Mitotic Rate Research Articles

Carcinoid tumors outside the abdomen.

Neuroendocrine tumors (NETs) are epithelial malignancies that can arise from multiple tissues. Gastrointestinal (GI) NETs are the most common; in this review of extra-abdominal carcinoid tumors, we focus our discussion on bronchial and thymic carcinoid tumors. Bronchial carcinoid tumors comprise a quarter of all NETs and less than 2% of all lung cancers. Thymic carcinoid tumors are extremely rare, accounting for 5% of thymic tumors. Both bronchial and thymic carcinoid tumors are histologically classified as either typical or atypical based on their mitotic rate (less than 2 or 2-10 mitoses per 10 high-powered fields (HPF), respectively). Both bronchial and thymic carcinoids can present with symptoms of obstruction and potentially carcinoid syndrome. The gold standard of management of bronchial and thymic carcinoid tumors is surgical resection. For patients with advanced disease, first-line systemic therapy is generally somatostatin analog monotherapy with octreotide or lanreotide. In patients with refractory disease, therapy generally involves peptide receptor radioligand therapy, everolimus, or cytotoxic chemotherapy. There are ongoing, prospective trials comparing the mainstays of systemic therapy for these patients, as well as ongoing evaluations of immune checkpoint inhibitors and multi-kinase inhibitors. Prognosis for both bronchial and thymic carcinoid tumors depends on histologic grade, local versus invasive disease, and extent of metastases. Herein we provide a summary of the pathophysiologic and clinical background, the current state of the field in diagnosis and management, and note of key ongoing prospective trials for patients with bronchial and thymic carcinoid tumors.

Fetal Brain Tumors, a Challenge in Prenatal Diagnosis, Counselling, and Therapy

Fetal brain tumors are a rare entity with an overall guarded prognosis. About 10% of congenital brain tumors are diagnosed during fetal life. They differ from the postnatally encountered pediatric brain tumors with respect to location and tumor type. Fetal brain tumors can be benign or malignant and infiltrate or displace adjacent brain structures. Due to their high mitotic rate, they can show rapid growth. Outcome depends on age of diagnosis, size, and histological tumor type. Findings like polyhydramnios and macrocephaly encountered on routine ultrasound are frequently associated. Detailed prenatal anomaly scan and subsequent fetal magnetic resonance imaging (MRI) may identify the brain tumor and its severity. Both maternal and fetal prognosis should be included in prenatal counselling and decision making.

Hamster polyomavirus-associated T-cell lymphomas in Syrian hamsters (Mesocricetus auratus).

Hamster polyomavirus (HaPyV) infection has been associated with lymphomas in Syrian hamsters. In the present study, 14 cases of lymphoma in pet Syrian hamsters were pathologically examined and the involvement of HaPyV was investigated. Among 14 cases, 11 were abdominal and 3 were cutaneous lymphomas. The average ages of hamsters with abdominal lymphoma and cutaneous lymphoma were 7 months (range: 4-12 months) and 14 months (range: 6-23 months), respectively. Histologically, abdominal lymphomas were characterized by the diffuse growth of tumor cells with intermediate or large nuclei, low mitotic rates, the presence of tingible body macrophages, and the T-cell immunophenotype. Furthermore, 4/11 abdominal lymphomas were immunopositive for T-cell intracellular antigen-1, suggesting cytotoxic T-cell lymphomas. Cutaneous lymphomas were diagnosed as nonepitheliotropic T-cell lymphoma. Polymerase chain reaction (PCR) detected HaPyV DNA in 12/14 samples, and a sequence analysis of PCR amplicons confirmed >99% nucleotide identity to the published HaPyV sequences. In situ hybridization (ISH) for HaPyV DNA resulted in diffuse nuclear signals within tumor cells in 10/14 cases. Consistent with previous findings, all HaPyV-associated lymphomas were observed in the abdominal cavity of young hamsters. Polymerase chain reaction and ISH were useful for identifying the involvement of HaPyV in lymphomas, and ISH results indicated the presence of episomal HaPyV in neoplastic lymphocytes. The present study suggests that HaPyV infection is highly involved in abdominal lymphomas in young pet Syrian hamsters in Japan and provides diagnostic information on HaPyV-associated lymphoma.

