Gherardi: Fine-Needle Biopsy of Superficial and Deep Masses: Interventional Approach and Interpretation Methodology by Pattern Recognition






By definition, fine-needle biopsy (FNB) is a diagnostic procedure employing needles of small caliber that are inserted into superficial and deep-seated masses to collect, at each pass, a minimal amount of cellular sample from the lesion under investigation. The harvest is acquired with or without aspiration, and it is smeared onto a glass slide or processed for histological examination. In some cases, the use of larger-caliber and cutting needles may be required to provide a core of tissue whose histological evaluation can assist in the diagnostic process. Direct smears, cell blocks, and cores represent the diagnostic yield of FNB and they provide the pathologist with a potentially enormous amount of diagnostic information that in most cases is expected to lead, in experienced hands and in the proper context, to a reliable and tissue-equivalent diagnosis.
The field of application of FNB is the diagnosis of malignant tumors and their simulants. Nowadays, oncological treatment is becoming decreasingly destructive in surgical terms and increasingly aimed at pharmacological and patient-tailored therapies. Remarkable advances in our understanding of neoplastic progression at the cellular and molecular levels have also spurred the discovery of molecularly targeted drugs. Genomic profiling is increasingly able to allow the re-classification of cancers into new molecularly and prognostically homogeneous subgroups. In future scenarios–which already exist for some types of malignancies–the determination of molecular predictors of response will play a decisive role in defining the first line of therapy administered to the patient, with the goal of improving efficacy and maximizing the possibility of long-term control. Moreover, the discovery of molecularly targeted drugs has recently encouraged their use in patients with advanced stages of disease, with promising results.
What role for pathological diagnosis can be expected in these future scenarios? Obviously, the diagnosis of malignancy will continue to be the essential requisite for treatment and, at least for many years to come, it will be based on the consideration and proper evaluation of morphological findings. The major difference from the past, however, will be that the higher number of solid tumors amenable to first-line pharmacological therapy will result in a smaller number of tumor specimens available for pathological diagnosis, because surgical excision of the tumor will no longer represent the first event in the management of a patient with an early-stage tumor. In addition, in order to verify their possible candidacy for targeted therapies, patients presenting with advanced and inoperable disease will require a more precise and detailed tissue diagnosis than previously deemed necessary. In summary, pathologists will be faced with an ever decreasing amount of cellular material collected for tumor  diagnosis and for the determination of selected biomarkers that indicate the most appropriate therapeutic regimen.
Based on these considerations, FNB is likely to experience a renaissance in its utilization in the near future. FNB gained a considerable popularity in the 1980s in the USA and in Europe, as a consequence of a significant tumor burden in those populations and the correlative escalating financial costs for disease management. Despite the initial skepticism of the medical community, the recognition of the practical advantages of FNB and its cost effectiveness led to the development of a generation of pathologists who were confident in the interpretation of such minimal cellular samples and, no less importantly, in the sampling procedure. This was a short-lived event, as problems of different kinds eventually discouraged pathologist performed FNB. Instead, the trend reverted to the preference for incisional or excisional surgical biopsy for the diagnosis of many types of tumors. As a consequence, expertise in cytological sample interpretation and recruitment declined. Indeed, in several diverse clinical settings, pathologists eventually ignored their duty to provide the patient with the most reliable diagnosis, with the least patient discomfort, and at the lowest cost. Times are changing, however, and the need for reliable tissue-equivalent diagnosis as the first step in any decision regarding oncological treatment in patients presenting with early- or late-stage disease will soon become increasingly compelling in daily practice. Accordingly, pathologists must be prepared for these new developments.
