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Reactive Lymphadenopathies

The major question that confronts the surgical pathologist when examining a lymph node biopsy is whether the process is benign or malignant. The pathologist must be familiar with the histologic changes of a diverse group of non-neoplastic disorders to differentiate them from lymphoma, as well as to render a specific diagnosis or a differential diagnosis on morphologic grounds. A specific diagnosis often requires correlation with the…

Normal Lymphoid Organs and Tissues

Lymphoid tissues are the sites where precursor cells mature into immunocompetent lymphoid cells and where immune reactions to antigens occur. The lymphoid tissues and the stages of lymphocyte differentiation and maturation have an anatomy—they occur at specific sites in the body. They have an architecture—each lymphoid tissue is organized in a specific way, and cellular differentiation and reactions occur in specific sites within this organized tissue.…

Important Chromosomal Aberrations in Hematologic Neoplasms and Key Techniques to Diagnose Them

Types of Chromosomal Aberrations in Hematologic Malignancies Introduction to Human Chromosomes In 1888, Waldeyer was first to introduce the term chromosome (meaning “stainable body,” from the Greek chroma, meaning “color,” and soma, meaning “body”). Waldeyer referred to Walther Flemming, who coined the terms chromatin and mitosis in 1879 at Kiel University. Flemming was also first to describe germinal centers. Since the pioneering studies by Flemming and…

Molecular Diagnosis in Hematopathology

The understanding of the biologic basis of hematopoietic diseases in general and neoplasia in particular has been significantly enhanced by the application of molecular techniques to the study of these diseases. The use of Southern blotting hybridization analysis initiated the integration of molecular biologic techniques into hematopathology and has substantially contributed to understanding the clonality status of lymphoproliferative disorders. The availability of molecular probes to the…

Flow Cytometry

Flow cytometry (FCM) is invaluable in the diagnosis and classification of hematolymphoid neoplasms, and in determining prognosis and monitoring response to therapy. FCM is especially suited for immunophenotypic analysis of blood, fluids (e.g., cerebrospinal fluid [CSF], pleural fluid), and aspirations of bone marrow and lymphoid tissue. FCM is also ideal in small samples where its multiparametric nature allows the concurrent staining of cells with multiple antibodies…

Immunohistochemistry for the Hematopathology Laboratory

Perhaps in no other subspecialty of pathology does immunohistochemistry (IHC) play as important a role in the accurate diagnosis and definition of disease subtypes as it does in hematopathology. Before the development of this technology, the diagnosis of lymphoproliferative diseases depended on classification systems based solely on morphologic differences. The subjective use of morphologically based classification schemes led to difficulty in defining biologically different entities, and…

Collection, Processing, and Examination of Bone Marrow Specimens

Meaningful interpretation of a bone marrow specimen requires an adequate and well-prepared sample. The definition of adequacy depends on the clinical indication for the examination. For example, for staging lymphoma, a bilateral bone marrow core biopsy is superior to a unilateral biopsy ; thus, for this purpose, a bilateral biopsy defines adequacy. In contrast, for the diagnosis of acute leukemia, a unilateral bone marrow aspiration and…

Fine Needle Aspiration of Lymph Nodes

Fine needle aspiration (FNA) of superficial and deep-seated lymph nodes is a well-established and safe method for assessing lymphadenopathy in adult and pediatric patients. Patients with primary or recurrent lymphoma frequently undergo FNA, and this diagnostic modality is even more common in suspected reactive or metastatic lymphadenopathy. Using FNA as a first-line procedure has obvious benefits, such as rapid turnaround time, low cost, and low morbidity.…

Processing of the Lymph Node Biopsy Specimen

In recent years, technical strides in immunophenotyping and molecular genetic testing have revolutionized the diagnosis of hematolymphoid malignancies. Stained sections prepared from paraffin-embedded fixed tissues remain the foundation of histopathologic diagnosis. The accurate classification of lymphoid tumors and the subsequent clinical management of patients rely on the availability of adequate diagnostic tissue. A multiparameter approach to diagnosis is central to the World Health Organization (WHO) classification…

Diseases of the Paraganglia System

■ Paraganglioma Extra-adrenal paragangliomas arise from paraganglia distributed along the paravertebral sympathetic and parasympathetic chains and include tumors arising in the carotid body, jugulotympanic body, orbit, nasopharynx, larynx, vagal body, paraspinal chain (aorticosympathetic and visceral-autonomic), urinary bladder, and the organ of Zuckerkandl. Although the most common site of paraganglioma is within the adrenal gland (referred to as pheochromocytoma), this discussion will be limited to those arising…

