WCRC-25: A novel luminal Invasive Lobular Carcinoma cell line model.

Breast cancer is categorized by the molecular and histologic presentation of the tumor, with the major histologic subtypes being No Special Type (NST) and Invasive Lobular Carcinoma (ILC). ILC are characterized by growth in a single file discohesive manner with stromal infiltration attributed to their hallmark pathognomonic loss of E-cadherin ( CDH1 ). Few ILC cell line models are available to researchers. Here we report the successful establishment and characterization of a novel ILC cell line, WCRC-25, from a metastatic pleural effusion from a postmenopausal Caucasian woman with metastatic ILC. WCRC-25 is an ER-negative luminal epithelial ILC cell line with both luminal and Her2-like features. It exhibits anchorage independent growth and haptotactic migration towards Collagen I. Sequencing revealed a CDH1 Q706* truncating mutation, together with mutations in FOXA1, CTCF, BRCA2 and TP53 , which were also seen in a series of metastatic lesions from the patient. Copy number analyses revealed amplification and deletion of genes frequently altered in ILC while optical genome mapping revealed novel structural rearrangements. RNA-seq analysis comparing the primary tumor, metastases and the cell line revealed signatures for cell cycle progression and receptor tyrosine kinase signaling. To assess targetability, we treated WCRC-25 with AZD5363 and Alpelisib confirming WCRC-25 as susceptible to PI3K/AKT signaling inhibition as predicted by our RNA sequencing analysis. In conclusion, we report WCRC-25 as a novel ILC cell line with promise as a valuable research tool to advance our understanding of ILC and its therapeutic vulnerabilities. Financial support: The work was in part supported by a Susan G Komen Leadership Grant to SO (SAC160073) and NCI R01 CA252378 (SO/AVL). AVL and SO are Komen Scholars, Hillman Foundation Fellows and supported by BCRF. This project used the UPMC Hillman Cancer Center and Tissue and Research Pathology/Pitt Biospecimen Core shared resource which is supported in part by award P30CA047904. This research was also supported in part by the University of Pittsburgh Center for Research Computing, RRID:SCR_022735, through the resources provided. Specifically, this work used the HTC cluster, which is supported by NIH award number S10OD028483. Finally, partial support was provided by the Magee-Womens Research Institute and Foundation, The Shear Family Foundation, and The Metastatic Breast Cancer Network.

Synchronous Bilateral Breast Cancer: A Case Report Piloting and Evaluating the Implementation of the AI-Powered Large Language Model (LLM) ChatGPT.

Primary breast carcinoma is the most common cancer type in women, and although bilateral synchronous breast cancers (s-BBC) remain quite rare, the reported incidence may increase with the adoption of more sensitive imaging modalities. Here, we present a case of histomorphological and clinically distinct s-BBC, together with a discussion of clinical management decisions, prognosis, and treatment standards and how these relate to outcomes vis-à-vis more established standards in unifocal breast carcinoma. The case report also constitutes a pilot and formal evaluation of a large language model (LLM) of ChatGPT as a tool to aid in generating a single patient case report.

Unusual Tissue - Unusual Issue: Pancreatic Heterotopia Presenting as Gastric Outlet Obstruction.

Pancreatic heterotopia (PH) is a common, but typically small (<1 cm), incidental and asymptomatic finding; however, PH should be considered even for large and symptomatic upper gastrointestinal masses. A 27-year-old white woman presented with a 3-week history of burning epigastric pain, nausea, early satiety, and constipation. Physical examination revealed epigastric and right upper quadrant tenderness with normal laboratory workup, but imaging revealed a 5-cm, partly cystic mass arising from the gastric antrum with resulting pyloric stenosis and partial gastric outlet obstruction. Endoscopic ultrasound-guided fine needle aspiration revealed PH - an anomalous pancreatic tissue lying in a nonphysiological site. The patient ultimately underwent a resection and recovered uneventfully, with a complete pathologic examination revealing normal exocrine pancreatic tissue (PH type 2) without malignant transformation. We report a case of heterotopic pancreas manifesting as severe gastric outlet obstruction, in addition to a thorough diagnostic workup and surgical follow-up, in a young adult. Differential diagnoses and features that speak to benignity of a large, symptomatic mass lesion (PH in particular) are discussed.

