Lymph Node FNC

Cytopathology of Lymph Nodes and Extranodal Lymphoproliferative Processes

P. Zeppa, I. Cozzolino, P., Zeppa, I., Cozzolino, Philippe Vielh, Philippe, Vielh

• Publisher: S. Karger
• Year: 2017
• Print ISBN: 9783318061147
• eBook ISBN: 9783318061154
• Topic: Medicine
• Subtopic: Hematology

This well-illustrated monograph presents a comprehensive description of Fine-Needle Cytology (FNC), including technical procedures and ancillary techniques, applied to the lymph node (LN). Possibilities and limitations are highlighted to produce accurate cytological diagnosis of LN and cytological criteria, and to be exploited for extra-nodal lymphoproliferative processes. The normal LN structure and corresponding cytological patterns are described. Cytological, phenotypical, and molecular features are reviewed along with diagnostic criteria for various medical conditions such as lymphadenitis and lymphadenopathies, Hodgkin and Non-Hodgkin lymphoma, pediatric lymphoadenopaties, immunodeficiency-associated lymphoproliferative disorders, extra-nodal lymphoproliferative processes, metastases, and other non-lymphomatous processes. LN-FNC requires knowledge of hemathopathology and imaging techniques, as well as dexterity with FNC performing, smearing, and material management. Rapid on-site evaluation (ROSE), the choice of ancillary techniques and molecular procedures case by case are required to produce accurate and comprehensive diagnosis. This book will help cytopathologists to conduct these tasks in various organs and clinical contexts. LN-FNC requires knowledge of hemathopathology and imaging techniques, as well as dexterity with FNC performing, smearing, and material management. Rapid on-site evaluation (ROSE), the choice of ancillary techniques and molecular procedures case by case are required to produce accurate and comprehensive diagnosis. This book will help cytopathologists to conduct these tasks in various organs and clinical contexts.

Chapter 6

Zeppa P, Cozzolino I: Lymph Node FNC. Cytopathology of Lymph Nodes and Extranodal Lymphoproliferative Processes.
Monogr Clin Cytol. Basel, Karger, 2018, vol 23, pp 60–76 (DOI: 10.1159/000478882)

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Paediatric Lymphadenopathies

Lymphadenopathies frequently occur in children. Roughly half of children in good health have palpable lymph nodes (LNs), and relevant LN enlargements (LNe) may occur after mild infections and even without a relevant clinical background [1–6]. Reactive LNe account for approximately 75% of paediatric and 25% of adult lymphadenopathies; therefore, the clinical relevance of LNe in children is different compared to adults [3]. Nonetheless, the persistence of LNe in children may worry parents and paediatricians; therefore, enlarged LN are often removed and, in most cases, histology reveals reactive unspecific processes. As in the case of adults, fine-needle cytology (FNC) can diagnose most paediatric lymphadenopathies, provided that the cytopathologists are informed of the clinical data, perform the FNC and rapid on-site evaluation (ROSE) personally, and are aware of the specificities of paediatric pathology.

Clinical Data

LNs larger than 2 cm in children are considered abnormal. Acute lymphadenopathies are generally caused by known or unknown bacterial or viral processes, and should shrink in less than 2 weeks. Subacute or chronic LNe lasting longer than this are most likely caused by chronic infections or malignant processes. Clinical information is mandatory for an accurate LN-FNC, including the pain or tenderness of LNe, fever, malaise, sore throat, upper respiratory tract infections, toothache, ear pain, insect bites or exposure to animals, exposure to mycobacteria and other infectious agents, vaccinations (smallpox, MMR, diphtheritis, poliomyelitis, typhoid fever) or drug consumption (phenytoin, pyrimethamine, phenylbutazone, isoniazide). All these factors, including storage diseases, may be associated with single or multiple, mild or relevant LNe. The evaluation of the LNe drained area is also important because LNe may be caused by specific pathological processes of corresponding areas, like conjunctivitis or dermatitis [1–6].

Laboratory Evaluation

Neutrophilic leucocytosis is generally associated with bacterial infections and lymphocytic leucocytosis with Epstein-Barr virus (EBV) and other viral infections. Lymphocytic leucocytosis with blasts is indicative of leukaemia; leucopenia, low levels of haemoglobin and platelets may be indicative of neoplastic bone marrow involvement. Lymphopenia with T cell impairment may occur in HIV infections, congenital immunodeficiency disorders, or post-transplantation immunodeficiency. The erythrocyte sedimentation and C-reactive protein levels are evaluated as inflammation and infection indicators, and may help in assessing the patient’s response to treatment. High serum levels of lactate dehydrogenase and uric acid are expressions of rapid cell turnover, and are often associated with malignancy. Specific serological data are required in cases of EBV, HIV, cytomegalovirus (CMV), and parvovirus infections. PCR or purified protein derivative (PPD) tests, interferon-gamma release assays, and the tuberculin skin test may be used in cases of mycobacterial infection.

