Low Ki-67 Proliferation Index Research Articles

Abstract PO5-27-12: TALL CELL CARCINOMA WITH REVERSED POLARITY: A RARE SUBTYPE OF INVASIVE BREAST CARCINOMA WITH UNUSUAL ONCOGENIC DRIVER MUTATION R132C IN IDH1 GENE

Abstract Introduction: Tall cell carcinoma with reversed polarity (TCCRP) is a rare subtype of invasive breast carcinoma with a distinguishing morphogical feature, which is the predilection of nuclei to polarize to the apical pole of tall columnar epithelial cells. These tumours are most commonly associated with IDH2 p.Arg172 hotspot mutations. All reported cases of TCCRP affected women ranging from 39 to 89 years (mean age of 64 years). The tumours presented as a mammographic or palpable mass, only rarely associated with axillary lymph node metastases. TCCRP are usually associated with an indolent clinical course and a favourable prognosis. Morphologically, TCCRP is composed of circumscribed nests of epithelial cells often exhibiting delicate fibrovascular cores, conveying a solid papillary pattern. True papillae and cystic structures containing colloid-like material may be observed in some cases. The tumour cells are tall and columnar, with abundant eosinophilic cytoplasm, containing bland, round to ovoid nuclei disposed at the apical pole of the columnar epithelial cells. Mitotic figures are rare. Most TCCRPs exhibit a triple-negative phenotype and a low (< 20%) Ki-67 proliferation index. Molecular features of TCCRP comprise IDH2 p.Arg172 hotspot mutations, reported in about 84% of the cases studied, as well as PIK3CA missense mutations, identified in about 68% of these tumours. Only one case of TCCRP was associated with IDH1 gene mutations according to the literature. Case report: A 62 year old woman presented with a palpable mass and no axillary adenopathy was identified. Hematoxylin-eosin (HE) stain showed an invasive breast carcinoma, with epithelial tumour cells arranged in a solid and papillary pattern with thin fibrovascular cores. Neoplastic cells are tall and columnar, with abundant eosinophilic cytoplasm and round to ovoid nuclei, exhibiting no pleomorphism and disposed in the apical pole of the cells. Mitotic figures were not detected. Considering the highly suggestive morphology on HE stain, biopsy sample was sent for molecular analysis by next generation sequencing (NGS). Results and discussion: Molecular analysis by NGS using the TruSight Oncology 500 panel (Illumina) revealed the presence of the oncogenic mutations R132C and H1047R in IDH1 and PIK3CA genes, respectively. Contrary to what occurs in almost all cases of Tall cell carcinoma with reversed polarity (TCCRP), in which an oncogenic mutation is described in codon R172 of the IDH2 gene, in this case a mutation was observed in the IDH1 gene. Such a mutation has been described in only one case diagnosed with TCCRP according to the literature, this being the second reported case. Conclusion: This case report aims to warn of the possibility that other driver mutations may be associated with the diagnosis of TCCRP, such as IDH1 R132 and not just IDH2 R172, and that a comprehensive testing approach of the IDH1/2 genes might be more accurate in these cases. Citation Format: Karla Prigenzi, Luiz Gustavo Ferreira Cortes, Paulo Vidal Campregher, João Bosco de Oliveira Filho, Nestor Andrade Piva. TALL CELL CARCINOMA WITH REVERSED POLARITY: A RARE SUBTYPE OF INVASIVE BREAST CARCINOMA WITH UNUSUAL ONCOGENIC DRIVER MUTATION R132C IN IDH1 GENE [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-12.

Primary Well-Differentiated Neuroendocrine Tumor/Carcinoid of the Prostate: Case Report and Review of Literature.

Primary well-differentiated neuroendocrine tumor (WDNT)/carcinoid of the genitourinary tract is rare. Many WDNT reported in the prostate gland have been seen in close association with conventional prostatic adenocarcinoma and/or label for prostate-specific immunohistochemical markers and are best considered prostatic adenocarcinomas with "carcinoid-like" features. We present a case of primary WDNT/carcinoid incidentally detected in a 67-year-old man who underwent radical prostatectomy for Grade group 2 prostatic adenocarcinoma. Morphologically, the neuroendocrine (NE) lesion appeared distinct from the prostatic adenocarcinoma, labeled for NE markers, was negative for prostatic markers (NKX3.1, PSA, and ERG), and showed an overall low Ki-67 proliferation index (<1%). Follow-up was uneventful with no evidence of residual disease or metastasis.

