Association between Hyperprolactinemia and Granulomatous Mastitis.

Granulomatous mastitis (GM) is a relatively uncommon inflammatory breast lesion with multiple suggested etiologies. Although most GM cases show association with lactation and pregnancy, a minority of cases have been linked to hyperprolactinemia caused by either dopamine antagonist medications or with intracranial lesions, such as pituitary adenoma. The goal of this study is to review the GM cases reported in the literature with a specific emphasis on those cases associated with hyperprolactinemia and prolactinomas and to identify cases of GM seen at the Cleveland Clinic Florida which demonstrate co-occurrences of GM and intracranial lesions. CoPath and Epic data bases at Cleveland Clinic Florida were searched for cases describing inflammatory breast lesions in patients with pituitary pathology. Chart reviews were conducted and pertinent medical history was extracted for case reports. H&E-stained paraffin-embedded sections retrieved from Cleveland Clinic Florida pathology storage were evaluated by light microscopy. Four cases showing a co-occurrence of GM and hyperprolactinemia were consequently identified. A prolactin-secreting pituitary adenoma was present in two of the three GM cases. The third case demonstrated a concomitant craniopharyngioma, which was also associated with a rise in serum prolactin. This phenomenon was presumably attributable to compression, resulting in compromised transport of dopamine to the adenohypophysis and subsequent disinhibition of prolactin secretion by lactotrophs. The fourth patient with GM had a similar history of elevated prolactin. Classical histopathological features of GM were found in all four cases, including noncaseating granulomas, multinucleated giant cells, epithelioid histiocytes, and chronic inflammation. Intriguingly, complete resolution of inflammatory breast lesions along with normalization of prolactin levels occurred following the surgical excision of the craniopharyngioma, suggesting that intracranial lesion-induced hyperprolactinemia might be directly causal in GM. Therefore, the authors would suggest screening for pituitary tumors and evaluate prolactin levels in the workup of GM patients without a recent history of lactation and pregnancy and no other identified etiology.

Undetectable Thyroglobulin Levels in Poorly Differentiated Thyroid Carcinoma Patients Free of Macroscopic Disease After Initial Treatment: Are They Useful?

BACKGROUND: Predictive role of undetectable thyroglobulin (Tg) in patients with poorly differentiated thyroid carcinoma (PDTC) is unclear. Our goal was to report on Tg levels following total thyroidectomy and adjuvant RAI in PDTC patients and to correlate Tg levels with recurrence. METHODS: Forty patients with PDTC with no distant metastases at presentation (M0) and managed by total thyroidectomy and adjuvant RAI were identified from a database of 91 PDTC patients. Of these, 31 patients had Tg values recorded and formed the basis of our analysis. A nonstimulated Tg level <1 ng/ml was used as a cutoff point for undetectable Tg levels. Association of patient and tumor characteristics with Tg levels was examined by χ (2) test. Recurrence-free survival (RFS) stratified by postop Tg level was calculated by Kaplan-Meier method and compared by log-rank test. RESULTS: Twenty patients had undetectable Tg (<1 ng/ml) and 11 had detectable Tg (≥1 ng/ml; range 2-129 ng/ml) following surgery. After adjuvant RAI, 24 patients had undetectable Tg (<1 ng/ml) and 7 had detectable Tg (≥1 ng/ml; range 1-57 ng/ml). Patients with undetectable Tg were less likely to have pathologically positive margins compared to those with detectable Tg (33 vs. 72 % respectively; p = 0.03). Patients with undetectable Tg levels had better 5-year regional control and distant control than patients with detectable Tg level (5-year regional recurrence-free survival 96 vs. 69 %; p = 0.03; 5-year distant recurrence-free survival 96 vs. 46 %, p = 0.11). CONCLUSION: Postoperative thyroglobulin levels in subset of patients with PDTC appear to have predictive value for recurrence. Patients with undetectable Tg have a low rate of recurrence.

Long-term regional control and survival in patients with "low-risk," early stage oral tongue cancer managed by partial glossectomy and neck dissection without postoperative radiation: the importance of tumor thickness.

