A New Method of Identifying Pathologic Complete Response After Neoadjuvant Chemotherapy for Breast Cancer Patients Using a Population-Based Electronic Medical Record System.

BACKGROUND: Accurate identification of pathologic complete response (pCR) from population-based electronic narrative data in a timely and cost-efficient manner is critical. This study aimed to derive and validate a set of natural language processing (NLP)-based machine-learning algorithms to capture pCR from surgical pathology reports of breast cancer patients who underwent neoadjuvant chemotherapy (NAC). METHODS: This retrospective cohort study included all invasive breast cancer patients who underwent NAC and subsequent curative-intent surgery during their admission at all four tertiary acute care hospitals in Calgary, Alberta, Canada, between 1 January 2010 and 31 December 2017. Surgical pathology reports were extracted and processed with NLP. Decision tree classifiers were constructed and validated against chart review results. Machine-learning algorithms were evaluated with a performance matrix including sensitivity, specificity, positive predictive value (PPV), negative predictive value [NPV], accuracy, area under the receiver operating characteristic curve [AUC], and F1 score. RESULTS: The study included 351 female patients. Of these patients, 102 (29%) achieved pCR after NAC. The high-sensitivity model achieved a sensitivity of 90.5% (95% confidence interval [CI], 69.6-98.9%), a PPV of 76% (95% CI, 59.6-87.2), an accuracy of 88.6% (95% CI, 78.7-94.9%), an AUC of 0.891 (95% CI, 0.795-0.987), and an F1 score of 82.61. The high-PPV algorithm reached a sensitivity of 85.7% (95% CI, 63.7-97%), a PPV of 81.8% (95% CI, 63.4-92.1%), an accuracy of 90% (95% CI, 80.5-95.9%), an AUC of 0.888 (95% CI, 0.790-0.985), and an F1 score of 83.72. The high-F1 score algorithm obtained a performance equivalent to that of the high-PPV algorithm. CONCLUSION: The developed algorithms demonstrated excellent accuracy in identifying pCR from surgical pathology reports of breast cancer patients who received NAC treatment.

Kikuchi-Fujimoto lymphadenitis imitating metastatic melanoma on positron emission tomography: a case report.

BACKGROUND: Accurate staging is critical for decision-making for the treatment of malignant conditions. Fluoro-deoxy-glucose positron emission tomography-computed tomography (FDG PET-CT) is a highly sensitive imaging modality for the assessment of distant metastases; however false positive results are possible due to its lower specificity with detection of other hypermetabolic pathologies. CASE PRESENTATION: A patient with high-risk thigh melanoma was staged with FDG PET-CT. Four ipsilateral inguinal nodes (three superficial, one deep) demonstrated intense hypermetabolic activity. Metastatic melanoma was confirmed in the largest superficial inguinal node with ultrasound-guided fine needle aspiration. Histopathology demonstrated metastatic melanoma in one superficial node and histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease in five deep inguinal nodes. CONCLUSION: This case illustrates a false positive FDG PET-CT due to coincidental, synchronous melanoma and Kikuchi-Fujimoto disease in the same draining lymph node basin.

Malignancy is in the eye of the beholder: Pathologic diagnosis of challenging follicular neoplasms in the era of noninvasive follicular thyroid neoplasms with papillary-like nuclear features and immunohistochemical and molecular adjuncts.

BACKGROUND: Classification of thyroid follicular neoplasms can be challenging for pathologists. Introduction of noninvasive follicular thyroid neoplasms with papillary-like nuclear features, the utilization of immunohistochemistry, and molecular analysis are all thought to be valuable diagnostic adjuncts. Our aim was to determine whether interobserver variability for follicular neoplasms has improved since the application of these adjuncts. METHODS: One representative section from a cohort of follicular neoplasms previously proven difficult for pathologists were examined independently by 7 pathologists and assigned to 1 of 3 diagnostic categories (benign, neoplasms with papillary-like nuclear features, or malignant). This process was carried out separately 3 times: (1) after viewing hematoxylin and eosin stain slides, (2) hematoxylin and eosin stain in conjunction with immunohistochemistry, and (3) hematoxylin and eosin stain/immunohistochemistry in conjunction with molecular analysis. The interobserver variability and overall agreement were then calculated using the free-marginal kappa coefficient. RESULTS: Agreement on hematoxylin and eosin stain was 57%, with a kappa coefficient of 0.36 (minimal agreement). The agreement improved slightly with the application of immunohistochemistry (kappa coefficient = 0.49 [weak agreement] and a percentage agreement 67%). The level of agreement decreased slightly after the addition of molecular analysis (kappa coefficient = 0.43 [weak agreement] and percentage agreement 62%). CONCLUSION: Despite attempts to standardize the diagnostic criteria for neoplasms with papillary-like nuclear features and the utilization immunohistochemistry and molecular analysis, attaining pathologic consensus for difficult follicular neoplasms of the thyroid remains a challenge.