Nuclear size and pleiomorphism of breast cancer cells at high and low Ki-67 proliferation index

Background: Breast cancer cells are characterized by enlargement of nuclei and variation of nuclear size. The more anaplastic of cell nuclei reflect more aggressive and malignant cells that affect increase proliferation rate. The aim of this study is to reveal whether there was any difference of anaplastic characteristic of breast cancer cells in high and low degree of proliferation rate. Material and Methods: Twenty-three cases of breast cancer were collected from archive of Pathology Department composed of high and low Ki-67 proliferations index. Anaplastic characteristics of cancer cells were obtained by measuring the area and pleomorphism of breast cancer cells in cytologic specimen from aspiration biopsy material. Result and Discussion: There were no differences between breast cancer cells’ size between high and low Ki-67 proliferation index while there was a difference pleomorphism between high and low Ki67. Conclusion: The degree of anaplasia in breast cancer cells has a relationship with cancer cells proliferation. Further research should be made to reveal the mechanism of this phenomenon.

Assessment of Ki-67 expression levels in IDH-wildtype glioblastoma using logistic regression modelling of VASARI features.

To investigate the value of using VASARI signs preoperatively to assess Ki-67 proliferation index levels in patients with IDH-wildtype glioblastoma (GB).Pathological and imaging data of 154 patients with GB confirmed by surgical pathology were retrospectively analysed, and the level of Ki-67 proliferative index was assessed in tumour tissue samples from patients using immunohistochemistry (IHC) staining. Patients were divided into a high and low Ki-67 proliferation index expression group. Two radiologists analysed MRI images of patients with IDH-wildtype GB using the VASARI features system. VASARI parameters between the two groups were statistically analysed to identify characteristic parameters with significant differences and their predictive performance was determined using ROC curves.Among the obtained clinical and VASARI features of IDH-wildtype GB patients, the distribution of Maximum diameter, Proportion of necrosis and Hemorrhage was significantly different between the two groups (all p < 0.05). Multivariate logistic regression analysis showed that Maximum diameter and Hemorrhage were independent risk factors distinguishing the group with high and low expression of Ki-67 proliferative index. ROC curve analysis showed that the logistic regression model achieved an AUC value of 0.730 (95% CI: 0.639, 0.822), sensitivity of 0.628 and specificity of 0.756.Logistic regression modelling of preoperative VASARI features can be used as a reliable tool for predicting the level of Ki-67 proliferative index in IDH-wildtype GB patients, which can help in preoperative development of treatment and follow-up strategies for patients.

EBV positive plasmacytoma in immunocompetent patients: A diagnostically challenging rare entity

Abstract Introduction/Objective Epstein-Barr Virus (EBV)-positive plasmacytoma is a rare entity that shows morphological and immunophenotypic overlap with plasmablastic lymphoma and can cause a diagnostic dilemma. Here we discuss a unique case of EBER-positive plasmacytoma arising from nasal polyps. Methods/Case Report A 61-year-old immunocompetent male presented with nasal polyps, right maxillary sinus lesions, and an enlarging sternal lesion. Multiple biopsies were obtained which revealed a diffuse infiltration by atypical plasma cells, that were positive for CD138, MUM1, CD79a, CD56, lambda-in situ hybridization, and Ki67- proliferation index of 20-30%. In situ, hybridization for EBV-encoded viral RNA (EBER) was positive in the neoplastic cells. B- and T- cell markers were negative. The flow cytometry studies detected monotypic lambda-restricted CD38/CD138 positive plasma cells with an aberrant expression of CD56 and CD117. Molecular studies for B-and T- cell gene rearrangement were also negative. A final diagnosis of EBER-positive plasmacytoma was made. The patient was treated with cyclophosphamide, vincristine, doxorubicin, and carboplatin followed by four cycles of RVD, and is doing well. Results (if a Case Study enter NA) NA Conclusion EBER-positive plasmacytoma poses a diagnostic challenge with plasmablastic lymphoma, specifically in immunocompetent individuals. The useful differentiating clues pointing towards EBER positive plasmacytoma could be a spectrum of morphology ranging from mature to anaplastic, low Ki67 proliferation index, aberrant CD56 and CD117 positivity, and high M- spike on protein studies. Comprehensive clinical, morphologic phenotypic, and genetic investigations are necessary to make a specific diagnosis as the two entities differ in their management.

A Rare Case of Incidental Primary Follicular Lymphoma Co-Existing With Grade Group 5 Prostatic Adenocarcinoma