Acquisition of Cabozantinib-Sensitive MET D1228N Mutation During Progression on Crizotinib in MET-Amplified Triple-Negative Breast Cancer.

BACKGROUND: Targeting of somatic MET mutations using crizotinib has led to strong clinical responses, most frequently in patients with lung cancer, raising the possibility of adopting similar treatment strategies in patients with MET alterations in other cancer types. PATIENT AND METHODS: We describe a patient with advanced triple-negative breast cancer with a 30-fold amplification of MET. Next-generation sequencing of pre- and postprogression biopsies was performed to identify the resistance mechanism emerging after an initial exceptional response to crizotinib. The response of the resistance mutant to type I and II MET inhibitors was assessed in cultured cells. RESULTS: After progressing on crizotinib, a MET-D1228N mutation was detected, which is located in the crizotinib-binding region of the MET kinase domain. Experimental studies demonstrated that this mutation confers complete resistance to crizotinib yet retains cabozantinib sensitivity. Treatment of the patient with cabozantinib led to a subjective improvement in clinical symptoms, but the patient progressed after 7 weeks. CONCLUSION: Although MET mutations are rare in breast cancer, these patients may experience substantial clinical benefit from crizotinib treatment. Nevertheless, drug resistance owing to on-target MET mutations will likely be frequently encountered and comprehensive mechanistic studies to assess sensitivity of these mutants to a series of potential second-line therapies may help guide subsequent treatment for these patients.

Targeted mutation detection in breast cancer using MammaSeq™.

BACKGROUND: Breast cancer is the most common invasive cancer among women worldwide. Next-generation sequencing (NGS) has revolutionized the study of cancer across research labs around the globe; however, genomic testing in clinical settings remains limited. Advances in sequencing reliability, pipeline analysis, accumulation of relevant data, and the reduction of costs are rapidly increasing the feasibility of NGS-based clinical decision making. METHODS: We report the development of MammaSeq, a breast cancer-specific NGS panel, targeting 79 genes and 1369 mutations, optimized for use in primary and metastatic breast cancer. To validate the panel, 46 solid tumors and 14 plasma circulating tumor DNA (ctDNA) samples were sequenced to a mean depth of 2311× and 1820×, respectively. Variants were called using Ion Torrent Suite 4.0 and annotated with cravat CHASM. CNVKit was used to call copy number variants in the solid tumor cohort. The oncoKB Precision Oncology Database was used to identify clinically actionable variants. Droplet digital PCR was used to validate select ctDNA mutations. RESULTS: In cohorts of 46 solid tumors and 14 ctDNA samples from patients with advanced breast cancer, we identified 592 and 43 protein-coding mutations. Mutations per sample in the solid tumor cohort ranged from 1 to 128 (median 3), and the ctDNA cohort ranged from 0 to 26 (median 2.5). Copy number analysis in the solid tumor cohort identified 46 amplifications and 35 deletions. We identified 26 clinically actionable variants (levels 1-3) annotated by OncoKB, distributed across 20 out of 46 cases (40%), in the solid tumor cohort. Allele frequencies of ESR1 and FOXA1 mutations correlated with CA.27.29 levels in patient-matched blood draws. CONCLUSIONS: In solid tumor biopsies and ctDNA, MammaSeq detects clinically actionable mutations (OncoKB levels 1-3) in 22/46 (48%) solid tumors and in 4/14 (29%) of ctDNA samples. MammaSeq is a targeted panel suitable for clinically actionable mutation detection in breast cancer.

Genomic case report of a low grade bladder tumor metastasis to lung.

