refers to an abnormal occurrence of decidual tissue beyond the endometrium, predominantly on the surface of the uterus, fallopian tubes, ovaries and omentum. Diffuse omental and perito-neal involvement is a perplexing manifestation that may mimic peritoneal carcinomatosis. It is not accompanied by any symptoms and complications in most of the cases and does not require treatment. However, rarely it can present with acute abdomen or imitate peritoneal malignancy and, thus, associated with diagnostic difficulties and unnecessary interventions. Aim of this case report is to describe a rare case of peritoneal deciduosis in a young female, found incidentally, during a caesarean section, mimicking metastatic nodules. Afutile hysterec-tomy along with omentectomy was performed.&#x0D; Methods: A case of diffuse ectopic deciduosis mimicking as peritoneal carcinomatosis in a 29 years young female with full term pregnancy was found during a lower segment caesarian section, undertaken in a tertiary care teaching hospital of Lahore, Pakistan. The histopathological diagnosis was based on common technique of paraffin embedding and hematoxylin-eosin staining along with ancillary immune-histochemical evaluation.&#x0D; Results: Histopathological evaluation showed ectopic decidual tissue consisted of solid nests and loosely cohesive aggregates; large polygonal cells with abundant granular eosinophilic cytoplasm; sharply defined cell borders, bland nuclei with dispersed chromatin and single conspicuous nucleoli on the surface of uterus and in omental fat. Weak staining for CD30 was observed in the decidual cell cytoplasm and negative staining for CK and Calretinin in decidual cells was found. Calretinin and CK highlight benign mesothelial cells and help to rule out differentials of mesothelioma and metastatic carcinoma.&#x0D; Conclusion: Peritoneal deciduosis represents a rare entity and it is important to consider this condition in patients, especially in pregnant women, to prevent unnecessary intervention In addition, distinguishing this condition from malignant neoplasms will help in deciding correct treatment options.

Neurofibroma at an Aberrant Location - A Case Report

Background: Neurofibromas are benign tumors of peripheral nerve sheath and are uncommon in cervical part of vagus nerve. A 35-year female presented with nontender swelling on the left side of the neck since 2 months with no family history. Clinical diagnosis was made as? carotid body tumor/parapharyngeal mass. CT neck showed well defined hypodense oval mass in the left upper neck in the carotid space reported as features suggestive of schwannoma. Post-operative diagnosis of left vagal schwannoma was made and sent for histopathological examination. Gross morphology was well circumscribed grey white mass measuring 6x4x3cms with gelatinous cut surface. On microscopy it was neoplasm composed of spindle cells with poorly defined cell borders having buckled nuclei with pale eosinophilic cytoplasm. These cells are arranged loosely in the background of collagenous matrix. No evidence of atypia or malignancy noted. Features consistent with Neurofibroma. Conclusion: Histopathological confirmation is essential for the diagnosis of neurofibroma in cervical part of vagus nerve as it is an uncommon site for the lesion to develop. Keywords: Neurofibroma, Cervical part of vagus nerve, Aberrant site

Recurrence of adult granulosa cell tumor of the ovary: experience at a tertiary care center

Adult granulosa cell tumor (AGCT) is the most common ovarian sex cord stromal tumor with a favorable prognosis. However, a subset of patients develop recurrence. We retrieved and reviewed 156 cases of AGCT reported between 1992 and 2012. The ages ranged from 20 to 84 years (mean, 48 years). The size of the tumor ranged from 0.8 to 25 cm (mean, 10 cm). Histologically, all tumors were composed of round or polygonal cells with indented or grooved nuclei, eosinophilic cytoplasm, and well defined cell borders. A diffuse pattern was seen in the majority followed by microfollicular, trabecular and macrofollicular. The mitotic figures ranged from 2 to a maximum of 21/10 HPFs. Focal necrosis were seen in 17 cases. Associated simple hyperplasia of endometrium was seen in 9 cases, complex hyperplasia in 2, and endometrioid adenocarcinoma of the endometrium in 3 cases. Recurrence was seen in 8 cases with a follow-up of 2 to 19 years (mean, 6 years). The recurrent tumors were mostly >5 cm and sites included the same adnexal site and contralateral ovary, omentum, mesentery of small bowel, abdominal wall, uterine and fallopian tube serosa, lymph nodes, pelvis, and appendix. Histologically, recurrent tumors exhibited a diffuse histologic pattern and a mitotic count of 6.8 as compared to 3.3 in primary tumors. In conclusion, a tumor size of >5 cm and a diffuse histologic pattern were associated with increased recurrence risk. The recurrent tumors hadz increased mitotic figures compared with primary tumors. Appendix, a very rare site of recurrence was seen in one of our cases.