Abstract Introduction/Objective Primary lymphoma of the prostate is an exceedingly rare entity comprising less than 0.1% of all prostatic cancers with follicular lymphoma making up only 12% of primary prostatic lymphomas. There is very limited literature owing to their rarity and underdiagnosis. To the best of our knowledge, prostatic adenocarcinoma with an incidental follicular lymphoma presenting as a prostate imaging reporting and data system 4 (PI-RADS 4) lesion on multiparametric magnetic resonance imaging (mpMRI) with mildly elevated serum prostate specific antigen (PSA) has not been previously described. Methods/Case Report A 73 year old male presented to Danbury Hospital for follow up on benign prostatic hyperplasia (BPH) diagnosed in 2020. The patient was experiencing nocturia and had a serum PSA of 4.8. Multiparametric MRI revealed an enlarged, 5.5 x 4.1 x 3.3 cm, prostate gland (estimate weight of 45.5 grams) with a 1.2 cm PI-RADS 4 lesion in the right anterior mid gland. There was no evidence of metastatic disease on his most recent body imaging. He was subsequently scheduled for prostate needle biopsy. Histopathology showed a high grade prostatic adenocarcinoma, with a Gleason score 4 + 5=9, along with a focally prominent dense lymphoid infiltrate in four of four cores from the same area of abnormality that was detected on mpMRI. The latter comprised of ill defined follicles and sheets of small cleaved atypical lymphoid cells consistent with centrocytes and very few centroblasts. By immunohistochemical staining, the atypical cells in lymphoid follicles and interfollicular areas were positive for CD20, CD10 and BCL2 and negative for cyclin D1. CD21 stain highlighted the follicular dendritic cell meshwork in the germinal centers with a low Ki67 proliferation index. A final diagnosis of low grade follicular lymphoma (grade1-2) coexisting with the prostatic adenocarcinoma was rendered. The patient is currently undergoing lymphoma staging as the treatment for adenocarcinoma is planned. Results (if a Case Study enter NA) NA Conclusion Primary lymphoma of the prostate usually presents with non specific obstructive voiding symptoms and normal or near normal PSA levels which makes it challenging for physicians to suspect lymphomas. The lymphocytic infiltrate, originally thought to be prostatitis, underwent further evaluation with immunohistochemistry due to its monotonous appearance, which clinched the final diagnosis. Careful evaluation of prostate core needle biopsies is necessary even after spotting carcinoma in order to rule out low grade lymphomas.

Concurrent metastatic melanoma and follicular lymphoma diagnosis on liver fine needle aspiration and biopsy

Abstract Introduction/Objective The liver is commonly involved in metastatic neoplasms, such as colorectal, breast, esophageal, stomach, pancreatic, lung, and kidney. Fine needle aspiration (FNA) and core needle biopsy (CNB) are frequently used to establish an accurate diagnosis of liver masses. Here we report the coexistence of metastatic malignant melanoma (MM) and follicular lymphoma (FL) involving the liver. To our knowledge, This is the first reported case, and we hope to add to the literature. Methods/Case Report The patient is a 75 -year-old woman diagnosed with stage I skin melanoma in 2004, and systemic low-grade FL in 2009. She presented with fatigue, weight loss, and difficulty swallowing. CT scan showed new pulmonary, hepatic, and splenic nodules with stable abdominal lymphadenopathy. Smears from the liver nodule FNA showed numerous single tumor cells with moderate cytoplasm and eccentrically located hyperchromatic nuclei. CNB showed fragments of liver parenchyma infiltrated by metastatic melanoma and a focal portal area with expansile lymphoid aggregates of small lymphocytes. The lymphoid cells were positive for CD10, CD20, PAX5, and BCL2 and negative for CD3, CD5, BCL6 and BCL1, with a low Ki-67 proliferative index (&amp;lt;5%). Although not characteristic of an FL, this immunophenotype was most consistent with FL given her clinical history. The metastatic MM was positive for SOX10 and Melan-A, while negative for CD45 and CK AE1/AE3. Despite neoadjuvant therapy, the patient died just two months after diagnosis. Results (if a Case Study enter NA) NA Conclusion A tremendous variety of neoplasms can occur in the liver. Different morphologies under a microscope should broaden the list of differential diagnoses. Familiarizing with morphological features and using ancillary studies are essential for accurate diagnosis and proper patient management. FNA and CNB combined with ancillary studies can successfully establish the diagnosis of malignancies involving the liver.

Intramuscular capillary-type hemangioma: Diagnosis, treatment, and outcomes. A French multicentric retrospective study of 66 cases

PurposeIntramuscular capillary-type hemangiomas (ICTHs) are rare entities, belonging to the group of intramuscular “hemangiomas.” The diagnosis remains challenging. We aimed to assess the diagnostic criteria, treatments and outcomes of ICTHs. MethodsThis retrospective study collected all cases of ICTH followed up in 9 French hospital centers, reviewed by an adjudication expert group. ResultsAmong 133 patients screened, 66 with ICTH were included. The median age of patients at diagnosis was 28.0 years, interquartile range (21.0–––36.0). The lesion, mainly presenting as a gradually increasing mass (83.9%), was painless (88.9%) and was located in the head and neck (42.4%). MRI (available in all cases) mainly revealed a well-delineated lesion, isointense to the muscle on T1-weighted images, with enhancement after contrast injection; hyperintense on T2-weighted images; and containing flow voids. Among the 66 cases, 59 exhibited typical ICTH features and 7 shared some imaging features with arteriovenous malformations. These latter were larger than typical ICTHs and more painful and appeared on imaging as less well delimited and more heterogeneous tissue masses, with larger tortuous afferent arteries, earlier draining vein opacification and mild arteriovenous shunting. We propose to name these lesions arteriovenous malformation (AVM)-like ICTH. Pathological reports were similar in typical and AVM-like ICTH, showing capillary proliferation with mainly small-size vessels, negative for GLUT-1 and positive for ERG, AML, CD31 and CD34, with low Ki67 proliferation index (<10%), and adipose tissue. The most frequent treatment for ICTH was complete surgical resection (17/47, 36.2%), preceded in some cases by embolization, which led to complete remission. ConclusionsICTH can be diagnosed on MRI when it is typical. Biopsy or angiography are required for atypical forms.