BACKGROUND: We present a rare case where distant metastasis of a low grade bladder tumor was observed. We carried out detailed genomic analysis and cell based experiments on patient tumor samples to study tumor evolution, possible cause of disease and provide personalized treatment strategies. CASE PRESENTATION: A man with a smoking history was diagnosed with a low-grade urothelial carcinoma of the bladder and a concurrent high-grade upper urinary tract tumor. Seven years later he had a lung metastasis. We carried out exome sequencing on all the patient's tumors and peripheral blood (germline) to identify somatic variants. We constructed a phylogenetic tree to capture how the tumors are related and to identify somatic changes important for metastasis. Although distant metastasis of low-grade bladder tumor is rare, the somatic variants in the tumors and the phylogenetic tree showed that the metastasized tumor had a mutational profile most similar to the low grade urothelial carcinoma. The primary and the metastatic tumors shared several important mutations, including in the KMT2D and the RXRA genes. The metastatic tumor also had an activating MTOR mutation, which may be important for tumor metastasis. We developed a mutational signature to understand the biologic processes responsible for tumor development. The mutational signature suggests that the tumor mutations are associated with tobacco carcinogen exposure, which is concordant with the patient's smoking history. We cultured cells from the lung metastasis to examine proliferation and signaling mechanisms in response to treatment. The mTOR inhibitor Everolimus inhibited downstream mTOR signaling and induced cytotoxicity in the metastatic tumor cells. CONCLUSION: We used genomic analysis to examine a rare case of low grade bladder tumor metastasis to distant organ (lung). Our analysis also revealed exposure to carcinogens found is tobacco as a possible cause in tumor development. We further validated that the patient might benefit from mTOR inhibition as a potential salvage therapy in an adjuvant or recurrent disease setting.

Adaptation of an amplicon-based human cancer next-generation sequencing panel assay for murine tumors.

Unlike humans, inbred genetically engineered mice have minimal inter-individual variation and, consequently, offer substantially increased statistical power for robust definition of recurrent cooperating cancer mutations. While technically feasible, whole exome sequencing is expensive and extremely data-intensive. Somatic mutation analysis using panels of 25-75 genes now provides detailed insight into the biology of human tumors. Here we report an adaptation for mouse tumors of a human PCR amplicon-based panel (Ion Torrent Cancer Hotspot Panel v2) allowing analysis of 18 cancer genes, including Kras, Nras, Hras, Pten, Pik3ca and Smad4, and encompassing regions homologous to more than 2000 known human cancer mutations.

Synchronous Bilateral Tubal Serous Carcinomas in a Patient With Exon 13 Duplication and Loss of Function of BRCA1.

We report the first case of distinct, synchronous serous carcinomas of the adnexa arising in a patient with a family history of breast and ovarian cancer and a germline loss of function mutation in BRCA1. Illustrating an exceedingly rare phenomenon of synchronous high-grade carcinomas with distinct histomorphologic, immunohistochemical and cytogenetic features, the case serves as a point of departure for the discussion of phenotypic patterns of carcinomas arising in BRCA1 mutation carriers. We also review patient management, including the importance of risk-reducing salpingo-oophorectomy in women with deleterious BRCA1 mutations, as well as the potential need for an intraoperative pathologic assessment to find occult, high-grade carcinomas in this setting.

Characterizing Molecular Variants and Clinical Utilization of Next-generation Sequencing in Advanced Breast Cancer.