Cytologic features of triple‐negative breast carcinoma

Triple-negative breast cancer (TNBC) is distinct from other breast cancers, because the tumor cells lack estrogen and progesterone receptors (hormone receptors) and also are negative for human epidermal growth factor receptor 2 (HER2). They comprise a heterogeneous group of tumors with various histologic features and clinical behaviors. High-grade, invasive ductal carcinoma not otherwise specified is the most frequent type, and a substantial fraction of TNBCs belongs to the basal-like tumor type. The purpose of this study was to determine whether some cytologic features could predict the triple phenotype of breast carcinoma. Fine-needle aspiration cytology samples of 62 TNBCs were compared with samples of 82 hormone receptor-positive, high-grade, invasive carcinomas (HRBC) and with samples of 33 hormone receptor-negative, HER2 positive, invasive carcinomas (HER2BC) for the following cytomorphologic features: cellularity, necrosis, lymphocytes, syncytial clusters, tubular/ductal-like clusters, large bare nuclei, streaming within the clusters, and calcifications. Moreover, single cell features, such as cellular borders, cytoplasm, cytoplasmic vacuoles, nuclear pleomorphism, nucleoli, and type of chromatin pattern, were evaluated. Descriptive analyses and 2 multivariate regression models were performed to compare TNBC, HRBC, and HER2BC and to identify the cytologic factors that were associated with tumor type. TNBCs were more likely to have an abundant necrotic background, many lymphocytes, many syncytial clusters, and ill defined cell borders than non-TNBCs. A tubular/ductal pattern was observed only rarely in TNBCs. Multivariate logistic analysis indicated a 90.8% probability of identifying TNBC versus HRBC by the following cytologic variables: lymphocytes, ill defined cell borders and syncytial clusters, tubular/ductal clusters, cytoplasmic vacuoles, and cellular pleomorphism; whereas there was a 77.5% probability of identifying TNBC rather than HER2BC by the following variables: cellularity, ill defined cellular borders and syncytial clusters, and tubular/ductal clusters. Although TNBCs embrace a heterogeneous group of tumors, in this study, they exhibited some common cytologic features that can help to distinguish them from other high-grade breast carcinomas in daily practice.

Symplastic glomus tumor – a rare but distinct benign histological variant with analogy to other ‘ancient’ benign skin neoplasms

A 78-year-old woman presented with a nail deformity of the index finger of the left hand associated with paroxysmal pain upon cold exposure. Histologically, a well-circumscribed tumor of 3 mm diameter was found in the dermis. The neoplastic cells in some areas were of pronouncedly variable size and cytomorphology, mostly epithelioid in shape, with eosinophilic cytoplasm and indistinctly defined cell borders. Pronounced nuclear pleomorphism and atypia were striking features, but no mitotic figures were noted. Multinuclear cells were present as were numerous small-to-medium vessels throughout the tumor. The tumor stroma showed myxoid areas. Immunohistochemistry showed cytoplasmic and membranous expression of smooth muscle actin and vimentin. The histological features and immunoprofile were consistent with the diagnosis of symplastic glomus tumor, a rare histological variant, which has been defined as a glomus tumor exhibiting marked nuclear atypia, in the absence of any other criteria for malignancy. The biological behavior of the tumor is benign. It is essential to differentiate this entity from malignant glomus tumor, which has metastatic potential. Even prominent cellular atypia and nuclear pleomorphism in a glomus tumor as in our case is not a marker of malignancy in the absence of additional criteria.