Understanding Glomangiopericytoma: A Case Report of a Rare Sinonasal Tumor

Introduction: Glomangiopericytoma (GPC) is a benign neoplasm of the sinonasal tract that consists of spindle-shaped to ovoid cells with lobular or nodular growth patterns. GPCs are low-malignant tumors due to limited mitotic activity and atypia, making them less aggressive. The etiology of GPC remains unknown but is associated with factors like steroid use, past trauma, pregnancy, and hypertension. GPC is more common in women and is usually diagnosed in the sixth and seventh decades of life. Case Presentation: This article presents a case of a 47-year-old woman with a history of type-2 diabetes and nasal obstruction who was diagnosed with glomangiopericytoma (GPC), a rare sinonasal tumor. Computed tomography revealed a vascular mass, and complete surgical resection was achieved via a trans-nasal approach. The diagnosis was confirmed through positive β-catenin staining and negative S100p and STAT6 with a low Ki67 proliferation index. The patient experienced post-operative pain, anosmia, and ageusia, which were treated successfully. This case highlights the clinicopathologic characteristics, clinical and therapeutic aspects, surgical interventions, and differential diagnosis of GPC, a rare disease with limited reports. Conclusion: Glomangiopericytomas are benign sinonasal tumors often mistaken for other neoplasms. Diagnosis is challenging but possible through excision or biopsy with histopathological examination. Endoscopic surgery with follow-up is the recommended treatment, with recurrence occurring up to 12 years post-surgery. CTNNB1 gene mutations and β-catenin nuclear expression are recent diagnostic markers. GPC has a high survival rate and low metastasis, but patients should be closely monitored. This case report underscores the importance of comprehensive diagnosis and management for these rare tumors.

Abstract #1406235: Silent Corticotroph Adenomas are More Aggressive than Other Nonfunctional Pituitary Adenomas

Silent corticotroph adenomas (SCAs) are immunopositive for adrenocorticotropic hormone (ACTH) but do not cause Cushing disease. They account for approximately 20% of all corticotroph adenomas and 5% of nonfunctioning pituitary adenomas (NFAs). We present a case of an SCA with extensive invasion outside the sella turcica and causing pathology through mass effect on adjacent structures. A 48-year-old male was found to have a 3.8 cm pituitary mass with invasion of the left cavernous sinus and compression of the optic chiasm during an evaluation of headaches and diplopia. No signs of Cushing syndrome or acromegaly were apparent on examination. Metabolic evaluation was notable for secondary hypothyroidism (TSH 0.7 mIU/L, 0.45-5.33; free T4 0.3 ng/dL, 0.5-1.3) and hypogonadism (LH 2.2 mIU/L, 1.2-8.8; total testosterone 105 ng/dL, 270-1070), though serum prolactin (17.3 ng/mL, 2.6-13.2) and IGF-1 levels (133 ng/mL, 71-224) were unremarkable. ACTH level was increased on multiple measurements (69.9-146.8 μg/dL, 7.2-63.3), but 8 AM cortisol level during an overnight dexamethasone suppression test was only modestly elevated (1.9 μg/dL, expected < 1.8). The patient underwent transsphenoidal surgery (TSS) to remove accessible tumor and relieve symptoms of mass effect. Histopathology was notable for a pituitary adenoma with low Ki-67 proliferation index (< 5%) and 70-80% staining for ACTH. Symptoms recurred approximately 1 y later, and imaging revealed a substantial increase in volume of residual tumor. Unfortunately, the patient died from arterial bleeding during a second attempt at TSS. SCAs are more aggressive than NFAs that fail to stain for an intact pituitary hormone. Patients with SCAs are younger, more likely female, and have a greater likelihood of symptoms at diagnosis than patients with NFAs, though the proportion of SCAs present with extrasellar extension is equivalent to NFAs. SCAs and NFAs progress or recur at the same rate, but time to recurrence for SCAs is more than two-fold faster than for NFAs. Recurrence rate and time to recurrence for SCAs are unaffected by adjuvant radiation. SCAs with extensive staining for ACTH as in this case are more likely to be aggressive than tumors with limited staining for ACTH. Reduced expression of the mismatch repair gene MSH 6/2 may be a driver for the behavior of SCAs. This case illustrates SCAs are a small but challenging subset of NFAs with greater propensity to cause symptoms of mass effect and recur quickly than the typical NFA. Extensive ACTH staining is a poor prognostic sign for tumor recurrence.