BACKGROUND: The objectives of this study were to determine the incidence of locoregional failure in patients with low-risk, early stage oral tongue squamous cell cancer (OTSCC) who undergo partial glossectomy and ipsilateral elective neck dissection without receiving postoperative radiation. METHODS: A combined database of patients with OTSCC who received treatment at Memorial Sloan-Kettering Cancer Center and Princess Margaret Cancer Center from 1985 to 2005 was established. In total, 164 patients with pathologic T1-T2N0 OTSCC who underwent partial glossectomy and ipsilateral elective neck dissection without postoperative radiation were identified. Patient-related, tumor-related, and treatment-related characteristics were recorded. Local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were calculated by the Kaplan-Meier method. Predictors of outcome were analyzed by univariate and multivariate analysis. RESULTS: At a median follow-up of 66 months (range 1-171 months), the 5-year rates of local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were 89%, 79.9%, and 85.6%, respectively. Regional recurrence was ipsilateral in 61% of patients and contralateral in 39% of patients. The regional recurrence rate was 5.7% for tumors <4 mm and 24% for tumors ≥ 4 mm. Multivariate analysis indicated that tumor thickness was the only independent predictor of neck failure (regional recurrence-free survival, 94% vs 72% [P = .02] for tumors <4 mm vs ≥ 4 mm, respectively). Patients who developed recurrence in the neck had a significantly poorer disease-specific survival compared with those who did not (33% vs 97%; P < .0001). CONCLUSIONS: Patients with low-risk, pathologic T1-T2N0 OTSCC had a greater than expected rate of neck failure, with contralateral recurrence accounting for close to 40% of recurrences. Failure occurred predominantly in patients who had primary tumors that were ≥ 4 mm thick.

Clinical and Pathologic Features Associated With Invasive Breast Carcinoma With 2018 American Society of Clinical Oncology/College of American Pathologists In Situ Hybridization Group 2 Results (Human Epidermal Growth Factor Receptor 2 [HER2]/Chromosome 17 Centromere [CEP17] Ratio ≥2.0 and Average HER2 Copy Number <4.0).

CONTEXT.­: The American Society of Clinical Oncology/College of American Pathologists updated the human epidermal growth factor receptor 2 (HER2) breast carcinoma testing guideline in 2018 to address issues from uncommon HER2 fluorescence in situ hybridization (FISH) results. Based on the 2013 American Society of Clinical Oncology/College of American Pathologists guideline, cases wherein the HER2/chromosome 17 centromere (CEP17) ratio of 2.0 or more with an average HER2 copy number of less than 4.0 were considered in situ hybridization (ISH) positive. Under the 2018 guideline, such cases are classified as ISH Group 2 and are no longer considered eligible for anti-HER2 therapy when the corresponding HER2 immunohistochemistry result is 0, 1+, or 2+. OBJECTIVE.­: To assess the clinical, pathologic, and treatment aspects of patients with ISH Group 2 results. DESIGN.­: We retrospectively reviewed HER2 FISH results at our center between January 2012 and December 2014 and identified and characterized cases with ISH Group 2 results. RESULTS.­: Thirty-nine cases with ISH Group 2 results from 39 patients were reviewed. Twenty of 39 (51%) patients received anti-HER2 therapy. Patients treated with HER2-targeted therapy were less likely to have hormone receptor-positive tumors, compared with patients without anti-HER2 treatment, though not significantly (P = .30). The only significant difference between the 2 patient groups was receipt of cytotoxic chemotherapy treatment (P < .001). Overall, clinical outcome was similar between the 2 groups (P > .99). CONCLUSIONS.­: This retrospective study with median follow-up of at least 6 years shows patients with ISH Group 2 tumors had similar clinical outcomes, irrespective of HER2-targeted therapy. Further analysis in the prospective setting would provide valuable data that would potentially inform clinical decision making.

Sinonasal adenocarcinoma: a rare second malignancy in long term retinoblastoma survivors.