Primary leptomeningeal oligodendrogliomatosis

Primary leptomeningeal oligodendrogliomas (PLOs) are rare intracranial malignancies where tumors grow in the subarachnoid space without an obvious connection to the brain or spinal cord parenchyma. Adding to the three previously reported cases of PLO with no parenchymal involvement we report a fourth case of the same in this paper in a 50-year-old woman presenting with unrelenting headaches. CT scan of her head revealed hydrocephalus and MRI revealed diffuse enhancement of her leptomeninges throughout her brain and spine, prominent over the basilar region. Biopsy obtained using a frameless stereotactic biopsy showed sharply defined cell borders, clear cytoplasm, and rounded nuclei consistent with an oligodendroglioma. Our case suggests that PLO can mimic diffuse forms of granulomatous meningitis and should be suspected in patients that clinically and radiographically present like granulomatous meningitis but without blood or CSF markers for the same.

Review of the Cytologic Features of Noninvasive Ductal Carcinomas of the Pancreas

Invasive ductal adenocarcinoma (IDA) of the pancreas (IDAP) originating from the ductal gland has a poor prognosis. Noninvasive carcinomas are principally intraductal papillary mucinous carcinomas (IPMCs) and pancreatic intraepithelial neoplasms 3 (PanIN-3). Small papillary-cohesive clusters, individually well-enveloped nuclei in well-preserved cytoplasm, centrally located nuclei, small nuclei (about 10 mum), euchromatin, clearly defined cell borders, small cytoplasm without prominent anisocytosis and no cytoplasm more than 21 mum in shortest diameter, a mixture of goblet cells, and a pleomorphic aspect are common in IPMC and intraductal papillary mucinous neoplasm (IPMN), whereas malignancy in nuclei are observed only in IPMC. PanIN-3 cells have small papillary-cohesive and compact clusters, a monomorphic aspect, and small dense cytoplasm and are highly suggestive of malignancy. IDA cells have loose sheet and solid clusters, poorly preserved cytoplasm, nuclei that tend to adhere to each other, large nuclei, a combination of large nuclei (short diameter <15 mum) with hyperchromatin, a monomorphic aspect, and abundant cytoplasm more than 21 mum in the shortest diameter. To preoperatively differentiate noninvasive IPMC and PanIN-3 from IDAP, these features would be clinically very useful.

Deep Penetrating Nevus in a Combined Nevus

A 46-year-old female appeared with a pigmented lesion on her left cheek that was removed by shave biopsy. The provisional clinical diagnosis was hemangioma. Histologic examination revealed round to spindle cells with poorly defined cell borders in the superficial dermis. The cells tended to group in a thèque-like arrangement in some areas, and melanin pigment was found associated with these cells. Nevus giant cells were occasionally seen. The shave biopsy was signed out as an intradermal nevus. A wider and deeper excision was performed for esthetic purposes, and the histopathology revealed sheets of round to spindle epithelioid cells surrounding adnexal structures and penetrating through the entire thickness of the dermis and into the subcutaneous fat. A vague nestlike growth pattern of these epithelioid cells was seen in some areas, and numerous large melanin-containing cells were identified. Nuclear pseudoinclusions were seen in many of these epithelioid cells. Mitotic figures were rare and no inflammation was seen. A diagnosis of deep-penetrating nevus was rendered. The differential diagnosis and current knowledge on combined nevi will be discussed.

