Adebowale J. Adeniran

Yale University, New Haven, Connecticut, United States

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Publications (58)

  • [Show abstract] [Hide abstract] ABSTRACT: Significant racial disparities in survival for renal cell carcinoma (RCC) exist between white and black patients. Differences in access to care and comorbidities are possible contributors. To investigate if racial disparities persist when controlling for access to care, we analyzed data from a single-payer healthcare system. As part of a case-control study within the Kaiser Permanente Northern California system, pathologic and clinical records were obtained for RCC cases (2152 white, 293 black) diagnosed from 1998 to 2008. Patient demographics, comorbidities, tumor characteristics, and treatment status were compared. Overall survival and disease-specific survival (DSS) were calculated by the Kaplan-Meier method. A Cox proportion hazards model estimated the independent associations of race, comorbidity, and clinicopathologic variables with DSS. We found that compared to white patients, black patients were diagnosed at a younger age (median 62 vs. 66 years, P < 0.001), were more likely to have papillary RCC (15% vs. 5.2%, P < 0.001), and had similar rates of surgical treatment (78.8% vs. 77.9%, P = 0.764). On multivariate analysis, advanced American Joint Committee on Cancer (AJCC) stage, lack of surgical treatment, larger tumor size, and higher grade were predictors of worse DSS. Race was not an independent predictor of survival. Therefore, we conclude that within a single healthcare system, differences in characteristics of black and white patients with RCC persist; black patients had different comorbidities, were younger, and had decreased tumor stage. However, unlike other series, race was not an independent predictor of DSS, suggesting that survival differences in large registries may result from barriers to healthcare access and/or comorbidity rather than disease biology.
    Article · May 2016 · Cancer Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.
    Full-text Article · Feb 2016 · Proceedings of the National Academy of Sciences
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Poorly differentiated thyroid carcinoma, accounting for less than 10 % of all thyroid cancers, occupies an intermediate position between well-differentiated thyroid carcinoma and anaplastic thyroid carcinoma in regard to morphology and biologic behavior. The typical cytologic findings consist of predominantly small follicular cells with high nuclear-to-cytoplasmic ratio, marked nuclear crowding and overlapping, frequent mitotic figures, and irregular nuclei, frequently with evidence of necrosis. However, its differentiation from other thyroid neoplasms, in particular, follicular adenoma/carcinoma, and follicular variant of papillary thyroid carcinoma, may be difficult due to overlapping of cytologic features, such as microfollicular structures, irregular nuclei, and nuclear grooves. Therefore, when the cytologic findings do not permit a definitive diagnosis of poorly differentiated thyroid carcinoma, a diagnosis of “carcinoma of follicular origin” or “carcinoma not otherwise specified” should be rendered and not as “follicular variant of papillary thyroid carcinoma” and certainly not as “follicular neoplasm.”
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: The 2007 National Cancer Institute State of the Science Conference proposed a category of follicular lesion of undetermined significance (FLUS) or atypia of unknown significance (AUS) for lesions that are characterized by too great a degree of architectural or cytologic atypia for definitive assignment to the benign category but insufficient findings for a diagnosis of follicular neoplasm or suspicious for carcinoma. Studies have shown that routinely subclassifying lesions in the FLUS category into two help to better stratify these cases for management, and uniform criteria have been defined for both subcategories. The first subcategory is for cases that demonstrate low cellularity as well as a predominantly microfollicular pattern and no or minimal colloid. These features elicit concern for a follicular neoplasm. The second subcategory is used for cases that show nuclear atypia, which elicit concern for a papillary carcinoma.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Although architecturally, it fits into the category of follicular neoplasm, follicular variant of papillary thyroid carcinoma is classified as a subtype of papillary carcinoma because it behaves clinically like papillary carcinoma. The tumor is comprised predominantly of follicles; however, the characteristic nuclear features of classic papillary carcinoma are present. Papillary clusters are notably absent. The most common diagnostic dilemma is mistaking it for either goiter or follicular neoplasm. This is due to the fact that there is an overlapping diagnostic criteria for follicular lesions in general and also the paucity of diagnostic features of PTC in this variant, either because they are poorly developed or present only focally. When the predominant architecture is the presence of syncytial tissue fragments, especially in a background of colloid, the lesion can be misdiagnosed as nodular goiter.