Retinoblastoma is the most common primary cancer of the eye in children. The incidence of second tumors in survivors of bilateral retinoblastoma and in survivors of unilateral retinoblastoma who presumably carry a germline RB1 mutation is documented. This article describes the previously unrecognized association of sinonasal adenocarcinoma as a second malignancy in retinoblastoma survivors. We present three cases who received radiation therapy as a part of their treatment and developed sinonasal adenocarcinoma as a second malignancy. Sinonasal adenocarcinoma should be considered as a second malignancy in retinoblastoma survivors who present with vague sinus symptoms.

Adenocarcinoma of the upper aerodigestive tract.

Although squamous cell carcinoma is the most frequent malignant diagnosis made with upper aerodigestive tract specimens, a myriad of neoplasms can occur throughout the area. Very uncommonly, one encounters adenocarcinomas that cannot be better classified as salivary gland-type neoplasia. This manuscript reviews these tumors, including sinonasal intestinal-type adenocarcinomas, sinonasal low-grade and high-grade nonintestinal adenocarcinomas and nasopharyngeal papillary adenocarcinomas. Clinical, histologic, and immunohistochemical features and differential diagnoses are discussed.

Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators by oligonucleotide microarray analysis.

BACKGROUND: The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling. METHODS: The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa were grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, GLUT3, HSAL2, and PACE4, were selected for their potential biological significance in a larger cohort of 49 patients via quantitative real-time RT-PCR. RESULTS: Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, MMP-1 encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of GLUT3, HSAL2 and PACE4, respectively. Univariate analyses demonstrated that GLUT3 over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). HSAL2 was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.047). In survival studies, only GLUT3 showed a prognostic value with disease-free (P=0.049), relapse-free (P=0.002) and overall survival (P=0.003). PACE4 mRNA expression failed to show correlation with any of the relevant parameters. CONCLUSION: The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.

Data Set for the Reporting of Nodal Excisions and Neck Dissection Specimens for Head and Neck Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

Standardized, synoptic pathologic reporting for tumors greatly improves communication among clinicians, patients, and researchers, supporting prognostication and comparison about patient outcomes across institutions and countries. The International Collaboration on Cancer Reporting is a nonprofit organization whose mission is to develop evidence-based, universally available surgical pathology reporting data sets. Within the head and neck region, lymph node excisions and neck dissections are frequently performed as part of the management of head and neck cancers arising from the mucosal sites (sinonasal tract, nasopharynx, oropharynx, hypopharynx, oral cavity, and larynx) along with bone tumors, skin cancers, melanomas, and other tumor categories. The type of specimen, exact location (lymph node level), laterality, and orientation (by suture or diagram) are essential to accurate classification. There are significant staging differences for each anatomic site within the head and neck when lymph node sampling is considered, most importantly related to human papillomavirus-associated oropharyngeal carcinomas and mucosal melanomas. Number, size, and site of affected lymph nodes, including guidelines on determining the size of tumor deposits and the presence of extranodal extension and soft tissue metastasis, are presented in the context of prognostication. This review elaborates on each of the elements included in the data set for Nodal Excisions and Neck Dissection Specimens for Head & Neck Tumours.

Data Set for the Reporting of Carcinomas of the Nasopharynx and Oropharynx: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

The International Collaboration on Cancer Reporting was established to internationally unify and standardize the pathologic reporting of cancers based on collected evidence, as well as to allow systematic data collection across institutions and countries to guide cancer care in the future. An expert panel was convened to identify the minimum data set of elements that should be included in cancer reporting from tumors of the nasopharynx and oropharynx. Specifically, there has been a significant change in practice as a result of identifying oncogenic viruses, including human papillomavirus and Epstein-Barr virus, because they preferentially affect the oropharynx and nasopharynx, respectively. For these anatomic sites, when viral association is taken into account, usually reported elements of in situ versus invasive tumor, depth of invasion, and degree of differentiation are no longer applicable. Thus, guidance about human papillomavirus testing in oropharyngeal carcinomas and Epstein-Barr virus testing in nasopharyngeal carcinomas is highlighted. Further, the clinical and the pathologic differences in staging as proposed by the 8th edition of the Union for International Cancer Control are incorporated into the discussion, pointing out several areas of continued study and further elaboration. A summary of the International Collaboration on Cancer Reporting guidelines for oropharyngeal and nasopharyngeal carcinomas is presented, along with discussion of the salient evidence and practical issues.