Impact of the COVID-19 Pandemic on Melanoma Diagnosis: Increased Breslow Thickness in Primary Melanomas—A Single Center Experience

Early melanoma diagnosis plays a key role in ensuring best prognosis with good survival rates. The ongoing global COVID-19 pandemic has greatly impacted global and national healthcare systems, thus making it a real challenge. The aim of this study was to evaluate the impact of the pandemic on diagnostic delay in melanoma patients in Serbia. In this retrospective study, we included patients treated at the university hospital in Serbia's capitol over a period of five years and three months. We compared the prepandemic (01/JAN/17-14/MAR/20) and pandemic periods (15/MAR/20-31/MAR/22) by evaluating patient demographic data, melanoma subtype, Breslow thickness, Clark level, ulceration status, mitotic index rate and pT staging. We observed a significant reduction in the number of diagnosed patients (86.3 vs. 13.7%; p = 0.036), with melanomas having an increased median Breslow thickness (1.80 vs. 3.00; p = 0.010), a higher percentage of Clark IV-V level lesions (44.0% vs. 63.0%; p = 0.009), an increase in median mitotic index rate (2 vs. 5; p < 0.001) and a trend of increase in lesions thicker than 2 mm (37.8% vs. 53.7%; p = 0.026). We believe that this study can be a useful scenario guide for future similar events, highlighting the importance of preventive measures and timely diagnosis for the best patient outcomes.

Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques.

Administration of a novel and selective small molecule integrin αvβ6 inhibitor, MORF-627, to young cynomolgus monkeys for 28 days resulted in the rapid induction of epithelial proliferative changes in the urinary bladder of 2 animals, in the absence of test agent genotoxicity. Microscopic findings included suburothelial infiltration by irregular nests and/or trabeculae of epithelial cells, variable cytologic atypia, and high mitotic rate, without invasion into the tunica muscularis. Morphologic features and patterns of tumor growth were consistent with a diagnosis of early-stage invasive urothelial carcinoma. Ki67 immunohistochemistry demonstrated diffusely increased epithelial proliferation in the urinary bladder of several monkeys, including those with tumors, and αvβ6 was expressed in some epithelial tissues, including urinary bladder, in monkeys and humans. Spontaneous urothelial carcinomas are extremely unusual in young healthy monkeys, suggesting a direct link of the finding to the test agent. Inhibition of integrin αvβ6 is intended to locally and selectively block transforming growth factor beta (TGF-β) signaling, which is implicated in epithelial proliferative disorders. Subsequent in vitro studies using a panel of integrin αvβ6 inhibitors in human bladder epithelial cells replicated the increased urothelial proliferation observed in monkeys and was reversed through exogenous application of TGF-β. Moreover, analysis of in vivo models of liver and lung fibrosis revealed evidence of epithelial hyperplasia and cell cycle dysregulation in mice treated with integrin αvβ6 or TGF-β receptor I inhibitors. The cumulative evidence suggests a direct link between integrin αvβ6 inhibition and decreased TGF-β signaling in the local bladder environment, with implications for epithelial proliferation and carcinogenesis.

Melanoma of the Scalp and Neck: A Population-Based Analysis of Survival and Treatment Patterns.

Melanoma is an aggressive skin cancer. Large demographic and clinic-pathologic studies are required to identify variations of tumour behavior. The aim of our study was to offer updated epidemiologic data on the scalp and neck melanoma with an overall survival analysis. The SEER database was searched for all scalp and neck melanoma in adult patients between 2000 and 2019. Demographic and clinic-pathologic variables were described. Their impact on overall survival was assessed with the log-rank test after Kaplan-Meier model. A multivariable cox-regression was conducted to identify predictors of decreased survival. A p-value of &lt;0.005 was considered statistically significant. 20,728 Melanomas of the scalp and neck were identified. Mean age was 62.5 years. Gender ratio was 76.3% males. 79% of the tumours were localized at diagnosis. Increasing age, male gender, tumour ulceration, high mitotic rate or nodular subtype were independent prognostic factors of decreased overall survival. Surgery with less than 1 cm margin is associated with the best overall survival in this cohort. No significant difference in OS was seen between less than 1 cm and 1 to 2 cm margins. Knowledge of negative prognostic factors might help identify subgroups at risk and adapt their oncologic treatment.

Unmeasured factors are associated with the use of completion lymph node dissection (CLND) in melanoma.