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Hyalinizing trabecular tumor of the thyroid gland is a rare neoplasm of follicular origin that is characterized by an encapsulated nodule, a prominent trabecular growth pattern, and stromal hyalinization. This tumor typically behaves in a benign fashion but malignant cases have been reported. Hyalinizing trabecular tumors are usually well circumscribed or encapsulated with variability in color. The possibility that hyalinizing trabecular tumor represents a variant of papillary thyroid carcinoma has been considered given that the tumors frequently coexist and they share similar morphologic and nuclear features. However, on genetic analysis, hyalinizing trabecular tumor has been shown to be a discrete entity from papillary thyroid carcinoma. Hyalinizing trabecular tumors are frequently mistaken for papillary thyroid carcinoma, medullary carcinoma, or paraganglioma, but immunohistochemical stains are helpful in resolving this.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: A common pitfall in the diagnosis of thyroid nodules is the inadvertent sampling of parathyroid tissue, which may be difficult to distinguish from thyroid tissue on FNA due to similar cytologic features. Parathyroid cells are usually loosely clustered into small groups, often with a syncytial arrangement forming branching, loose, two-dimensional clusters. Microfollicular architecture is prevalent on ThinPrep preparations and this may contribute to overinterpretation of parathyroid tissue as follicular neoplasm of the thyroid. Parathyroid cells on ThinPrep preparations show round, centrally placed nuclei with stippled nuclear chromatin. The nuclei often appear smaller and darker on ThinPrep preparations than on corresponding FNA smears. The cytoplasm is scant to moderate. In addition to pathologic features, clinical features and radiologic appearance of the lesion are also helpful to differentiate between thyroid and parathyroid tissue. When the diagnosis is in doubt, parathyroid hormone immunohistochemical stain should be performed and positive PTH stain will confirm parathyroid origin.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Chronic lymphocytic (Hashimoto) thyroiditis is an autoimmune disease that is characterized by the destruction of thyroid follicles by marked lymphoid infiltrate. The diagnosis is usually established by a combination of clinical features and serologic test results. One or more of a variety of circulating autoantibodies are identified in almost all patients, the most common of which are anti-thyroglobulin and antithyroid peroxidase. Intense and patchy infiltration of the gland by lymphocytes and plasma cells with formation of germinal centers is the most characteristic feature on histologic examination. Epithelial changes seen in Hashimoto thyroiditis include follicular atrophy and Hürthle cell metaplasia. Fine needle aspiration shows a cellular specimen that is characterized by a polymorphous population of lymphocytes. When there is a nonneoplastic Hürthle cell proliferation in Hashimoto thyroiditis, the cytologic picture resembles that of Hürthle cell neoplasm. In the florid lymphoid phase of Hashimoto thyroiditis, fine needle aspiration biopsy can yield an aspirate containing a dense population of lymphocytes that can be easily mistaken for malignant lymphoma.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Lymphocyte-only aspirates pose a significant diagnostic challenge in the interpretation of thyroid fine-needle aspiration specimens. Differential diagnosis includes Hashimoto thyroiditis, lymphoma, intrathyroidal lymph node, intrathyroidal thymoma, and thyroglossal duct cyst. Hashimoto thyroiditis especially in the florid lymphoid phase usually presents as lymphocyte-only aspirates. During this phase, numerous hyperplastic lymphoid follicles are seen throughout the gland, and they often replace the thyroid parenchyma. Lymphomas of the thyroid typically occur in older patients, almost always arise in a background of Hashimoto thyroiditis and are of B-cell lineage. Primary lymphomas of the thyroid gland are mainly diffuse large B-cell lymphoma (DLBCL) and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and to a much lesser extent Hodgkin and small lymphocytic lymphoma. Given the limitations of establishing a lymphoma diagnosis with only cytomorphology, morphological evaluation is commonly augmented with flow cytometry or immunohistochemistry in the diagnostic workup of lymphocyte-only fine-needle aspirates from the thyroid.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Among the pediatric and adolescent population, thyroid nodules are uncommon with an incidence of 1–2 % but with a much higher risk of malignancy (14–40 %), when compared to that of adult population. Recent studies have shown that FNA, rather than diagnostic lobectomy, should be the initial diagnostic tool of choice for managing thyroid nodule in the pediatric population. Based on TBSRTC, thyroid FNA demonstrated a sensitivity and specificity of 94 % and 81 %, respectively, for evaluating thyroid nodules in the pediatric population. The majority of the malignancies encountered in the pediatric population are papillary thyroid carcinoma. Although the authors did not observe an increase in the frequency of the diagnostic category FLUS/AUS, a higher frequency of FLUS/AUS (35 %) has been reported in the literature due partly to the reluctance to diagnose malignancy in a young patient and partly to the low cellularity secondary to difficulty in sampling of these lesions. The use of molecular testing for equivocal thyroid FNA in pediatric population has not been extensively investigated.