Osteonecrosis of the maxilla and mandible in patients with advanced cancer treated with bisphosphonate therapy.

Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing frequency over the past 5 years. ONJ is most often identified in patients with cancer who are receiving intravenous bisphosphonate (IVBP) therapy, but it has also been diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions. To further categorize risk factors associated with ONJ and potential clinical outcomes of this condition, we performed a retrospective study of patients with metastatic bone disease treated with intravenous bisphosphonates who have been evaluated by the Memorial Sloan-Kettering Cancer Center Dental Service between January 1, 1996 and January 31, 2006. We identified 310 patients who met these criteria. Twenty-eight patients were identified as having ONJ at presentation to the Dental Service and an additional 7 patients were subsequently diagnosed with ONJ. Statistically significant factors associated with increased likelihood of ONJ included type of cancer, duration of bisphosphonate therapy, sequential IVBP treatment with pamidronate followed by zoledronic acid, comorbid osteoarthritis or rheumatoid arthritis, and benign hematologic conditions. Our data do not support corticosteroid use or oral health as a predictor of risk for ONJ. Clinical outcomes of patients with ONJ were variable with 11 patients demonstrating improvement or healing with conservative management. Our ONJ experience is presented here.

Teratocarcinosarcoma of the nasal cavity and paranasal sinuses: report of 3 cases with assessment for chromosome 12p status.

Sinonasal teratocarcinosarcoma (SNTCS) is a rare malignant neoplasm with 63 reported cases to date. Patients are exclusively adults, with a mean age of 60 years and marked male predominance. Histologically, these tumors are characterized by the presence of admixed epithelial and mesenchymal components. The histogenesis of SNTCS remains uncertain and genetic studies have not been reported to date. Two SNTCSs from the archives of Memorial Sloan-Kettering Cancer Center and one submitted from St Luke's-Roosevelt Hospital Center were evaluated by fluorescent in situ hybridization for amplification of chromosome12p, an event usually associated with the genesis of bona fide germ cell neoplasms (including mediastinal and testicular teratomas). Microscopic examination revealed admixed epithelial and mesenchymal elements in all 3 cases; benign squamous and glandular epithelium and neuroepithelial tissue were identified, the squamous epithelium demonstrating "fetal-like" cytoplasmic clearing. Mesenchymal proliferations were recognized ranging from well-differentiated smooth muscle to high-grade sarcoma. A malignant germ cell component was not identified in any of the cases. Fluorescent in situ hybridization evaluation demonstrated only 2 copies of chromosome 12 per case. Although the histogenesis of SNTCS remains uncertain, we have found an absence of 12p amplification in 3 cases. Our findings suggest that 12p amplification, if it occurs at all in this setting, is exceptional and that SNTCS is a somatic-type neoplasm exhibiting divergent differentiation rather than a germ cell tumor.

Meningioma of the mandible: imaging with CT.

We present the first description of CT of a meningioma of the mandible in the literature. Extracranial meningiomas are exceedingly rare. There have been 3 cases of meningioma of the mandible described in the literature, but none characterized with cross-sectional imaging. We describe the clinical and CT features used to establish the diagnosis as well as how to differentiate this lesion from other pathology of the mandible.

Tall cell variant of papillary thyroid carcinoma without extrathyroid extension: biologic behavior and clinical implications.