Completion lymph node dissection (CLND) was the standard treatment for patients with melanoma with positive sentinel lymph nodes (SLN) until 2017when data from the DeCOG-SLT and MLST-2 randomized trials challenged the survival benefit of this procedure. We assessed the contribution of patient, tumor and facility factors on the use of CLND in patients with surgically resected Stage III melanoma. Using the National Cancer Database, patients who underwent surgical excision and were found to have a positive SLN from 2012 to 2017 were included. A multivariable mixed-effects logistic regression model with a random intercept for the facility was used to determine the effect of patient, tumor, and facility variables on the risk of CLND. Reference effect measures (REMs) were used to compare the contribution of contextual effects (unknown facility variables) versus measured variables on the variation in CLND use. From 2012 to 2017, the overall use of CLND decreased from 59.9% to 26.5% (p < 0.0001). Overall, older patients and patients with government-based insurance were less likely to undergo CLND. Tumor factors associated with a decreased rate of CLND included primary tumor location on the lower limb, decreasing depth, and mitotic rate <1. However, the contribution of contextual effects to the variation in CLND use exceeded that of the measured facility, tumor, time, and patient variables. There was a decrease in CLND use during the study period. However, there is still high variability in CLND use, mainly driven by unmeasured contextual effects.

Increased replication origin firing links replication stress to whole chromosomal instability in human cancer

Chromosomal instability (CIN) is a hallmark of cancer and comprises structural CIN (S-CIN) and numerical or whole chromosomal CIN (W-CIN). Recent work indicated that replication stress (RS), known to contribute to S-CIN, also affects mitotic chromosome segregation, possibly explaining the common co-existence of S-CIN and W-CIN in human cancer. Here, we show that RS-induced increased origin firing is sufficient to trigger W-CIN in human cancer cells. We discovered that overexpression of origin firing genes, including GINS1 and CDC45, correlates with W-CIN in human cancer specimens and causes W-CIN in otherwise chromosomally stable human cells. Furthermore, modulation of the ATR-CDK1-RIF1 axis increases the number of firing origins and leads to W-CIN. Importantly, chromosome missegregation upon additional origin firing is mediated by increased mitotic microtubule growth rates, a mitotic defect prevalent in chromosomally unstable cancer cells. Thus, our study identifies increased replication origin firing as a cancer-relevant trigger for chromosomal instability.

Sex differences in patients with gastrointestinal stromal tumours: do they exist and does it affect survival?

Sex differences in cancer have gained attention in recent years. The role of sex as a prognostic factor in gastrointestinal stromal tumours (GIST) has not been well established. The aim of this research was to elucidate potential sex differences in GIST patients and the influence of sex on disease-specific survival (DSS). A review of the literature was carried out to obtain an overview of all literature with sex as a covariate on GIST survival analyses. Furthermore, in the Dutch GIST Registry, GIST characteristics between males and females were compared and the influence of sex on DSS was analysed. A total of 118 articles from the review of the literature met our selection criteria; 58% of the articles found no sex difference in survival and 42% did find a sex difference. All differences favoured female patients, although there was substantial overlap of individual patients in the various reported groups. The Dutch GIST Registry cohort consisted of 1425 patients (46% female). Compared with female patients, male patients had larger tumours (mean 9.0 cm versus 7.9 cm) and higher mitotic rates (34.4% versus 28.0% >5 mitoses/5 mm2). GIST in males was more often metastasized at diagnosis (21.3% versus 13.7%) and incurable (38.5% versus 31.0%). Male patients less often received surgery of the primary tumour (71.7% versus 78.9%), but did experience more tumour ruptures (18.2% versus 13.3%). Male patients had a worse DSS than females. This was not statistically significant when corrected for differences in GIST characteristics. In case of sex differences in GIST in the literature, male patients have a worse outcome. In our Dutch GIST cohort a similar finding was made, but sex was shown not to be an independent factor. Male patients more often had aggressive GISTs, with larger tumours, higher mitotic rates, more tumour ruptures, and metastases, which could explain the sex differences in DSS.

Extranodal Follicular Dendritic Cell Sarcoma of the Head and Neck Region: A Clinicopathological Study of 7 Cases.