The aim of this monograph is to testify to the applicability of FNB in these clinical settings, with the wider ambition of suggesting a relatively novel approach to tumor diagnosis. In fact, the conventional approach of many textbooks published so far concerning the practice of FNB has been to describe the cytopathological picture starting from the end, i.e., the lesion as it appears in histological preparations. This book offers the alternate approach of starting from the very beginning of the diagnostic work-up, i.e., a morphological evaluation of the specimen in the given case, and provides criteria to classify all observations according to a reliable and reproducible pattern-profiling approach. Pattern recognition is central to diagnostic reasoning in this field of pathology and assists the observer in identifying the list of possible diagnoses matching the detected profile. Once the major pattern has been identified, the diagnostic possibilities are dramatically reduced. In some cases, there will be an unequivocal correspondence between a given pattern and a disease entity, while in others multiple pathological entities can match the observed pattern profile. In the former situation, the predictive value of the morphological pattern per se is very high and a definite diagnosis can be released. In the latter situation, detecting the correct pattern helps one to identify a list of possible diagnostic alternatives, each expressed in probabilistic terms. In this context, the predictive value of the morphological pattern for a specific disease entity can be enhanced by properly considering pre-analytical data and/or by including additional findings obtained from ancillary techniques, thus reaching a sufficiently high predictive value. The addition of new data to pattern profiling brings order to a group of lesions whose least common denominator is a specific cytomorphological pattern. In summary, one can vastly simplify the cytopathological investigation and more critically express the real possibility that the given sample matches a specific diagnosis.
In the book, the classical cytology of breast carcinoma and its simulants, of thyroid nodular lesions, and of malignant lymphomas have been revisited under a patternprofiling approach, with the aim of introducing reproducibility as much as possible in this field of pathology, which is still dominated by subjectivity. Moreover, a common pattern-recognition approach is described for most tumors and pseudotumors encountered in abdominal and intrathoracic sites, with the hope that it represents a useful key to interpret all possible morphological findings. A decision tree is subsequently described such that, when possible, a conclusive diagnosis can be reached. Last but not least in importance is an initial chapter in which some of the basic modalities of what I call “interventional cytology” and the most useful procedures for sample triage are reviewed. Central to the book is the belief that the pathologist, who is not a niche expert but rather a complete physician with distinguished wide-ranging abilities, should be involved not only in interpreting the cellular harvest but to an equal extent also in the sampling procedure and in the pre-analytical evaluation of the patient.

Contents
1 Methods

1.1 Sampling
1.1.1 The Interventional Pathologist
1.1.2 Preanalyitical Evaluation and Requirements
1.1.3 Needles
1.1.4 Aspiration vs.Non-Aspiration Technique
1.1.5 Core-Needle Biopsy Devices
1.1.6 Sampling Procedures
1.2 Specimen Triage
1.2.1 Direct Smears and Smearing Techniques