An Unusual Case of Pancreatic Metastasis from Squamous Cell Carcinoma of the Lung Diagnosed by EUS-Guided Fine Needle Biopsy.

We report a case of a 70-year-old man who presented with abdominal pain and weight loss, with initial imaging showing simultaneous mass lesions in the pancreas and lungs along with extensive lymphadenopathy in the thorax up to the left supraclavicular region. Core biopsies of the left supraclavicular lymph node showed squamous cell carcinoma, which required differentiation between secondary and primary pancreatic neoplasms. Endoscopic ultrasound-guided sampling using a novel fine needle biopsy system was key to making a definite histological diagnosis and determining the best treatment plan.

Myelofibrotic transformations of polycythemia vera and essential thrombocythemia are morphologically, biologically, and prognostically indistinguishable from primary myelofibrosis.

A fraction of polycythemia vera (PV) and essential thrombocythemia (ET) cases will, in time, undergo myelofibrotic transformation. In such cases, fibrosis may mask the diagnostic histologic features of the original underlying myeloproliferative neoplasm. Thus, confidently differentiating postfibrotic PV/ET from primary myelofibrosis (PMF) histologically may not be possible. It is controversial whether post-PV/ET myelofibrosis (MF) differs clinicopathologically from PMF, or whether these entities are biologically, clinically, and prognostically indistinguishable. To answer this question, we compared multiple candidate biological, morphologic, and prognostic parameters between 19 postfibrotic ET/PV individuals and 18 PMF individuals. The postfibrotic ET/PV and PMF cases did not differ with regard to clinical outcome, cytogenetic abnormalities, serum lactate dehydrogenase level, peripheral blast count, bone marrow morphology, or grade of reticulin fibrosis. Only JAK2 allele burden, which was higher in the postfibrotic PV/ET population (P=0.011), differed between the 2 groups. Cardinal morphologic features of PMF (ie, marrow cellularity, intrasinusoidal hematopoiesis, osteosclerosis, etc.) were commonly observed in post-PV/ET MF marrow biopsies, and only a minority of post-PV/ET MF marrow biopsies the retained diagnostic features of the primary myeloproliferative neoplasm (panmyelosis in PV and megakaryocytic hyperplasia in ET). Our study indicates that PMF and post-PV/ET MF are clinically and biologically indistinguishable.

Merkel cell polyomavirus (MCPyV) in chronic lymphocytic leukemia/small lymphocytic lymphoma.

Merkel cell polyomavirus (MCPyV) is a novel polyomavirus that shows a strong association with Merkel cell carcinoma (MCC). Recent studies have demonstrated MCPyV in some cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), a malignancy with a similar demographic as MCC. We tested for the presence of MCPyV by PCR and immunohistochemistry in 18 cases of CLL/SLL. Very low-level MCPyV DNA was detected in 33% of CLL/SLL cases by real-time PCR, but only one case demonstrated immunohistochemical positivity for MCPyV. MCPyV was not identified in 17 cases of follicular lymphoma, suggesting either that MCPyV is involved in CLL/SLL pathogenesis or that the immunodeficiency state of CLL/SLL induces low-level MCPyV reactivation.

Composite mantle cell and diffuse large B-cell lymphoma: report of two cases.

Composite lymphomas are rare and involve the concurrent evolution of 2 distinct lymphoma types within a single organ or tissue. This study describes 2 cases of composite mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL), which has not previously been reported. Each case demonstrated distinct populations of CD20 positive small and large atypical B cells. In both cases, only the small lymphocytes were positive for CD5 and cyclin D1, and fluorescence in situ hybridization (FISH) showed a t(11;14) translocation in the small lymphocytes but not in the large cells. Molecular studies for B-cell clonality showed a possible clonal relationship between the 2 components in one case but not the other. This study describes in detail the morphology, immunophenotype, FISH, and molecular analysis of both components in each case. To the authors' knowledge, this represents the first report of juxtaposition of MCL with DLBCL that does not represent transformation of the mantle cell component.

Quantification of fibrosis and osteosclerosis in myeloproliferative neoplasms: a computer-assisted image study.

Evaluation of bone marrow fibrosis and osteosclerosis in myeloproliferative neoplasms (MPN) is subject to interobserver inconsistency. Performance data for currently utilized fibrosis grading systems are lacking, and classification scales for osteosclerosis do not exist. Digital imaging can serve as a quantification method for fibrosis and osteosclerosis. We used digital imaging techniques for trabecular area assessment and reticulin fiber quantification. Patients with all Philadelphia negative MPN subtypes had higher trabecular volume than controls (p