Background. Follicular dendritic cell (FDC) sarcoma is a rare neoplasm arising from follicular dendritic cells (FDCs). It can be nodal or extranodal. Histological diagnosis of extranodal FDC sarcoma in the head and neck region is challenging and a significant percentage are misdiagnosed. Objectives. To report clinicopathological features of head and neck extranodal FDC sarcoma cases and discuss differential diagnoses. Methods. Seven head and neck extranodal FDC sarcomas were retrieved and clinicopathological features were noted. Results. Two tumors each involved parapharyngeal space and tonsil while remaining cases involved the parotid, soft tissue of neck and oropharynx. Age range was 12 to 79 years (mean and median age were 40 and 44 years respectively) and there was a male predilection (6 males: 1 female). All showed spindle to ovoid cells arranged in fascicles, whorls and/or storiform pattern. Mitoses ranged from 3 to 20/mm2. All tumors expressed CD21 and CD23. Two patients died of their disease at 9 and 16 months. Both had tumors larger than 5 cm with ≥10 mitoses/mm2. Three patients were alive at 12, 44 and 184 months. Conclusions. There was a distinct male predominance in our cohort. FDC sarcoma should be included in the differential diagnosis of spindle cell extranodal neoplasms in the head and neck with a whorled growth pattern and intratumoral lymphocytes. Head and neck region tumors show similar clinicopathologic characteristics as their counterparts at other locations with potential for aggressive behavior especially in tumors greater than 5 cm in size and with high mitotic rates.

Effects of BRAF V600E and NRAS mutational status on the progression-free survival and clinicopathological characteristics of patients with melanoma.

Hotspot mutations of the BRAF and NRAS genes are the most common genetic alterations in invasive cutaneous melanoma; however, the prognostic significance of BRAF and NRAS co-mutations remains controversial. The present study aimed to determine the association between NRAS and BRAF mutation status and the clinicopathological characteristics of patients with stage IA-IIC melanoma. A total of 118 patients who underwent surgical treatment for stage IA-IIC melanoma at the Riga East University Hospital between 2012 and 2018 were retrospectively enrolled in the present study. BRAF and NRAS mutation status was assessed by digital droplet PCR using the BRAFV600, NRAS Q61 and NRAS G12/G13 Screening Assays. The association between mutation status and clinicopathological features and progression-free survival (PFS) was then analyzed. The BRAF V600 mutation was detected in 67 out of 118 patients (56.8%). The PFS did not differ between patients with BRAF wild-type and BRAF-mutant melanoma. NRAS mutations were detected in 35 out of 118 patients (29.6%). The NRAS mutational status was associated with Breslow thickness (P=0.035), tumor type (P=0.020; χ2=0.20), mitotic rate (P=0.025) and lymphovascular invasion (P=0.02; χ2=0.20). Patients with NRAS-mutant melanoma had significantly worse PFS compared with NRAS wild-type melanoma (HR=12.30; 95% CI=5.78-26.21, P<0.0001). Furthermore, BRAF and NRAS co-mutant melanoma was associated with a significantly worse PFS compared with BRAF-mutant melanoma (HR=6.30; 95% CI=3.10-12.70, P<0.0001). In conclusion, NRAS-mutant and NRAS/BRAF co-mutant stage IA-IIC melanoma was associated with worse PFS compared with NRAS wild-type and BRAF-mutant melanoma. The assessment of NRAS mutation status in melanoma in routine clinical practice may be beneficial for the risk stratification of disease progression for primary non-metastatic malignant melanoma.

An NTRK-1-associated soft tissue tumor showing distinctive nodules with peripheral accentuation of cellularity.

Lipofibromatosis-like neural tumor is a recently described entity defined by a low-cellularity spindle cell infiltrate in the subcutaneous fat with admixed inflammatory cells. This tumor is histopathologically similar to lipofibromatosis, but unlike lipofibromatosis shows reactivity for S100 and has an NTRK-1 kinase fusion. These lesions are locally aggressive but appear to have a negligible metastatic potential. Subsequently, a more cellular variant has been described with generally low mitotic rate. This variant also displays S100 reactivity and kinase fusions (typically involving NTRK-1), but it has a low risk of metastasis. In this report, we describe a case that aligns with the more cellular variant of NTRK-1 kinase fusion tumors on histopathologic, immunohistochemical, and molecular grounds, but in addition has distinctive nodules with peripheral accentuation of cellularity, reminiscent of those present in epithelioid malignant peripheral nerve sheath tumors. This latter feature is previously undescribed in NTRK kinase fusion soft tissue tumors and offers further support for the presumed neural differentiation of this neoplasm.

“Growing fibroadenoma”: Are there clinical and pathological features predicting a phyllodes tumor on surgical excision?