1.2.2 Fixation
1.2.3 Cytospin Preparation
1.2.4 Cell-Block Prepark ation
1.2.5 Direct Smear vs. Cell-Block Preparation for Immunohistochemistry
1.2.6 Staining Methods
1.3 Microscopic Evaluation
1.3.1 Pattern Recognition Approach
1.3.2 Diagnostic Accuracy
2 Breast
2.1 Introduction
2.2 Non-Operative Diagnosis of Breast Cancer
2.3 Fine-Needle vs. Core-Needle Sampling
2.4 Diagnostic Terminology
2.5 Diagnostic Approach
2.6 Basic Principles of Cytological Evaluation
2.6.1 Background
2.6.2 Cellularity
2.6.3 Aggregation Patterns of Epithelial Glandular Cells
2.6.4 Cellular Dissociation
2.6.5 Ancillary Elements
2.6.6 Fine Cytomorphological Features of Epithelial Glandular Cells
2.7 Primary Diagnosis of Common Benign or Premalignant Breast Lesions
2.7.1 Benign Fibroepithelial Lesions
2.7.2 Sclerosing Lesions Following Fat Necrosis
2.7.3 Intramammary Lymph Nodes
2.7.4 Proliferative Breast Lesions
2.8 Diagnosis of Carcinoma
2.8.1 Specimen with Adequate Cellularity
2.8.2 Samples with Minimal to Low Cellularity
2.8.3 Limitations and Pitfalls
2.9 Variants of Carcinoma
2.9.1 Mucinous Carcinoma
2.9.2 Tubular Carcinoma
2.9.3 Medullary Carcinoma
2.9.4 Triple-Negative “Basal-Like” Carcinoma
2.9.5 Micropapillary Carcinoma
2.9.6 Carcinoma with Apocrine-Type Differentiation
2.9.7 Adenoid Cystic Carcinoma
2.9.8 Metaplastic Spindle Cell Carcinoma
2.10 Differential Diagnosis and Possible Misdiagnoses
2.10.1 Fibroepithelial Lesions
2.10.2 Intraductal/Intracystic Papilloma
2.10.3 Mucocele-Like Lesions
2.10.4 Retroareolar Abscess
2.10.5 Hypercellular Sample in the Elderly
2.10.6 Complex Sclerosing Lesion/Radial Scar
2.10.7 Angiosarcoma After Breast-Conserving Therapy
3 Thyroid
3.1 Introduction
3.2 Indications for FNB
3.2.1 Palpable Nodule
3.2.2 Non-Palpable Nodule Discovered via Imaging
3.3. FNB Sampling Technique
3.4 The Cold Nodule: Histopathological Findings and Clinicopathological Correlates
3.4.1 Nodular Hyperplasia
3.4.2 Follicular Adenoma
3.4.3 Hyaline Trabecular Adenoma
3.4.4 Thyroiditis
3.4.5 Papillary Carcinoma
3.4.6 Follicular Carcinoma
3.4.7 Medullary Carcinoma
3.4.8 Poorly Differentiated Follicular (“Insular”) Carcinoma
3.4.9 Poorly Differentiated Carcinomas with Papillary, Hürthle Cell, or Medullary Carcinoma Cell Features
3.4.10 Undifferentiated (Anaplastic) Carcinoma
3.4.11 Intrathyroid Parathyroid Tumors
3.5 Immunohistochemistry of Thyrf oid Lesions
3.6 Analytical Approach to the Cytological Sample
3.6.1 Background
3.6.2 Proper Thyroid Cell Types
3.6.3 Specimen Adequacy
3.7 Towards a Uniform Diagnostic Terminology: The National Cancer Institute (NCI) Classification Scheme, 2008
3.8 Pattern Profiling of FNB Samples
3.8.1 Benign and Non-Neoplastic Follicular Lesions
3.8.2 Potentially Neoplastic Lesions
3.8.3 Malignant Lesions
4 Lymph Nodes:Diagnosis of Malignant Lymphoma
4.1 Introduction
4.2 Histological vs. Cytological Approach to Lymphoid Lesions
4.3 Indications for Fine-Needle Biopsy of Lymph Nodes
4.4 Evaluation of the Cellular Sample
4.4.1 Cellularity
4.4.2 Lymphoglandular Bodies
4.4.3 Identification of Cell Type
4.5 Pattern Profiling of FNB Samples
4.5.1 Polymorphous Small- and Large-Cell Pattern, Tingible-Body Histiocytes Present
4.5.2 Polymorphous Small- and Large-Cell Pattern, Tingible-Body Histiocytes Absent
4.5.3 Polymorphous Cell Pattern, Large Cells Prevalent
4.5.4 Polymorphous Cell Pattern, Small Cells Prevalent, with Scattered Large Atypical Blasts
4.5.5 Monomorphic, Small Lymphoid Cell Pattern
4.5.6 Pleomorphic, Small- and/or Large-Cell Pattern
4.6 Concluding Remarks
5 Cytological Pattern Profiling of Tumors fromDifferent Visceral Sites