Women with advanced breast carcinomas have few therapeutic options. Recent advances in genomic profiling represent a new paradigm of cancer classification and treatment, but experience with genomic testing in a clinical setting remains limited. We retrospectively determined the genomic variants and correlate these with histology [histomorphologic subtype, nuclear grade, standard immunohistochemistry (IHC)] and clinical utilization (ordering, turnaround time, report review, and targeted therapy). Among 48 patients, 2 showed no genetic alterations, 11 (23%) showed variants of unclear significance only and 35 (73%) showed variant(s) affecting function (VaF) and/or variants of unclear significance. Overall, 119 variants were observed in 20 of 50 tested genes. Each patient had a unique molecular profile, with numerous (n=58) variants not previously reported in breast cancer. VaF detected in more than 2 patients included: TP53 (n=21), PIK3CA (n=20), and FGFR1 (n=3). VaF comprised 46 single nucleotide variants (79%), 7 amplifications (12%), 3 frameshifts (5%), 1 insertion (2%), and 1 deletion (2%). The tested samples had very high Ki67 index (average 57%±23%) and approximately half were hormone receptor and HER2 negative (25/46, 54%). Metastatic breast carcinomas showed a higher average VaF versus breast-localized tumors (1.3±0.99 vs. 0.18±0.60, P<0.05). Next-generation sequencing reports were promptly reported and reviewed (average 1 to 2 d) and 7 (∼25%) of potentially eligible patients received targeted therapy. Advanced breast cancers show unique landscapes of genetic variants. Most testing was done in late disease, often in metastatic and receptor-negative carcinomas. Next-generation sequencing results were promptly reported and reviewed, but the utilization of targeted therapies was limited.

Utility of a novel triple marker (combination of thyroid transcription factor 1, Napsin A, and P40) in the subclassification of non-small cell lung carcinomas using fine-needle aspiration cases.

Personalized treatment of lung cancer requires an accurate subclassification of non-small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC), squamous cell carcinoma (SqCC), and other subtypes. In poorly differentiated tumors especially on small fine-needle aspirate specimens, the subclassification could be difficult in certain cases. Our previous study using resected tumor tissue has shown that the combination of commonly used individual markers (thyroid transcription factor 1 [TTF-1], P40, and Napsin A) into a novel triple marker has high sensitivity and specificity in subclassification of NSCLC and also the advantage of using minimal tumor tissue. In this study, we further evaluated the utility of this novel triple marker using fine-needle aspirate cases. We included primary NSCLC, consisting of 37 SqCCs (primary, 35; metastasis, 2) and 50 ADCs (primary, 29; metastasis, 21), 12 metastatic ADCs of nonpulmonary primary, and 10 small cell lung carcinomas. The immunohistochemical patterns were semiquantitatively scored. In lung SqCCs and ADCs, the sensitivity and specificity of the triple marker were 100% and 97.1% and 86.0% and 100%, respectively. The triple marker showed no immunoreactivity in 12 metastatic nonpulmonary ADCs. In 10 small cell lung carcinomas, TTF-1 had focal positivity in 40% of cases. The limitations of the triple marker include staining of alveolar macrophages (by TTF-1 and Napsin A), basal layer of bronchial epithelial cells (by P40), and nonspecific cytoplasmic staining of TTF-1. Our study not only supports our previous finding using resected tumor specimens but also provides evidence that the triple marker can be used for cytological material and preserving tumor tissue for molecular testing.

Utility of five commonly used immunohistochemical markers TTF-1, Napsin A, CK7, CK5/6 and P63 in primary and metastatic adenocarcinoma and squamous cell carcinoma of the lung: a retrospective study of 246 fine needle aspiration cases.

BACKGROUND: Fine needle aspiration (FNA) biopsy plays a critical role in the diagnosis and staging of lung primary and metastatic lung carcinoma. Accurate subclassification of adenocarcinoma (ADC) and/or squamous cell carcinoma (SqCC) is crucial for the targeted therapy. However, the distinction between ADC and SqCC may be difficult in small FNA specimens. Here, we have retrospectively evaluated the utility of TTF-1, Napsin A, CK7, P63 and CK5/6 immunohistochemical (IHC) markers in the distinguishing and subclassification of ADC and SqCC. METHODS: A total of 246 FNA cases were identified by a computer search over a two-year period, including 102 primary NSCLC and 144 primary NSCLC which had metastasized to other sites. The immunostaining patterns of TTF-1, Napsin A, CK7, P63 and CK5/6 were correlated with the histological diagnosis of the tumor. RESULTS: In 72 primary ADCs, TTF-1, Napsin A and CK7 showed a sensitivity and specificity of 84.5%/96.4%, 92.0%/100%, and 93.8%/50.0%. In 30 primary SqCCs, CK5/6 and P63 showed a sensitivity and specificity of 100%/77.8% and 91.7%/78.3%. In 131 metastatic ADCs, Napsin A showed the highest specificity (100%), versus TTF-1 (87.5%) and CK7 (25%) but decreased sensitivity (67.8% versus 86.9% and 100%); whereas in 13 metastatic SqCCs, CK5/6 and P63 showed a sensitivity/specificity of 100%/84.6% and 100%/68.4%. Bootstrap analysis showed that the combination of TTF-1/CK7, TTF-1/Napsin A and TTF-1/CK7/Napsin A had a sensitivity/specificity of 0.960/0.732, 0.858/0.934, 0.972/0.733 for primary lung ADCs and 0.992/0.642, 0.878/0.881, 0.993/0.618 for metastatic lung ADCs. CONCLUSIONS: Our study demonstrated that IHC markers had variable sensitivity and specificity in the subclassification of primary and metastatic ADC and SqCC. Based on morphological findings, an algorithm with the combination use of markers aided in the subclassification of NSCLCs in difficult cases.