BACKGROUND: The tall cell variant (TCV) is a histologic subtype of papillary thyroid carcinoma (PTC) that is more aggressive than "classical" PTC. Most authors believe that TCV's worse prognosis is related to older age at presentation, larger tumor size, and high frequency of extrathyroid tumor extension (ETE). To assess the biologic and clinical behavior of TCV without ETE, we performed a detailed comparative clinicopathologic analysis of classical PTC and TCV without ETE. METHODS: TCV was defined as a PTC harboring >50% tall cells, while classical PTC was restricted to those tumors containing >1% papillae and <30% tall cells. Microscopic analysis and chart review identified 62 cases of TCV and 83 classical PTC without ETE. These patients were analyzed for various pathologic, imaging, and clinical parameters including outcome. RESULTS: There was no statistical difference between TCV and classical PTC in relation to age, gender, tumor size, risk stratification, type of therapy, and length of follow-up. TCV displayed more invasion of the tumor capsule and more often infiltrated into the thyroid capsule (p = 0.047 and 0.0004, respectively). Among patients with microscopically assessable regional lymph node (LN), 33 of 49 (67.3%) patients with TCV had LN metastasis at presentation, while only 24 of 60 (40%) classical PTC had positive nodes (p = 0.004). In multivariate analysis, histologic subtype (TCV vs. classical PTC) was the only independent factor associated with LN metastases (p = 0.007). In patients with adequate follow-up, 4 of 62 (6.5%) classical PTC and 7 of the 47 (14.9%) TCV had thyroid cancer recurrence (p = 0.202). TCV recurred at a distant site (3 of 47, 6.4%) while none of the 62 classical PTC developed distant metastases (p = 0.077). CONCLUSION: TCV without ETE is biologically a more aggressive tumor than classical PTC without ETE independent of age, gender, and tumor size.

Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence.

Purpose: Patients with anaplastic thyroid cancer (ATC) have a very high death rate. In contrast, deaths from non-anaplastic thyroid (NAT) cancer are much less common. The genetic alterations in fatal NAT cancers have not been reported.Experimental Design: We performed next-generation sequencing of 410 cancer genes from 57 fatal NAT primary cancers. Results were compared with The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTCs) and to the genomic changes reported in ATC.Results: There was a very high prevalence of TERT promoter mutations, comparable with that of ATC, and these co-occurred with BRAF and RAS mutations. A high incidence of chromosome 1q gain was seen highlighting its importance in tumor aggressiveness. Two novel fusion genes DLG5-RET and OSBPL1A-BRAF were identified. There was a high frequency of mutations in MED12 and these were mutually exclusive to TERT promoter mutations and also to BRAF and RAS mutations. In addition, a high frequency of mutations in RBM10 was identified and these co-occurred with RAS mutations and PIK3CA mutations. Compared with the PTCs in TCGA, there were higher frequencies of mutations in TP53, POLE, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases.Conclusions: These data support a model, whereby fatal NAT cancers arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities. The high rate of TERT promoter mutations, MED12 mutations, RBM10 mutations, and chromosome 1q gain highlight their likely association with tumor virulence. Clin Cancer Res; 23(19); 5970-80. ©2017 AACR.

18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged N0 by clinical examination and CT/MRI.

UNLABELLED: (18)F-FDG PET has a high accuracy in staging head and neck cancer, but its role in patients with clinically and radiographically negative necks (N0) is less clear. In particular, the value of combined PET/CT has not been determined in this group of patients. METHODS: In a prospective study, 31 patients with oral cancer and no evidence of lymph node metastases by clinical examination or CT/MRI underwent (18)F-FDG PET/CT before elective neck dissection. PET/CT findings were recorded by neck side (left or right) and lymph node level. PET/CT findings were compared with histopathology of dissected nodes, which was the standard of reference. RESULTS: Elective neck dissections (26 unilateral, 5 bilateral; a total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of 765 dissected lymph nodes harbored metastases. Histopathology revealed nodal metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The 3 false-negative findings occurred in metastases smaller than 3 mm or because of inability to distinguish between primary tumor and adjacent metastasis. TP and false-positive nodes exhibited similar standardized uptakes (4.8 +/- 1.1 vs. 4.2 +/- 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on the basis of neck sides and 67% and 95% on the basis of number of nodal levels, respectively. If a decision regarding the need for neck dissection had been based solely on PET/CT, 3 false-negative necks would have been undertreated, and 4 false-positive necks would have been overtreated. CONCLUSION: (18)F-FDG PET/CT can identify lymph node metastases in a segment of patients with oral cancer and N0 neck. A negative test can exclude metastatic deposits with high specificity. Despite reasonably high overall accuracy, however, the clinical application of PET/CT in the N0 neck may be limited by the combination of limited sensitivity for small metastatic deposits and a relatively high number of false-positive findings. The surgical management of the N0 neck should therefore not be based on PET/CT findings alone.