5.1 Preliminary Remarks
5.2 Glandular-Cell Morphology
5.2.1 Tubulo-Acinar Pattern
5.2.2 Tubulo-Papillary Pattern
5.2.3 Mucinous Pattern
5.2.4 Solid, Three-Dimensional (Structureless) Pattern
5.2.5 Non-Cohesive Cell Pattern
5.2.6 Immunohistochemical Identification of the Primary Tumor Site
5.3 Squamous or Squamoid Cell Morphology
5.3.1 Keratinizing Pattern
5.3.2 Non-Keratinizing Pattern
5.4 Basaloid-Cell Morphology
5.4.1 Basaloid Squamous Cell Carcinoma Pattern
5.4.2 Adenoid Cystic Carcinoma Pattern
5.5. Transitional-Cell Morphology
5.6 Small-Cell Morphology
5.6.1 Monomorphous Cell Pattern with Tendency to Aggregation and Mild Nuclear Atypia
5.6.2 Pleomorphic Cell Pattern with Tendency to Aggregation and Marked Nuclear Atypia
5.6.3 Pleomorphic Cell Pattern with Marked Cellular Dissociation
5.7 Large-Cell Morphology
5.7.1 Monophasic Pattern
5.7.2 Biphasic Pattern
5.8 Clear-Cell Morphology
5.8.1 Immunohistochemistry of Clear-Cell Tumors
5.9 Oxyphil/Oncocytic- or Oncocytoid- Cell Morphology
5.10 Epithelioid- and Spindle-Cell Morphology
6 Abdomen
6.1 Focal Liver Lesions
6.1.1 Hepatocellular Carcinoma
6.1.2 Cholangiocarcinoma
6.1.3 Carcinoma of the Gallbladder Involving the Liver
6.2 Pancreatic Tumors
6.2.1 Ductal Adenocarcinoma
6.2.2 Acinar Cell Carcinoma
6.2.3 Mucinous Cystic Neoplasms
6.2.4 Serous Cystic Neoplasms
6.2.5 Tumors of the Endocrine Pancreas
6.2.6 Undifferentiated and Spindle Cell Carcinoma
6.3 Renal Tumors
6.3.1 Clear-Cell Carcinoma
6.3.2 Papillary Carcinoma
6.3.3 Chromophobe-Cell Carcinoma
6.3.4 Collecting-Duct (Bellini’s) Adenocarcinoma
6.3.5 Oncocytoma
6.3.6 Angiomyolipoma
6.3.7 Special Problems in the Differential Diagnosis of Renal Tumors
6.4 Adrenal Gland Tumors
6.4.1 Adenoma of the Adrenal Cortex
6.4.2 Carcinoma of the Adrenal Cortex
6.4.3 Pheochromocytoma
6.4.4 Metastatic Malignancies
6.5 Ovarian Tumors
6.5.1 Serous Tumors
6.5.2 Mucinous Tumors
6.5.3 Endometrioid Carcinoma
6.5.4 Clear-Cell Carcinoma
6.5.5 Mixed Mesodermal Tumors
6.5.6 Transitional Cell Tumors
6.5.7 Granulosa Cell Tumor
6.5.8 Undifferentiated Small-Cell Carcinoma
6.5.9 Dysgerminoma
6.5.10 Squamous Cell Carcinoma Arising in Mature Teratoma
6.5.11 Metastatic Malignancies
6.6 Tumors Growing into the Peritoneal Cavity
6.6.1 Gastrointestinal Stromal Tumors
6.6.2 Intra-Abdominal (Mesenteric) Fibromatosis
6.6.3 Peritoneal Lesions
6.7 Tumors of the Abdominal Wall
6.8 Tumors of the Retroperitoneal Space
6.8.1 Malignant Lymphomas
6.8.2 Soft-Tissue Tumors
6.8.3 Germ Cell Tumors
7 Lung, Mediastinum, and Pleura
7.1 Introduction
7.1.1 Indications for FNB
7.1.2 Contraindications and Complications
7.1.3 Diagnostic Accuracy
7.1.4 Technical Considerations
7.2 Lung
7.2.1 Classification and Clinical Presentation of Pulmonary Epithelial Malignancies
7.2.2 Adenocarcinoma
7.2.3 Adenosquamous Carcinoma
7.2.4 Squamous Cell Carcinoma
7.2.5 Large-Cell Carcinoma
7.2.6 Basaloid Cell Carcinoma
7.2.7 Spindle Cell Carcinoma
7.2.8 Pleomorphic Carcinoma
7.2.9 Neuroendocrine Tumors
7.2.10 Pulmonary Metastatic Malignancies
7.2.11 Benign Lesions
7.2.12 Rare Tumors
7.3 Mediastinum
7.3.1 Tumors of the Thymus
7.3.2 Germ-Cell Tumors
7.4 Pleura and Chest Wall
7.4.1 Malignant Mesothelioma
7.4.2 Solitary Fibrous Tumor
Subject Index

Book Details

  • Paperback: 228 pages
  • Publisher: Springer; 1 edition (September 18, 2009)
  • Language: English
  • ISBN-10: 9788847014329
  • ISBN-13: 978-8847014329
  • ASIN: 8847014328
  • Product Dimensions: 10.2 x 7.6 x 0.5 inches
List Price: $129.00
 

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