Immunohistochemical Analysis of Embryonal Sarcoma of the Liver

Embryonal sarcoma of the liver is a rare, aggressive malignant tumor that typically occurs in children and teenagers. Microscopic features include spindle, oval, or stellate cells with poorly defined cell borders, nuclear pleomorphism and multinucleation, and variable immunoreactivity to cytokeratin, vimentin, and alpha-1-antitrypsin. Intracellular and extracellular PAS-positive, diastase-resistant hyaline globules are commonly present. The authors evaluated a panel of IHC stains to better define the pattern of immunoreactivity in this tumor. Embryonal sarcomas of the liver were identified from archival files and were immunostained with antibodies: cytokeratin AE1/3, hepatocyte, SMMS, myogenin, calponin, h-caldesmon, desmin, S100, vimentin, CD34, C-kit (CD117), CD10, ALK-1, PE10, Bcl2, p53, and Ki-67. Six cases were identified. Patient age ranged from 6 to 24 years. Tumors ranged from 10 to 20 cm and contained spindled and epithelioid areas with PAS-positive, diastase-resistant globules and atypical cells with focal multinucleation. All cases showed immunoreactivity with vimentin and five showed immunoreactivity with Bcl2. Focal immunoreactivity was seen with cytokeratin AE1/3 in three cases, CD10 in four, calponin in two, desmin in one, and p53 in four. All tumors were negative with hepatocyte, myogenin, CD34, SMMS, h-caldesmon, PE10, ALK-1, and S100. No cytoplasmic staining was seen with C-kit. The proliferation index ranged from 30% to 95%. The diagnosis of embryonal sarcoma is based on typical morphologic features in a large liver tumor occurring in a young patient. The most useful IHC stains help to exclude tumors such as hepatoblastoma, hepatocellular carcinoma, embryonal rhabdomyosarcoma, and other sarcomas.

A 70-Year-Old Man With Multiple Intra-abdominal Masses and Liver and Spleen Metastases

The biopsy core was 1.2 cm in length. Microscopically, spindle cells were arranged in short intersecting fascicles and a vague storiform pattern with some lymphocytic infiltrate (Figure 2, a). These spindle cells had oval and vesicular nuclei, inconspicuous nucleoli, and eosinophilic cytoplasm with poorly defined cell borders (Figure 2, b). There was no significant cellular atypia, mitotic activity, or necrosis. Immunohistochemically, tumor cells expressed CD21 (Figure 2, c), CD35 (Figure 2, d), and epithelial membrane antigen but not CD1a, CD3, CD20, CD23, CD68, smooth muscle actin, desmin, ALK-1, S100 protein, and Epstein-Barr virus (EBV) latent membrane protein 1. The proliferation fraction as determined by Ki67 was 10%. These tumor cells and the small lymphocytes were both negative for EBV-encoded mRNA as indicated by in situ hybridization. These small lymphocytes were mainly CD3-positive T cells with a proliferation fraction at 10%, and the majority expressed CD8, T-cell intracytoplasmic antigen, and granzyme B. What is your diagnosis?

Spindle-Cell Epithelioma: “Mixed Tumor” of the Vagina

Spindle-Cell Epithelioma: “Mixed Tumor” of the Vagina

The effect of butyrate on sulfated glycoprotein biosynthesis by human kidney tumor cells.

Human kidney tumor cells in culture incorporate [3H]glucosamine and 35SO4 into several classes of glycoconjugate products. After a 24-h labeling period, the 3H/35S-glycosaminoglycans and 3H-glycoproteins synthesized were found associated with both the cell layer and the culture medium. These tumor cells also synthesized a class of 35S-glycoproteins which contained alkali-stable 35S-oligosaccharide chains. These 35S-glycoproteins did not accumulate with the cell layers but were preferentially found in the culture medium (82-96%). After treatment with 2.5 mM butyrate for 24 h, the tumor cells assumed a more flattened and spread morphology with more clearly defined cell borders. These butyrate-treated cell cultures showed less than a 2-fold increase in the cell-associated form of both 3H/35S-glycosaminoglycans and 3H-glycoproteins, compared to cells cultured in the absence of butyrate. In contrast, butyrate-treated cell cultures had a 3-fold increase in the total incorporation of 35SO4 into glycoproteins and a dramatic 10-30-fold increase in the cell-associated form of these 35S-glycoprotein products as compared to untreated cell cultures.