The prognostic significance of non-lymphoid immune cells of the tumor microenvironment, including neutrophils, eosinophils, and mast cells in breast carcinomas

Background and objectiveThe prognostic importance of lymphoid cells in the tumor microenvironment and their effect on treatment response have been demonstrated in many cancer types. However, there are limited studies on non-lymphoid immune cells. Conflicting results have been obtained regarding the effects of these cells on prognosis. Materials and methodsA total of 331 patients who underwent surgery for breast cancer were included. Patients that received neoadjuvant chemotherapy and those with distant metastasis were excluded. CD 15 immunohistochemistry was performed to detect tumor-infiltrating neutrophils (TINs) and eosinophils (TIEs), while Toluidine Blue histochemistry was performed to detect tumor-infiltrating mast cells (TIMs). ResultsHigh TINs were statistically associated with low ER expression (p < 0.001), low PR expression (p = 0.001), high Ki-67 proliferation index (p = 0.008), and HER2/TN molecular subtypes (p = 0.001). High TIEs were associated with low ER expression (p = 0.001), high Ki67 proliferation index (p = 0.005), and HER2/TN molecular subtype (p = 0.002). High TIMs were associated with high PR expression (p = 0.024), low Ki-67 proliferation index (p = 0.003), and high survival rate (p = 0.006). TIMs and TIEs were good prognostic factors for overall survival in Luminal A and Luminal B subtypes, while TINs and TIEs were found to be independent risk factors for disease-free survival. ConclusionThe evaluation of components of the tumor microenvironment including TINs, TIEs, and TIMs is easy and practical. High TIMs and TIEs are independent prognostic factors, especially in luminal molecular subtype of invasive breast carcinoma. However, to use this parameter in routine pathology practice, more studies from different centers and standard evaluation are needed.

Two Cases of Duodenal Neuroendocrine (Carcinoid) Tumor Concurrent with Invasive Gastric Adenocarcinoma and Pancreatic Intraductal Papillary Mucinous Neoplasm

Abstract Introduction/Objective Neuroendocrine (carcinoid) tumors of the duodenum are extremely rare and account for only 2-4% of gastrointestinal tract neuroendocrine tumors. We report two cases of incidentally discovered duodenal neuroendocrine tumor which respectively occurred in a patient with invasive gastric adenocarcinoma and in a patient with pancreatic intraductal papillary mucinous neoplasm (IPMN). Methods/Case Report The first case involved a 60-year old male who presented with melena and symptomatic anemia and was found on EGD to have a large circumferential mass at the gastric antrum/pylorus, which was revealed to be an invasive gastric adenocarcinoma on biopsy. At the time of distal gastrectomy for this malignancy, a concurrent, 0.6 cm-sized, low grade neuroendocrine tumor was incidentally discovered at the duodenal margin. The duodenal tumor consisted of nests and trabeculae of monotonous cells with ovoid/round nuclei, finely speckled “salt and pepper” chromatin, and low mitotic rate (&amp;lt; 2 mitoses/2 mm2), and invaded only into submucosa. The tumor cells were strongly and diffusely positive for neuroendocrine markers chromogranin, synaptophysin, and CD56, positive for CK7 and CDX2, negative for CK20, and with low Ki67 proliferation index (&amp;lt; 3%). The second case involved a 69-year old female who presented with epigastric pain and was found on abdominal CT to have a 4 cm-sized cystic mass in the pancreatic head. While biopsy of the pancreatic mass revealed an IPMN, a separate biopsy of an incidentally discovered, 1 cm-deep ulcer in the duodenum bulb revealed a low-grade neuroendocrine tumor with similar morphologic features, mitotic rate, and immunohistochemical staining pattern as the prior case while also negative for IMP3 stain. The patient had normal serum gastrin and urine HIAA levels, but elevated serum chromogranin-A levels. Results (if a Case Study enter NA) NA. Conclusion Duodenal carcinoids are rare (1-3% of primary duodenal tumors) and are mostly non-functional and unifocal. The duodenum is also the least common site (2-4%) for GI tract neuroendocrine tumors. The pathophysiology of these tumors is still poorly understood, with the majority occurring sporadically and a minority in the setting of hereditary cancer syndromes. This report documents two very rare instances of duodenal neuroendocrine tumor incidentally discovered with invasive gastric adenocarcinoma and pancreatic IPMN.

Superficial myofibroblastoma of the lower female genital tract: A clinicopathological analysis of 15 cases