In cases of growth of FA on imaging, core needle biopsies (CNB) are often performed to rule out phyllodes tumor (PT). We aim to focus on “growing FAs” and to identify clinical and histopathologic features that are likely to predict a PT on excision. Thirty-four FAs with radiologic documentation of growth were included. Various clinical and pathological features such as age, body mass index (BMI), lesion size, and growth rate were recorded. On excision, 17 cases (50 %) were FAs, whereas 16 (47 %) were re-classified as benign PT despite only 19 % being suspicious for PT on CNB. PT patients were older (mean age 42.6) than those with FAs (mean age 28.2), p = 0.0002. All false negative cases demonstrated intracanalicular growth. Mitotic rate was the most significant histologic feature in PT on excision compared to others, such as lesion circumscription and stromal cellularity. Recognition and careful counting of mitotic rate, especially with intracanalicular patterns in growing FAs, can potentially prevent missing a PT on CNB. In patients with “growing FAs” who are ≥40 years of age, excision may be recommended due to the high likelihood of PT diagnosis on excision and high false negative rate on CNB.

The Integrated 31-Gene Expression Profile Test (i31-GEP) for Cutaneous Melanoma Outperforms the CP-GEP at Identifying Patients who can Forego Sentinel Lymph Node Biopsy when Applying NCCN Guidelines

Introduction: Eighty-eight percent of patients who receive a sentinel lymph node biopsy (SLNB) receive a negative result. Current guidelines suggest avoiding SLNB if the risk of positivity is &lt;5%. A low threshold for performing SLNB indicates worry about missing positive nodes but results in many unnecessary biopsies. The integrated 31-gene expression profile (i31-GEP) test combines the 31-GEP with Breslow thickness, age, ulceration, and mitotic rate using a validated neural network algorithm to identify patients with &lt;5% risk by reporting a precise, individualized likelihood score. Using logistic regression, a separate GEP (8 genes plus Breslow thickness and age; CP-GEP) also aims to identify patients who can forego SLNB by binning patients into low- and high-risk categories. This study compared the i31-GEP for SLNB with the CP-GEP to identify patients who can safely forego SLNB. Methods: This study evaluated the genes, gene pathways, and relative contribution of the two gene signatures relative to clinical and pathologic factors and further analyzed patients with T1b-T2 tumors from previously published studies in U.S. cohorts for the i31-GEP (n=763) and CP-GEP (n=153). A ratio of true-to-false-negative i31-GEP for SLNB and CP-GEP test results was compared to the guideline-established ratio of 19 negatives to one missed positive (19:1) if foregoing SLNB using a 5% risk threshold. Results: The i31-GEP had a 30:1 true-to-false-negative ratio, compared to 15:1 using CP-GEP. In T1b tumors, the i31-GEP ratio increased to 35:1 compared to 14:1 using CP-GEP. Limitations: Retrospective design, which could lead to bias. Patients included in both analyses were primarily from institutional surgical centers, and referral bias may not make the result generalizable. Conclusion: Only the i31-GEP provided benefit over guideline-established care for identifying patients with low risk of SLN positivity.

Impact of the COVID-19 Pandemic on Melanoma Diagnosis in Romania-Data from Two University Centers.

The COVID-19 pandemic affected the healthcare system in our country and led non-COVID patients to postpone medical visits that were not urgent. The purpose of this study was to investigate the impact of the first year of the COVID-19 pandemic on the trends in melanoma diagnosis and to compare the pathological characteristics of melanoma patients before and during the pandemic. The number of primary cutaneous melanomas diagnosed each month between 1 March 2019 and 29 February 2020 (pre-COVID-19) and between 1 March 2020 and 28 February 2021 (COVID-19) in the North-Western Region of Romania (Cluj and Bihor counties) was determined. The pathological characteristics of melanomas diagnosed in the two intervals were compared. The number of melanoma diagnoses substantially decreased during the pandemic, with 66 (-19.3%) fewer cutaneous melanomas being diagnosed in the first year of the pandemic when compared with the previous year. The tumor thickness and mitotic rate were significantly higher in cases found during the COVID-19 pandemic. Our study suggests that COVID-19 has delayed diagnosis in patients with melanoma, leading to the detection of thicker melanomas that may increase morbidity and mortality. Further studies are needed to determine the consequences of this delay on outcomes.

Prognostic Nomogram for Gastrointestinal Stromal Tumors after Surgery Based on the SEER Database.