Lymph node metastases of melanoma: challenges for BRAF mutation detection.

Detection of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations is required to predict response to BRAF or mitogen-activated protein kinase kinase 1 and 2 inhibitors in metastatic melanoma. Lymph node (LN) specimens carrying melanoma cells intermingled with abundant lymphocytes often contain low tumor cellularity. This study is aimed to examine challenges in the clinical detection of BRAF mutations in LN specimens with metastatic melanoma and to illustrate characteristic features of p.V600E and non-p.V600E mutations. In this retrospective study for quality assessment of the pyrosequencing assay, we compared characteristics of 53 LN and 135 non-LN formalin-fixed, paraffin-embedded specimens with metastatic melanoma submitted for BRAF mutation detection over a 40-month period. LN specimens showed a significantly higher incidence of p.V600E mutations than non-LN specimens (49% versus 22%, P < .01) but a significantly lower tumor cellularity, particularly in the case of subcapsular or infiltrative metastases. Mutant allele-specific imbalance of the p.V600E mutation was predominantly present in specimens with distant organ metastases (79% versus 27% in LN metastases versus 13% in primary cutaneous tumors or adjacent soft tissue, P < .001). p.V600K was detected in 23% of men older than 60 years old, compared with 6% in women older than 60 years old and 2% in both men and women younger than 60 years old (P < .001). LN specimens with low tumor cellularity due to numerous adjacent lymphocytes may pose a challenge to clinical detection of BRAF mutations of melanoma. The higher incidence of p.V600E mutations in LNs may prompt further studies to elucidate if the p.V600E mutation in primary tumors is associated with a higher risk of LN metastasis.

First report of Westerdykella dispersa as a cause of an angioinvasive fungal infection in a neutropenic host.

Angioinvasive fungal infections (AFIs) are an important cause of morbidity and mortality among immunocompromised patients. However, clinicomicrobiological characteristics and treatment of many AFI agents remain poorly defined. We report the first human case of infection with Westerdykella dispersa, an emergent cause of AFI, which was successfully treated in a neutropenic pediatric patient.

The use of Yes-associated protein expression in the diagnosis of persistent neonatal cholestatic liver disease.

Although physiologic jaundice of neonates is common, persistent neonatal cholestasis is life-threatening and has multiple etiologies. Among these etiologies, biliary atresia (BA) requires rapid diagnosis and treatment. In diagnosing BA, the surgical pathologist must recognize subtle histologic changes, often with only a small core liver biopsy. To aid in the differential diagnosis of neonatal cholestasis, we investigated Yes-associated protein (YAP), a regulator of organ size and bile duct development. We examined whether a YAP immunostain can highlight emerging hepatobiliary epithelium in BA (n = 28) versus other causes of persistent cholestasis (non-BA; n = 15) and thus serve as a useful diagnostic marker in persistent neonatal jaundice. We show significantly (P < .01) more high-grade (<2) fibrosis and ductular proliferation among BA versus non-BA cases. Likewise, there was significantly more high-grade (2-3/3) cytoplasmic and nuclear YAP staining in BA (97% and 89%) versus non-BA (20% and 13%). High-grade nuclear YAP staining was both sensitive (88%) and specific (87%) for the diagnosis of BA. In contrast to neonatal cholestasis, the differences in YAP localization in cholestatic/obstructed versus nonobstructed adult livers were not significant. Lastly, we found that pharmacologic inhibition of the YAP complex in both cholangiocyte and cholangiocarcinoma cell lines blocked compensatory bile duct proliferation, an early marker of BA that requires nuclear YAP expression, in a time- and dose-dependent manner. In summary, we show that YAP expression modulates both bile duct proliferation and liver damage/fibrosis while acting as a sensitive and specific marker in the differential diagnosis of persistent neonatal cholestasis.