ObjectiveTo describe the clinicopathological features and differential diagnoses of 15 cases of superficial myofibroblastoma, a rare mesenchymal tumor involving the lower female genital tract. MethodsThe clinicopathological data and immunohistochemical findings were retrospectively analyzed in 15 cases of superficial myofibroblastoma. Meanwhile, a systematic literature review was conducted. ResultsThe age of patients ranged from 34 to 73 years (median, 49 years). Most patients presented with nodular or polypoid masses ranging in size from 0.4 cm to 6.5 cm. Twelve tumors were located in the vagina, two in the vulva, and one in the cervix. Microscopically, the tumor was located in the subepithelial tissue, with a clear boundary and without capsule on the surface. The tumor cells were spindle, oval, stellate or wavy, and arranged in various architectural patterns of reticular, fascicular, wavy and disorderly patterns. There were no obvious cellular atypia and mitotic figures. Thin collagen fibers and thin-walled vessels could be observed in all cases. Most cases were diffusely and strongly reactive to Vimentin (12/12), Desmin (14/15), ER (15/15) and PR (13/14). Variable immunoreactivity for CD34 (8/15), Caldesmon (2/8), SMA (4/14) and CD99 (4/5) were observed. The tumors showed a low Ki67 proliferative index (≤5 %). Follow-up information was available in 10 patients and there was no evidence of recurrence or metastasis. ConclusionsSuperficial myofibroblastoma is a rare benign tumor that originates from the hormone-sensitive, subepithelial mesenchymal tissue of the lower female genital tract, and should be differentiated from other mesenchymal tumors.

Morphological Features and Immunohistochemical Profiling of Male Breast Gynaecomastia; A Large Tissue Microarray Study.

IntroductionGynaecomastia is the commonest male breast condition accounting for approximately 85% of male breast lesions. There is minimal information on the immunohistochemical profile of gynaecomastia. We aimed to comprehensively profile a large series of gynaecomastia samples for putative mammary diagnostic, predictive and prognostic markers.MethodsA total of 156 samples, were histologically reviewed, assembled onto tissue microarrays, and stained for oestrogen receptors (ERα, ERβ1, ERß2), progesterone receptors (total PR, PRα), androgen receptor (AR), basal & luminal cytokeratins (CK5/6, CK14, CK8/18) and the proliferation marker Ki67. Relevant cut offs for marker positivity were defined based on existing literature: AR (10%), ERα and PR (Allred score >3/8), ERß (10% and 20%), cytokeratins (10%) and Ki67 (10% and 20%).Results108 samples from 86 patients aged 13-75 years were available for immunohistochemical assessment. 73.1% of the lesions were AR positive, compared to 99% for ERα and 100% for both ERß1 and ERß2. 98% of samples were positive for total PR and 97.1% for PRα. 69.8% expressed CK5/6 whilst 57% were CK14 positive. A tri-layered pattern of cytokeratin expression was also observed. Ki67 positivity was low with 17.1% and 6.7% classified as Ki67 positive using 10% and 20% cut off values respectively. A significant negative correlation was found between ERα expression and patient age (rs = -0.221, p=0.023). Bivariate correlations were produced, and comparisons made with previously published data regarding the immunohistochemical status in normal female breast tissue, proliferative and neoplastic breast diseases of the female and male breast.ConclusionsHormone receptors, including oestrogen receptor α and ß isoforms as well as androgen receptors were abundantly expressed within the intraductal luminal hyperplastic epithelium in gynaecomastia supporting the hormonal role in the pathogenesis and treatment. ERα, ERβ1 and ERβ2 were expressed in a higher proportion of cells compared with their expression in the female breast benign lesions which further characterises gynaecomastia biology. The identification of a low Ki67 proliferative index and the mixed cytokeratin profile in gynaecomastia differentiates this benign condition from male breast cancer. Therefore, Ki67 and cytokeratins can help in the differential diagnosis from histological mimics in the routine diagnostic work up.

A PULMONARY PAPILLARY ADENOMA IN A FILIPINO FEMALE: A CASE REPORT AND LITERATURE REVIEW

TYPE: Case Report TOPIC: Lung Pathology INTRODUCTION: Pulmonary papillary adenomas (PPA) are extremely rare tumors with only 31 reported cases in literature. We present the 32nd case of a PPA in a patient presenting with hemoptysis. CASE PRESENTATION: A 23-year-old female with no comorbidities consulted for hemoptysis approximately 100cc in amount. Physical examination was unremarkable. CBC and bleeding parameters were normal. Chest radiograph revealed a left retrocardiac ovoid opacity and a contrast chest CT revealed a well-circumscribed enhancing mass in the left lower lobe measuring 2.5 x 3.2 x 2.6cm. Percutaneous needle biopsy of the lung mass revealed tumor cells forming papillary structures with fibrovascular cores lined by a single layer of cuboidal to low columnar epithelium, without nuclear atypia or mitotic activity. Immunohistochemically, TTF-1 and Napsin-A showed strong, diffuse positivity in the surface epithelial cells, with a low Ki-67 proliferation index, expressed only in 5-10% of the cells. The primary consideration is a pulmonary papillary adenoma. Further immunohistochemistry is essential to rule out other entities that may present similarly. The patient underwent a video-assisted thoracoscopic left lower lobectomy with no complications thereafter. DISCUSSION: The 31 existing cases in literature were reviewed, most are asymptomatic and are only incidentally seen on imaging. They are more commonly found in the lung periphery, usually in the lower lobes. Majority of patients are treated surgically without any recurrence or complications. CONCLUSIONS: PPAs are rare neoplasms. Biopsy and immunohistochemical staining are essential in their diagnosis and must be advocated in the work-up for patients with lung masses. DISCLOSURE: Nothing to declare. KEYWORD: papillary adenoma