We aimed to determine prognostic factors and develop an effective and practical nomogram for predicting cancer-specific survival in gastrointestinal stromal tumor (GIST) patients. Postoperative data were obtained from the SEER database (2000-2018). Patients were divided into training and validation cohorts at random (7 : 3). Prognostic factors were screened, and a prognostic nomogram was established using log-rank testing and Cox regression. We used DCA, ROC curves, C-index, and calibration curves to evaluate our model's predictive performance. The clinical value of the nomogram and the modified National Institute of Health (M-NIH) classification were compared using the NRI and IDI. The Kaplan-Meier method was applied to examine survival by risk group, and log-rank tests were applied to compare variations in survival curves. Independent prognostic risk factors associated with cancer-specific survival on multivariate Cox proportional hazards regression analysis were age, race, and tumor location, size, grade, and stage. Clinically relevant variables need to be considered in addition to statistically significant variables when developing prognostic models to aid clinical decision-making. We included two additional variables (mitotic rate and chemotherapy) when constructing the prognostic model. The C-index was 0.766 (95% confidence interval (CI): 0.737-0.794) in the training cohort and 0.795 (95% CI: 0.754-0.836) in the internal validation group suggesting robustness. The areas under the ROC curve for three-year and five-year survival were >0.700, indicating satisfactory discrimination. The calibration curves showed good agreement between the predictions of the nomogram and the actual results. The NRI (0.346 for 3-year and 0.265 for 5-year cancer-specific survival for patients with GIST (GSS) prediction; validation cohort: 0.356 for 3-year and 0.246 for 5-year GSS prediction) and IDI values (0.047 for 3-year and 0.060 for 5-year GSS prediction; validation cohort: 0.071 for 3-year and 0.084 for 5-year GSS prediction) suggested that the established nomogram performed significantly better than the M-NIH classification. The DCA indicated that the nomogram was clinically useful and had a high discriminative ability in identifying patients who were at high risk of poor outcomes. According to nomogram findings, patients were divided into three groups (high, moderate, and low risk), with significantly different prognoses in both cohorts. Our nomogram satisfactorily predicted survival in postsurgical GIST patients, which may assist clinicians to evaluate the postoperative status and guide subsequent treatments.

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.

Giant Cell Tumor of Soft Tissue Arising from Breast with Distant Metastases Post-therapy: A Rare Entity

Abstract Introduction/Objective Giant-cell tumor of soft tissue (GCT-ST) is rare and indistinguishable from giant cell tumor of bone. GCT-ST arising in the soft tissue of breast is exceedingly rare, with only ten cases previously reported. Methods/Case Report We present a 46-year-old female with history of lupus, presenting with an enlarging mass in her left breast. Needle core biopsy showed a hypercellular proliferation of spindle cells arranged in fascicles and sheets with infiltrative borders. A primary diagnosis of high-grade spindle cell lesion was rendered. The patient’s clinical workup was negative for lesions elsewhere. The patient subsequently underwent a left segmental mastectomy. Histopathology revealed a tumor composed predominantly of high-grade spindled and epithelioid cells with tumor necrosis, a high mitotic rate, and several scattered multinucleated giant cells. Immunohistochemical stains showed positivity for CD68 and CD34 in giant cells only, while the tumor cells were positive for Vimentin and CD99. Pancytokeratin, cytokeratin 5/6, HMB-45, smooth muscle actin, myogenin, myo-D1, and desmin were all negative. Based on the morphology and immunohistochemistry, the tumor was diagnosed as a malignant GCT-ST. Adjuvantly, she underwent chemoradiation; however, within four months, she developed new nodules in the lung, left ventricle, and liver, radiologically consistent with metastases. Results (if a Case Study enter NA) NA Conclusion Although GCT-ST possesses a low malignant potential, its unpredictable behavior poses a challenge. Metastases may develop even after excision with adequate surgical margins. To our knowledge, this is the first case of primary malignant GCT-ST of the breast with distant metastases post-therapy. This entity, with its clinical complexities, remains a diagnostic and therapeutic challenge.