Extranodal follicular dendritic cell sarcoma: clinical, pathologic, and histogenetic characteristics of an underrecognized disease entity.

It has been more than 10 years since follicular dendritic cell (FDC) sarcoma was first reported to occur in extranodal sites, yet extranodal FDC sarcoma still appears underrecognized, and its clinical and pathological characteristics remain to be defined. This study analyzed the clinical and pathological findings of three such cases that the authors encountered recently and 43 previously reported cases identified in the literature. Assessment of all 46 cases showed a slight female predominance (1.2:1) with a median age of 41.5 years. One-third of the cases were misdiagnosed at initial evaluation mainly because the possibility of FDC sarcoma was not considered. When considered, this disease had distinct pathological characteristics that allowed an accurate diagnosis. Staining for FDC markers, CD21, CD35, and clusterin was particularly helpful. The pathogenesis of the disease appeared heterogeneous, and associated factors included Epstein-Barr virus infection (in hepatic cases) and inflammatory pseudotumor-like conditions. Treatment modality varied widely although surgical resection was often included. With a median follow-up of 18 months, 43% of the cases recurred and 7% died of disease. The 5-year recurrence-free survival was 27.4%. From data available at the current time, we were not able to identify prognostically significant pathologic factors.

Giant cystic degeneration of a uterine leiomyoma in a patient with autosomal dominant polycystic kidney disease.

OBJECTIVE: To report the management of a large uterine leiomyoma with diffuse cystic degeneration in a patient with autosomal dominant polycystic kidney disease (ADPKD). DESIGN: Case Report. SETTING: Cleveland Clinic Florida, Department of Gynecology, Section of Minimally Invasive Gynecologic surgery, Weston Florida. PATIENTS: A 52-year old woman with ADPKD with a large abdominal mass, abnormal uterine bleeding and symptomatic anemia. Imaging revealed a giant intramural cystic lesion of the uterus compressing the inferior vena cava. INTERVENTIONS: Uterine artery embolization and blood transfusion followed by a computed tomography guided cyst aspiration were performed on admission to alleviate anemia and abdominal pain and distension. Total laparoscopic hysterectomy with bilateral salpingectomy was performed in an outpatient setting. MAIN OUTCOME MEASURES: Management of large cystic degeneration of leiomyoma. RESULTS: Normal recovery from definitive surgery. Surgical pathology confirmed a benign, cystically dilated leiomyoma. CONCLUSION: This case demonstrates the management of giant intramural cyst lesion of the uterus using a minimally invasive surgical approach, as opposed to emergency surgery via laparotomy. CAPSULE: Large uterine leiomyoma with diffuse cystic degeneration in a patient with autosomal dominant polycystic kidney disease, in which step-wise treatments allows successful minimally invasive hysterectomy.

Dr. Andrew Huvos (1934-2006) retrospective: a tribute to the pathologist and the man.

Andrew G. Huvos was born in communist Budapest, Hungary, in March of 1934. At twenty-four he immigrated to New York City, working as a cytotechnologist at Delafield Hospital. Dr. Huvos attended the University of Gottingen Medical School in Germany, where he was awarded his MD degree. He completed a 1-year internship at New York Hospital, going on to Residency at Delafield Hospital and Fellowship at Presbyterian Hospital. Dr. Huvos ascended through the ranks to Attending Pathologist and Member at Memorial Hospital for Cancer and Allied diseases, at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City. Concurrently, he was appointed to Weill Medical College of Cornell University, where he was Professor of Pathology for over two decades. Dr. Huvos was an editorial referee for over half a dozen highly esteemed publications, including the New England Journal of Medicine and Cancer. He trained over a thousand oncological surgical pathology fellows, head and neck fellows, and surgeons. Dr. Huvos spent nearly 40 years at MSKCC and his career was accompanied by his authorship of 388 peer-reviewed publications and eighteen book chapters. His legacy leaves behind a generation of pathologists who have greatly benefited from his tutelage.

Poorly differentiated thyroid carcinoma presenting with gross extrathyroidal extension: 1986-2009 Memorial Sloan-Kettering Cancer Center experience.