Impact of tumor size and location on endoscopic ultrasound-guided sampling of pancreatic neuroendocrine tumors: A recursive partitioning analysis

BackgroundCurrent guidelines provide weak recommendations to treat small (<2 cm) non-functional pancreatic neuroendocrine tumors with low Ki-67 proliferation index either by resection or clinical follow-up. However, there is a lack of consensus regarding the minimal size of pNET, which allows EUS-guided biopsy with high enough diagnostic accuracy for stratification. MethodsWe conducted a retrospective, bicentric analysis of patients who had undergone EUS-guided pNET sampling in two tertiary care Endoscopy Units in Germany and Poland. Using a recursive partitioning of the tree-aided model, we aimed to stratify the probability of successful EUS-guided biopsy of pNET lesions according to their size and location. ResultsIn our pNET cohort, successful histological confirmation of a pNET diagnosis was achieved in 59/69 (85.5%) cases at the initial EUS-guided biopsy. In 41 patients with a pNET size less than 18.5 mm, the EUS-guided first biopsy was successful in 90.2%. In 16 of these patients with smaller lesions, EUS-guided sampling was 100% in very small (less than 11 mm) and extremely small lesions (less than 8 mm). The biopsy success rate was 100% in tail lesions in the size range between ≥5.95 and <8.1 mm but only 33.3% independent of the investigator in pancreatic head or body, with an error rate of 11.2% ConclusionUsing a recursive partitioning of the tree-aided stratification model, we demonstrate for the first time that in balancing risks and benefits, very small pNETs (<1 cm) in the tail of the pancreas should be sampled under EUS-guidance.

Minimal apparent diffusion coefficient in predicting the Ki-67 proliferation index of pancreatic neuroendocrine tumors.

To investigate the diagnostic performance of the minimal apparent diffusion coefficient (ADCmin) to distinguish between pancreatic neuroendocrine tumors (Pan-NETs) with low and high Ki-67 proliferation index values and to evaluate the relationship between ADCmin and the Ki-67 proliferation index. Pre-operative magnetic resonance imaging data and postoperative Ki-67 proliferation index data of 42 patients with primary neuroendocrine tumor of the pancreas from November 2014 to March 2021 were included in this retrospective study. According to the Ki-67 proliferation index value, Pan-NETs were divided into a high-expression group (Ki-67 ≥ 10%, n = 17) and low-expression group (Ki-67 < 10%, n = 25), and mean ADC (ADCmean) and ADCmin values were compared between groups using receiver operating characteristic (ROC) curves to evaluate the performance of ADCmean and ADCmin in judging the expression level of Ki-67 proliferation index. The relationship between ADCmin and the Ki-67 proliferation index was also evaluated. The ADCmin was significantly higher in the low-expression group (Z = - 3.537, p < 0.01). The area under the ROC curve (AUC) for ADCmin was 0.825, which was higher than that for ADCmean (0.781). Using 1.32 × 10-3 mm2/s as the optimal discriminating threshold, the sensitivity, specificity, accuracy, and positive and negative predictive values of the two groups were 80%, 88.2%, 83.3%, 90%, and 75%, respectively. The ADCmin of Pan-NETs showed a significant negative correlation with the Ki-67 proliferation index (rs = - 0.634, p < 0.001). The ADCmin is a potential imaging biomarker, which may be helpful for non-invasive preoperative prediction of the Ki-67 proliferation index of Pan-NETs and the subsequent planning of appropriatetreatment.

Clinicopathological and immunohistochemical analysis of plasma cell gingivitis- A retrospective study.

This study aims to describe the demographics and clinicopathological characteristics of the cases of plasma cell gingivitis (PCG) reported in our institute, supported by a review of pertinent literature. Further, we investigated the role of the cluster of differentiation CD138, Ki67, CD56, and CD117 immunoexpression in the differential diagnosis of PCG from plasma cell dyscrasias. All histopathologically confirmed cases of PCG, whose relevant details could be obtained, were included in this study. They were subjected to panel of immunohistochemical markers to exclude plasma cell malignancies. Further, published English literature for PCG since 1970-2020 was reviewed. Nine histopathologically confirmed cases of PCG, were retrieved from the archives of our department. The cases comprised 3 males and 6 females with their ages ranging between 14 and 82 years. The plasma cells exhibited equivocal reactivity for kappa and lambda; and immunonegativity for CD56, CD117 with low Ki67 proliferation index. Published literature in English showed 43 cases of PCG were predominantly female; the diffuse involvement of maxilla and mandible was a common finding. In addition to kappa lambda reactivity, an immunoprofile of CD138, Ki67, CD56, and CD117 may be used as a diagnostic adjunct to exclude malignant plasma cell lesions in confusing cases.