ODP025 Adrenocortical Carcinoma: A Rare but Life-Threatening Malignancy

Abstract Introduction Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal glands, but often presents an aggressive behavior with variable prognosis. Median age of diagnosis is in the fifth to sixth decade of life with a median survival rate of 3-4 years. Complete surgical resection is the first line and only curative therapy. In patients with high-risk ACC, adjuvant therapy with mitotane, alone or in combination with other cytotoxic agents, may be used. Case description Case of a 33-year-old female with history of thyroid nodules presenting with a one year history of amenorrhea and hirsutism. One year prior to evaluation, the patient developed an intense right flank pain requiring abdominal-pelvic CT. It showed a solid heterogeneous right flank mass measuring 16×16×12 cm, 44Hounsfield units without enhanced contrast washout. Hormonal workup at that time resulted with DHEA-S &amp;gt; 10,000ng/mL(nl 350-4300), androstenedione 10.7 ng/mL (nl 0.35–2.78), total testosterone 3.21 ng/mL (nl &amp;lt; 0.52), midnight salivary cortisol at 14 nmol/L (nl &amp;lt; 3.6) and normal FSH, ACTH and serum morning cortisol. Staging chest CT exhibited bilateral pulmonary embolisms. Patient underwent right open total adrenalectomy of a necrotic/hemorrhagic mass measuring 20×16×9 cm with complete resection. Histology consistent with a low-grade ACC with a mitotic rate 18/50 HPF, with capsular invasion but no lymphovascular invasion and clear margins. It was stratified as stage T2N0M0. Immunohistochemistry's were positive for Melan-A, calretinin, synaptophysin, and inhibin. Ki67 was 80%. She was started on hydrocortisone replacement. PET/CT scan showed hypermetabolic focus at the right thyroid lobe (previously biopsied with benign findings), but otherwise no pathologic 18 FDG uptake related to known oncologic disease. Due to her high risk of recurrence, the patient was started on mitotane 2 g daily as adjuvant therapy but had to discontinue therapy after 1 month due to lack of availability. One year after initial presentation, she was evaluated at our clinics and after discussion with Oncology Service restarting mitotane was recommended. However, marked transaminitis was noted along with right abdominal discomfort. Abdominal MRI revealed hepatic hypo-enhancing masses suggestive of liver metastases, with the largest measuring 6.7cm. Patient underwent right partial hepatectomy and was found with extensive metastatic carcinoma and lymph node involvement. Therapy with mitotane was restarted, pending chemotherapy initiation. Conclusion The goal of any therapy for ACC is to alleviate symptoms and prolong survival. Mitotane, an adrenolytic drug used as palliative treatment, is among therapeutic options. Due to the rarity of the disease, data regarding its use is mixed due to limited randomized controlled trials. Nevertheless, it supports improvement in recurrence-free and possibly overall-survival after complete radical resection in stage I, II or III ACC. Unfortunately, there is still marked individual variation in outcomes. Presentation: No date and time listed

Clinical Utility of Dermoscopy and 31-Gene Expression Profiling by Dermatology Providers in Melanoma Management Care.

A 31-gene expression profile (31-GEP) test that predicts metastatic risk in patients with cutaneous malignant melanoma (CMM) has previously been validated and is available for clinical use. The test dichotomizes patients into lower risk and higher risk groups based on differences that correspond to unique genetic expression patterns. Although the impact of such a test on dermatology providers' clinical decision-making has been studied, little is known about whether there exists an association between certain clinical features, such as dermoscopy, and 31-GEP results. In this retrospective analysis of 31-GEP test results ordered by dermatologists, we evaluated the frequency of dermoscopic features, using a modified dermoscopy three-point checklist, in 17 cases (n=17) and compared these findings to other key clinicopathologic features including tumor thickness, ulceration, and mitotic rate to 31-GEP results. Additionally, we evaluated the dermatologist's perspective and incorporation of GEP testing as part of patient discussion on melanoma management. 31-GEP stratified patients into 4 groups; groups 1A and 1B are considered low risk of metastasis or recurrence, while 2A and 2B are considered high risk. Of the 17 cases, we had fifteen group 1A (88.23%), one 1B (5.88%), and one 2B (5.88%) result. Overall frequency of dermoscopic features is as follows; 100% of lesions presented with asymmetry, 47% with round structures, and 70.6% with blue-white color. The average time providers spent explaining and ordering the test was 15 minutes, with a range of 10 to 20 minutes. This study represents our experience and understanding of the dermatologist&rsquo;s role ordering 31-GEP in the care pathway of melanoma patients and we recommend that dermatology providers consider ordering the test for newly diagnosed CMM patients. J Drugs Dermatol. 2022;21(12): doi:10.36849/JDD.6889.