Tumor cellularity as a quality assurance measure for accurate clinical detection of BRAF mutations in melanoma.

BACKGROUND: Detection of BRAF mutations is an established standard of care to predict small-molecule inhibitor (vemurafenib) response in metastatic melanoma. Molecular assays should be designed to detect not only the most common p.V600E mutation, but also p.V600K and other non-p.V600E mutations. OBJECTIVE: The purpose of this study was to assess if tumor cellularity can function as a quality assurance (QA) measure in molecular diagnostics. Potential causes of discrepancy between the observed and predicted mutant allele percentage were also explored. METHODS: We correlated pathologist-generated estimates of tumor cellularity versus mutant allele percentage via pyrosequencing as a QA measure for BRAF mutation detection in formalin-fixed, paraffin-embedded melanoma specimens. RESULTS: BRAF mutations were seen in 27/62 (44 %) specimens, with 93 % p.V600E and 7 % non-p.V600E. Correlation between p.V600E mutant percentage and tumor cellularity was poor-moderate (r = -0.02; p = 0.8), primarily because six samples showed a low p.V600E signal despite high tumor cellularity. A QA investigation revealed that our initial pyrosequencing assay showed a false positive, weak p.V600E signal in specimens with a p.V600K mutation. A redesigned assay detected BRAF mutations in 50/131 (38 %) specimens, including 30 % non-p.V600E. This revised assay showed strong correlation between p.V600E BRAF mutant percentage and tumor cellularity (r = 0.76; p ≤ 0.01). Re-evaluation of the previously discordant samples by the revised assay confirmed a high level of p.V600K mutation in five specimens. CONCLUSIONS: Pathologists play important roles in molecular diagnostics, beyond identification of correct cells for testing. Accurate evaluation of tumor cellularity not only ensures sufficient material for required analytic sensitivity, but also provides an independent QA measure of the molecular assays.

Ki-67 index as an ancillary tool in the differential diagnosis of proliferative endometrial lesions with secretory change.

"Secretory change" can accompany a variety of proliferative endometrial lesions, ranging from hyperplasia to carcinoma. It is characterized by subnuclear or supranuclear vacuolization, mimicking early secretory endometrium (SEM). As an additional diagnostic challenge, mitotic activity and cytologic atypia are often low in hyperplastic lesions with secretory change. As mitotic activity in lesions with secretory change is decreased, the mitotic index may not be useful to distinguish SEM with glandular crowding from hyperplasia with secretory change. We therefore hypothesized that Ki-67 immunohistochemistry, an alternative marker of proliferative activity, might be useful in this setting. Forty-four endometrial lesions with secretory change and 30 controls were stained for Ki-67. Three "hot spot" areas per case were photographed and 200 to 300 cells were manually counted to obtain the ratio of Ki-67-positive cells versus total cells. A second pathologist performed an independent review of the same preselected fields and estimates without preselection. There was an incremental increase in the Ki-67 index from 2.6% in SEM to 17% in nonatypical hyperplasia, 36% in atypical hyperplasia, and 60% in endometrial carcinoma. The Ki-67 index for SEM was significantly (P<0.01) lower than hyperplastic lesions and carcinoma with secretory change. Similar, statistically significant results were obtained by independent estimates of Ki-67 immunopositivity. In the setting of secretory morphology, the Ki-67 index was highly sensitive and specific (>90%) for the differential diagnosis of SEM with crowding versus nonatypical hyperplasia, atypical hyperplasia, and endometrial carcinoma. In summary, the Ki-67-labeling index is a useful technique to distinguish SEM with crowding, an exaggerated physiological condition, from cancer precursors.