Malignant Neoplasms of the Parathyroid Gland

■ Parathyroid Carcinoma Parathyroid carcinoma is a malignant neoplasm arising from the parathyroid parenchymal cells, comprising approximately 1% of all primary hyperparathyroidism (HPT) cases (no malignant adipose tumors are recognized in the parathyroid). Secondary parathyroid hyperplasia and neck irradiation are suggested as etiologic factors. There is also an increased incidence of carcinoma in patients with hereditary hyperparathyroidism–jaw tumor (HPT-JT) syndrome. There are no well-accepted histologic features…

Benign Neoplasms of the Parathyroid Gland

■ Parathyroid Adenoma A parathyroid gland adenoma is an encapsulated benign neoplasm of the parathyroid parenchymal cells (either chief or oncocytic cells). Parathyroid disease is separated into primary, secondary, or tertiary, based on whether the parathyroid gland is primarily the source of the disease or if the gland is reacting to exogenous stimulation, such as renal disease ( Chapter 26 ). This distinction is sometimes quite…

Non-Neoplastic Lesions of the Parathyroid Glands

■ General Considerations There are a variable number of glands (2 to 10), but usually four are present, symmetrically arranged within the upper and lower poles of the bilateral thyroid gland. Approximately 5% of people have more than four glands. The glands are usually soft, pliable, and measure < 0.5 cm (5 mm), with a combined weight of approximately 120 to 140 mg. It is agreed that no single…

Malignant Neoplasms of the Thyroid Gland

Thyroid gland malignancies account for about 3% of all cancers (13.5/100,000 population), while representing the most common malignancy of the endocrine system. In general, thyroid cancer afflicts young to middle-aged adults with environmental, genetic, and hormonal factors often playing an etiologic role. Iodine is essential for normal thyroid function and consequently, radioactive iodine can be used in treatment. Women are affected by thyroid diseases nearly four…

Benign Neoplasms of the Thyroid Gland

▪ Follicular Adenoma Follicular adenoma (FA) is a benign encapsulated neoplasm of follicular epithelial origin and is the most common neoplasm of the thyroid gland. Autopsy studies show that 3% to 5% of adult thyroid glands harbor an FA. A subset may represent a precursor lesion to follicular carcinoma. Clinical Features The most common tumor of the thyroid gland, FA is often discovered incidentally during routine…

Non-Neoplastic Lesions of the Thyroid Gland

■ Thyroglossal Duct Cyst The thyroglossal duct represents the tract in the midline neck through which the thyroid anlage descends during embryonic development. It begins at the foramen cecum at the base of the tongue, continues around the hyoid bone, and ends at the normal position of the thyroid gland in the pretracheal lower neck. Persistence of the thyroglossal duct postnatally can give rise to cysts…

Malignant Neoplasms of the Neck (Soft Tissue and Lymph Node)

■ Metastatic Squamous Cell Carcinoma Metastatic squamous cell carcinoma (SCC) in the neck often presents without a clinically apparent primary. The majority of cases of metastatic SCC to cervical lymph nodes are associated with high-risk human papillomavirus (HPV) from the oropharynx (base of tongue and tonsil), although conventional SCC from the upper aerodigestive tract is also common. The rich lymphatic plexus in the oropharynx can lead…

Benign Neoplasms of the Neck (Soft Tissue, Bone, and Lymph Node)

▪ Lymphangioma (Cystic Hygroma) Lymphangiomas are rare congenital lymphatic malformations, with up to 70% reported in the head and neck. They are separated into three types: capillary, cavernous, and cystic (cystic hygroma). Lymphangiomas comprise approximately 25% of all vascular neoplasms in children and adolescents; approximately 25% of cervical cysts are lymphangiomas. Clinical Features Lymphangioma (Cystic Hygroma)—Disease Fact Sheet Definition ▪ A benign cystic neoplasm composed of…

Non-Neoplastic Lesions of the Neck (Soft Tissue, Bone, and Lymph Node)

Non-neoplastic lesions of the neck can be broadly classified into developmental cystic anomalies; infections and related diseases/lesions; and reactive, inflammatory, and tumor-like lesions. ■ Branchial Cleft Anomalies Branchial cleft anomalies are divided according to the branchial apparatus involved and are further divided into cysts, sinuses, or fistulas. When the name branchial cyst is used without further qualifications, it generally refers to a cyst of second branchial…

Malignant Neoplasms of the Ear and Temporal Bone

■ Squamous Cell Carcinoma (External Auditory Canal and Middle Ear) Squamous cell carcinoma (SCC) is a malignant tumor of squamous keratinocytes. Ultraviolet (UV) radiation is considered etiologic for external ear lesions, whereas chronic inflammation (otitis media) may be associated with middle ear tumors. Clinical Features Squamous Cell Carcinoma (External & Middle Ear)—Disease Fact Sheet Definition ■ An invasive epithelial tumor with squamous differentiation (keratinocytes) Incidence and…