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Recent advances have led to a better understating of the molecular pathways of thyroid carcinogenesis, in particular, papillary thyroid carcinoma, which is closely associated with the MAPK pathway. Various novel molecular diagnostic tests based on the detection of molecular biomarkers have been developed to improve the diagnostic accuracy of thyroid FNA with equivocal cytologic interpretations. The current commercially available molecular tools used in routine clinical setting are based on either the rule-out (gene expression classifier) or rule-in (somatic genetic mutations) approaches. New testing platforms, such as those based on next-gene sequencing or microRNAs, are continually being developed to offer more economical, streamlined, targeted, and accurate molecular diagnostic tools. Last but not least, it is important to recognize that molecular testing, like patient demographics and history, physical examination, thyroid ultrasound, hormonal assay, as well as FNA biopsy, is just one of many steps that can be undertaken in the evaluation of a thyroid nodule.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Cystic change is commonly seen in papillary thyroid carcinoma. Macrophages can be seen in variable numbers with or without hemosiderin-laden pigments. Some cytologic features have been found to be useful in the differential diagnosis between cystic papillary thyroid carcinoma and cystic degeneration in a benign goiter. Atypical histiocytoid cells have been described in smears of cystic papillary thyroid carcinoma. These atypical histiocytoid cells have abundant vacuolated cytoplasm, nuclear pleomorphism, and nucleoli. They are larger and more atypical than benign histiocytes. The combination of macrophages, hemosiderin, cellular debris, and old blood in the background may obscure distinction between cystic papillary thyroid carcinoma and cystic goiters. Ancillary immunohistochemical markers and mutational analysis may be useful in challenging specimens.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Secondary neoplasms of the thyroid gland are uncommon, but clinically they can be indistinguishable from primary thyroid tumors. The possibility of metastasis should always be considered whenever a patient presents with a thyroid nodule and they have a history of malignancy elsewhere in the body or when the cytologic picture is not consistent with or suggestive of common thyroid neoplasms. The most common primary sites of metastasis to the thyroid are kidney, lung, and breast, but the thyroid gland may also be involved by direct extension from malignancies of the head and neck region. It is important to distinguish secondary thyroid tumors from the primary tumors because patients who have metastasis to the thyroid have a poor prognosis in general, and most die shortly after the confirmation of distant metastasis. Immunohistochemistry is very helpful in the differential diagnosis.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: The finding of thyroid tissue in a neck mass without distinct connections to the thyroid gland is uncommon but poses a diagnostic dilemma to the cytologist as to whether the finding represents a metastatic thyroid malignancy to the cervical node or ectopic thyroid tissue/benign thyroid inclusions in cervical lymph node. Some consider that all thyroid tissues found in the lateral cervical nodes represent nodal metastases from a primary thyroid carcinoma while others believe the existence of benign thyroid tissue inclusions in cervical lymph nodes. The finding of cytologically benign-appearing follicular cells with or without colloid does not necessarily imply a benign process since the pattern of growth of certain thyroid carcinomas can be so well differentiated as to simulate non-neoplastic thyroid tissue. On the other hand, the presence of cytologic and/or architectural atypia in follicular cells, even if accompanied by a lymphoid background, does not always indicate a metastatic thyroid carcinoma. Therefore, it is best to adopt a conservative stance with respect to a diagnosis of malignancy as long as definitive cytologic features of papillary thyroid carcinoma are not identified.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Graves’ disease, an autoimmune disorder characterized by hyperthyroidism and a diffuse toxic goiter, is often treated by radioactive iodine 131I. Up to 35 % of patients with Graves’ disease, especially those with post 131I therapy, are found to have thyroid nodules which are often evaluated by fine-needle aspiration biopsy. Treatment with radioactive iodine can induce nuclear and cytoplasmic changes in follicular cells that could be mistaken as malignancy. The knowledge of a clinical history of Graves’ disease treated with 131I is of paramount importance in minimizing overdiagnosis of malignancy. On the other hand, patients with Graves’ disease can harbor thyroid malignancy, particularly, papillary thyroid carcinoma more than is seen in the general population. It is crucial to adhere strictly to the cytologic criteria in order to minimize over- and underdiagnosis of papillary thyroid carcinoma in patients with treated Graves’ disease.