PURPOSE: To describe the outcome of patients with poorly differentiated thyroid cancer (PDTC) presenting with gross extrathyroidal extension (ETE). MATERIALS AND METHODS: After obtaining Institutional Review Board approval, we performed a retrospective review of a consecutive series of thyroid cancer patients treated by primary surgical resection with or without adjuvant therapy at Memorial Sloan-Kettering Cancer Center from 1986 to 2009. Out of 91 PDTC patients, 27 (30%) had gross ETE (T4a), and they formed the basis of our study. Of 27 patients, 52% were women. The median age was 70 years (range 27-87 years). Ten patients (37%) presented with distant metastases; four to bone, three to lung, and three to both bone and lung. All patients had extended total thyroidectomy, except two who had subtotal thyroidectomy. Twenty patients (74%) had central compartment neck dissection and 11 also had lateral neck dissection. Four patients had pN0, six (30%) pN1a, and 10 (50%) pN1b neck disease. Twenty-one patients (77%) had adjuvant therapy: 15 (55%) radioactive iodine (RAI) only, three (11%) postoperative external beam radiation (EBRT) only, and three (11%) had both RAI and EBRT. Overall survival (OS), disease-specific survival (DSS), local recurrence-free survival (LRFS), and regional recurrence-free survival (RRFS) were calculated by the Kaplan Meier method. RESULTS: The median follow-up time was 57 months (range 1-197 months). The 5 year OS and DSS were 47% and 49%, respectively. This poor outcome was due to distant metastatic disease; 10 patients had distant metastases at presentation and a further six developed distant metastases during follow-up. Locoregional control was good with 5-year LRFS and RRFS of 70% and 62%, respectively. Overall, eight patients (30%) had recurrences: two had distant alone, two regional, two regional and distant, one local and distant, and one had local, regional, and distant recurrence. CONCLUSION: Aggressive surgery in patients with PDTC showing gross ETE resulted in satisfactory locoregional control. Due to the small proportion of patients who received EBRT (22%), it is not possible to analyze its benefit on locoregional control. Of significance is the observation that the majority of patients (60%) who presented with or subsequently developed distant metastases eventually died of distant disease. New systemic therapies to target distant metastatic disease are required for improvements in outcome.

Correlation of a priori DCE-MRI and (1)H-MRS data with molecular markers in neck nodal metastases: Initial analysis.

The aim of the present study is to correlate non-invasive, pretreatment biological imaging (dynamic contrast enhanced-MRI [DCE-MRI] and proton magnetic resonance spectroscopy [(1)H-MRS]) findings with specific molecular marker data in neck nodal metastases of head and neck squamous cell carcinoma (HNSCC) patients. Pretreatment DCE-MRI and (1)H-MRS were performed on neck nodal metastases of 12 patients who underwent surgery. Surgical specimens were analyzed with immunohistochemistry (IHC) assays for: Ki-67 (reflecting cellular proliferation), vascular endothelial growth factor (VEGF) (the "endogenous marker" of tumor vessel growth), carbonic anhydrase (CAIX), hypoxia inducible transcription factor (HIF-1α), and human papillomavirus (HPV). Additionally, necrosis was estimated based on H&E staining. The Spearman correlation was used to compare DCE-MRI, (1)H-MRS, and molecular marker data. A significant correlation was observed between DCE-MRI parameter std(k(ep)) and VEGF IHC expression level (rho=0.81, p=0.0001). Furthermore, IHC expression levels of Ki-67 inversely correlated with std(K(trans)) and std(v(e)) (rho=-0.71; p=0.004, and rho=-0.73; p=0.003, respectively). Other DCE-MRI, (1)H-MRS and IHC values did not show significant correlation. The results of this preliminary study indicate that the level of heterogeneity of perfusion in metastatic HNSCC seems positively correlated with angiogenesis, and inversely correlated with proliferation. These results are preliminary in nature and are indicative, and not definitive, trends portrayed in HNSCC patients with nodal disease. Future studies with larger patient populations need to be carried out to validate and clarify our preliminary findings.