Correlation of Somatostatin Receptor 1-5 Expression, [68Ga]Ga-DOTANOC, [18F]F-FDG PET/CT and Clinical Outcome in a Prospective Cohort of Pancreatic Neuroendocrine Neoplasms.

Simple SummaryThe need for prognostic and predictive biomarkers in pancreatic neuroendocrine neoplasms (PNENs) is great. Overexpression of somatostatin receptors (SSTRs) provides a molecular basis for imaging these tumors with 68Ga-labeled somatostatin (SST) PET/CT and for treatment with somatostatin analogs. We evaluated all 5 somatostatin receptors (SSTR1-5) with immunohistochemistry and prospectively compared the results with both [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT in a cohort of 21 non-functional (NF) PNENs. SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. High SSTR5 expression correlated with a low Ki-67 proliferation index, suggesting a better prognosis for these patients. Thus, our results confirm that SSTR2 has the highest impact on SSTR PET signaling of PNENs.Purpose: The aim of this study was to correlate immunohistochemical (IHC) tissue levels of SSTR1-5 with the receptor density generated from [68Ga]Ga-DOTANOC uptake in a prospective series of NF-PNENs. Methods: Twenty-one patients with a total of thirty-five NF-PNEN-lesions and twenty-one histologically confirmed lymph node metastases (LN+) were included in this prospective study. Twenty patients were operated on, and one underwent endoscopic ultrasonography and core-needle biopsy. PET/CT with both [68Ga]Ga-DOTANOC and [18F]F-FDG was performed on all patients. All histological samples were re-classified and IHC-stained with monoclonal SSTR1-5 antibodies and Ki-67 and correlated with [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT. Results: Expression of SSTR1-5 was detected in 74%, 91%, 80%, 14%, and 77% of NF-PNENs. There was a concordance of SSTR2 IHC with positive/negative [68Ga]Ga-DOTANOC finding (Spearman’s rho 0.382, p = 0.043). All [68Ga]Ga-DOTANOC-avid tumors expressed SSTR2 or SSTR3 or SSTR5. Expression of SSTR5 was higher in tumors with a low Ki-67 proliferation index (PI) (−0.353, 95% CI −0.654–0.039, p = 0.038). The mean Ki-67 PI for SSTR5 positive tumors was 2.44 (SD 2.56, CI 1.0–3.0) and 6.38 (SD 7.25, CI 2.25–8.75) for negative tumors. Conclusion: SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. Our prospective study confirms SSTR2 to be of the highest impact for SST PET/CT signal.

S3149 Plexiform Fibromyxoma: A Perplexing Condition of the Stomach

Introduction: Plexiform fibromyxoma (PF) is a rare, often benign tumor of mesenchymal origin typically found within the stomach. It features a plexiform cellular architecture of myofibroblasts encircled by a myxoid intercellular matrix with rich vasculature. Takahashi et. al described the first cases of known PF in 2007. It was officially recognized as a subtype of gastric mesenchymal neoplasm by the World Health Organization in 2010. Here, we present a case of PF detected during surveillance endoscopy. Case Description/Methods: 64-year-old male presented for esophagogastroduodenoscopy (EGD) with ablation of Barrett esophagus with low-grade dysplasia. He had undergone 4 previous EGDs remarkable for hyperplastic antral polyps which were removed. His most recent physical exam and labs were unremarkable. During the EGD, he was found to have antral erythema with no clear discernable lesions (figure 1). Biopsies of the region were obtained which stained negative for cytokeratin AE1/AE3, S100, CKIT/CD34 (in lesional cells), and DOG1 while positive for smooth muscle actin (SMA), consistent with PF. Discussion: The clinical presentation of PF is usually nonspecific. Commonly reported symptoms include abdominal pain, fullness, nausea, and vomiting, followed by complications of symptomatic anemia such as syncope. Reported size of PF lesions range from 0.8 - 17.0 cm. Immunohistochemically, the tumor cells are positive for SMA and vimentin, and can show focal or partial staining for CD10, desmin and caldesmon. The spindle cells are negative for DOG-1, C-KIT, epithelial membrane antigen (EMA), ALK, S-100 and CD34 with a low Ki-67 proliferation index. On CT or MRI imaging, PF appears as a solid, cystic, or solid/cystic mass with well-defined borders. Due to the increased vascularity of the tumor, CT with contrast may show mild enhancement of the solid portion during the arterial phase and strengthened progressive enhancement during the venous and delayed phases. Differential diagnoses for these tumors include gastrointestinal stromal tumors (GIST), leiomyoma, granular cell tumor, schwannoma, myxoma and angiomyxoma, gastric blastoma and malignant epithelioid tumor with GLI1 rearrangement. The current treatment of choice is surgical excision. Given the lack of clear lesion in our patient, further imaging will be obtained to attempt to determine margins. Increased awareness by endoscopists and pathologists of this condition is necessary for accurate diagnosis and management of this condition.Figure 1.: Endoscopic visualization of pre-pyloric ulcers.