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Medullary carcinoma comprises 5–10 % of all thyroid malignancies, and it arises from the calcitonin-producing parafollicular C cells. Clinically, it occurs in two forms—familial and sporadic. Medullary carcinoma demonstrates variable behavior from indolent disease to highly aggressive, progressive disease. The main secretory product of the C cells is the hormone calcitonin, which serves as a useful sensitive marker for the presence of medullary carcinoma. There is a broad spectrum of cytopathologic features in medullary carcinoma. The aspirates are usually highly cellular; however, scant cellularity is encountered with carcinomas containing extensive amyloid deposits and calcification. Tumor cells are predominantly single cells, but can also be seen as sheets, loose clusters, syncytia, rosettes, cords, and papillae. The cells are usually uniform in size and shape but occasionally can present as large pleomorphic cells. Cytoplasm is moderate to abundant and finely granular. Nuclei are eccentrically placed, giving the cells a plasmacytoid appearance, and binucleation and multinucleation are common. Nuclei have a coarsely granular chromatin texture and inconspicuous nucleoli, thereby giving the so-called “salt and pepper” appearance. Intranuclear inclusions may be found in up to half of cases. Because of its diverse cytologic presentations with different cellular morphologies, medullary carcinoma can simulate other neoplastic processes including Hürthle cell neoplasm, anaplastic carcinoma, malignant lymphoma, carcinoid tumor, plasmacytoma, malignant melanoma, and soft tissue neoplasms. In difficult cases, immunocytochemistry with calcitonin, CEA, and thyroglobulin will solve the diagnostic dilemma.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Involvement of cervical lymph nodes by metastatic disease is reported in 20–50 % of patients with well-differentiated thyroid cancer. Fine-needle aspiration biopsy (FNA) is usually required to confirm or rule out metastasis because reactive lymphadenopathy is common in the neck region. Because of a small but substantial percentage of false-negative cases, thyroglobulin (Tg) assay of aspirate from cervical lymph nodes has been advocated to supplement FNA of suspicious lymph node in patients with proven or suspected differentiated thyroid cancer. A high sensitivity (95 %) and specificity (95 %) in the detection of nodal metastases from differentiated thyroid carcinoma have been reported with Tg assay. However, Tg assay of FNA should not replace cytologic evaluation because of the potential of both false-positive and negative results. In addition, standardization in terms of sample collection and analysis is still lacking.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Total thyroidectomy followed by surveillance of the neck and thyroid bed for recurrent disease is the mainstay of treatment for primary differentiated thyroid cancers. Ultrasound-guided fine needle aspiration (FNA) of the thyroid bed determines if the new lesion is recurrent thyroid cancer or residual hyperplastic thyroid tissue. The features of cytologic features of malignancy are usually similar to that in the primary tumor. Direct extension from head and neck squamous cell carcinoma as well as metastasis from a distant site can mimic thyroid bed recurrence of thyroid cancer. Benign entities may include hyperplasia of residual normal thyroid, normal parathyroid gland, benign lymph nodes, and benign reparative changes such as fibrosis and suture granulomas.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Hurthle cell changes are frequently seen in reactive/hyperplastic conditions and can be extensive, resulting in the formation of nodules that must be distinguished from their neoplastic counterparts, Hurthle cell adenomas and Hurthle cell carcinoma. The primary goal of thyroid FNA in the management of Hurthle cell nodules is to separate those for which surgery is indicated, i.e., Hurthle cell adenomas and carcinomas, from those that can be managed conservatively, i.e., adenomatous nodules with oncocytic changes and Hashimoto’s thyroiditis. The distinction between Hurthle cell adenomas and carcinomas is not possible on cytology because of the inability of cytology to establish the presence of capsular and/or vascular invasion. Therefore, rendering a diagnosis of Hurthle cell neoplasm implies that these lesions should be excised to exclude a malignancy. The criteria for diagnosing “follicular neoplasm, Hurthle cell type,” or “suspicious for a follicular neoplasm, Hurthle cell type” are moderately to markedly cellular aspirate that consists exclusively or predominantly (>75 %) of Hurthle cells with little or no colloid and lack of background lymphocytes. The Hurthle cells can be either small with high N/C ratio (≥50 %) (small cell dysplasia) or large with at least 2× variability in nuclear size (large cell dysplasia). The differential diagnosis includes other neoplasms such as oncocytic and tall cell variants of papillary thyroid carcinoma, medullary carcinoma, parathyroid adenoma, and metastatic renal cell carcinoma.
    Chapter · Jan 2016
  • Adebowale J. Adeniran · David Chhieng
    [Show abstract] [Hide abstract] ABSTRACT: Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70 % of thyroid malignancies. The most common variants are the conventional type. However, many other uncommon variants have been described; the classification of these variants is based on the architectural patterns, such as follicular, solid, and cribriform-morular variants; the cell types, such as oncocytic, tall cell, and columnar cell variants; and the stromal reaction such as diffuse sclerosing, Warthin-like, and those with nodular fasciitis-like stroma. The common denominator for all the variants is the presence of nuclear features of PTC. The cytology may not be representative of the major morphologic pattern because of sampling error. In addition, a definitive cytologic diagnosis of PTC can sometimes be challenging if the typical nuclear changes of PTC were subtle or not readily apparent. It is advantageous in recognizing certain variants, namely, those with more aggressive clinical course, preoperatively since it may help the clinicians to plan for more aggressive treatment.
    Chapter · Jan 2016