Intraductal tubulopapillary neoplasm of the pancreas on fine needle aspiration: case report with differential diagnosis.

Intraductal tubulopapillary neoplasm (ITPN) is a rare primary pancreatic neoplasm accounting for less than 1% of all pancreatic exocrine neoplasms and 3% of intraductal neoplasms of the pancreas. Data on this entity are still limited. Here, we report a case of ITPN with cytopathologic and histopathologic findings. A 41-year-old woman with a 2.2 cm cyst in the head of the pancreas for five years was referred to our institution. The endoscopic ultrasound-guided fine-needle aspiration produced cytospins were moderately cellular with a few fragments of markedly atypical epithelium. The neoplastic cells displayed high-grade nuclear atypia with enlarged, eccentric nuclei, anisonucleosis and prominent nucleoli, irregular nuclear membranes, high nucleus to cytoplasmic (N/C) ratios, and a moderate amount of cytoplasm with no intracytoplasmic mucin. Histologically, the lesion was found to be an ITPN with focal high-grade dysplasia. No invasive carcinoma was identified. The neoplastic cells exhibited luminal immunolabeling for MUC-1, but were negative for MUC-2, trypsin, chymotrypsin, and P53. Approximately 5% of the neoplastic cells showed Ki-67 immunoreactivity. ITPN of pancreas may be a source of markedly atypical epithelial cells in pancreatic cystic aspiration. Clinical and radiographic findings, molecular mutational analysis, in combination with cytological features are essential to differentiate it from other disease entities.

Sacrococcygeal teratomas: clinico-pathological characteristics and isochromosome 12p status.

The biological behavior of teratomas is highly variable, and morphologic features alone are insufficient to predict their clinical course. Prognostic factors that influence behavior include the following: patient sex, age, anatomic site, coincident neoplasm, and cytogenetic abnormalities. Gonadal teratomas have been well-characterized; postpubertal testicular teratomas are commonly associated with isochromosome 12p (i12p) and considered to nearly always carry a potential for malignant behavior, whereas ovarian and prepubertal testicular teratomas are i12p negative and predominantly benign in behavior. For extragonadal sites, such as sacrum and coccyx, clinical characteristics and i12p status are yet to be adequately characterized. As part of this study, we identified 19 sacrococcygeal teratomas in our surgical pathology archives from 1990 to 2012. Clinical records and slides were reviewed to confirm the original diagnosis. Gains in chromosome 12p, including i12p status were assessed in representative paraffin sections by fluorescence in situ hybridization. Our cases included 16 mature sacrococcygeal teratomas (11 prepubertal and 5 postpubertal) and three immature saccrococygeal teratomas (all prepubertal). Among mature teratomas, the average tumor size was larger in adults compared with prepubertal patients. A higher number of adult cases were recurrences (80% vs 21%), but only pediatric recurrences were managed with postoperative chemotherapy. All examined tumors were negative for i12p. 100% survival was documented in our cohort with a median follow-up of 6 years. We present a large series of sacrococcygeal teratomas and the first series to examine postpubertal adults at this anatomic site. All tumors lacked chromosome 12p gains, including i12p. Both pre- and postpubertal sacrococcygeal teratomas had a favorable outcome regardless of age or sex.

Renal cell carcinoma presenting with brain metastasis from a 1.6 cm primary tumor.

Small renal cell carcinoma (RCC) tumors are believed to have a negligible risk of metastasis. We report on a 77-year-old man presenting with extremity weakness who was found to have a 2.5 cm brain metastasis from a subsequently discovered 1.6 cm clear cell RCC primary tumor. We review what is known about synchronous and metachronous metastasis from small renal tumors and prognostic features informing treatment for such lesions.