Table 1. LNe stations and paediatric reactive and neoplastic processes

	Primary pathologies
Localized LNe Cervical	Reactive: mononucleosis, herpes virus, coxsackievirus, cytomegalovirus, HIV, Staphylococcus aureus, Streptococcus pyogenes (group A), mycobacteria, cat-scratch disease Neoplastic: HL, NHL, PTC PSRCT
Submandibular	Reactive: dental abscess, atypical mycobacteria, sarcoidosis, KD, RDD Neoplastic: HL, NHL PSRCT
Supraclavicular	Reactive: mycobacteria, fungi Neoplastic: HL, NHL, PTC, thoracic/abdominal PSRCT, germinal tumours
Axillary	Reactive: staphylococcal and streptococcal skin infections, cat-scratch disease, sarcoidosis Neoplastic: NHL, leukaemia
Inguinal	Reactive: unspecific, skin pathologies Neoplastic: NHL, PSRCT, germinal tumour
Generalized LNe Infections	Mononucleosis, HIV, miliary tuberculosis, typhoid fever
Malignancies	NHL, leukaemia
Autoimmune	Systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis
Drugs	Phenytoin, pyrimethamine, phenylbutazone, iso
Vaccines	Smallpox, MMR, diphtheritis, poliomyelitis, typhoid fever
Storage diseases	Gaucher, Niemann-Pick diseases
Others	Haemophagocytic lymphohistiocytosis, Langerhans cell hysticytosis
HL, Hodgkin lymphoma; NHL, non-Hodgkin lymphoma; PTC, papillary thyroid carcinoma; PSRCT, paediatric small round-cell tumours; KD, Kikuchi disease; RDD, Rosai-Dorfman disease.

Primary Pathological Processes and Lymph Node Stations

Whereas there is not a mandatory correlation between the LNe stations and specific pathological processes, the site of LNe is often relevant. Cervical LNe occur in reactive and neoplastic processes; upper anterior cervical LNe are mainly associated with upper respiratory infections or lymphomatous and non-lymphomatous neoplastic processes. Lower anterior cervical LNe are frequently involved in papillary thyroid carcinoma, while cervical posterior LNe are more frequently associated with skin infections or toxoplasmosis. Axillary or epitrochlear LNe may occur in Bartonella infections (cat-scratch disease) and preauricular LNe may appear in keratoconjunctivitis. Supraclavicular LNe usually have a high rate of malignancy (Hodgkin lymphoma [HL], metastases). Inguinal LNe are mostly reactive, but may be involved in tumoral lymphomatous and non-lymphomatous processes as well (Table 1).

Ultrasonography

Ultrasonography (US) is the first non-invasive procedure in for LNe evaluation. Basic information firstly concerns the LN nature of a clinically observed nodule and differential diagnosis with other nodules or swellings that may simulate an LNe (Table 2). The number of LNe (single or a group), exact size, shape, borders, diameters ratio, presence and shape of the hilum, expansion of compartments (cortex-paracortex or medulla), echogenicity, and the vascular pattern at power Doppler are precious information for cytopathologists. Experienced radiologists may orientate the LNe basic diagnosis, such as reactive, suppurative, or neoplastic enlargement, and may even suggest specific entities. US assists FNC by directing the needle in the LNe and in specific selected areas [7].

Table 2. Pathological entities clinically simulating paediatric LNe

Technical Procedures

FNC, ROSE, and the management of obtained material are similar for children and adults [see Chapter 2, this vol., pp. 14–18], while the clinical approach is different. During the FNC, children under the age of 3 years might be immobilized by a parent to reduce the stress for both the child and the parents. Children older than 7–8 years may overcome the natural fear of FNC and collaborate with the help of reassuring explanations. The most difficult paediatric patients, in the authors’ experience, are those aged in the middle: too big to be immobilized and too young to collaborate, whereas young patients sometimes appear to be wiser and more collaborative than parents. In any case, cytopathologists should be aware that multiple passes, easily performed in adults, are difficult to obtain in children, and an accurate management of diagnostic material is mandatory.

Nodules and Swellings Simulating LNs

As in adults, some paediatric nodules and swellings may clinically simulate LNe. For example, branchial cyst, thyroglossal duct cyst, thyroid nodule, sternocleidomastoid fibroma, epidermoid cyst, and even cervical rib may be clinically suspected as LNe, and correctly diagnosed by FNC (Table 2). Branchial cysts may appear as a recurrent swelling or nodule of the anterior cervical or the lower sternocleidomastoid area. FNC generally shows a suppurative background, where a variable number of squamous cells reveal the non-LN nature. Thyroglossal duct cyst is generally placed in the middle of the tongue, and often moves with tongue protrusion and swallowing. Inflammatory or colloid cells may be observed at FNC. Thyroidal nodules are identified by colloid and follicular cells, while sternocleido-mastoid fibroma may show scanty spindle cells. FNC of an epidermoid cyst generally produces necrotic, bad-smelling materi...

Table of contents

• Cover Page
• Front Matter
• Historical Background, Clinical Applications, Controversies
• Fine-Needle Cytology: Technical Procedures and Ancillary Techniques
• Lymph Nodal Structure and Cytological Patterns
• Lymphadenitis and Lymphadenopathy
• Non-Hodgkin Lymphoma
• Hodgkin Lymphoma
• Paediatric Lymphadenopathies
• Immunodeficiency-Associated Lymphoproliferative Disorders
• Extranodal Lymphoproliferative Processes
• Metastases
• Lymph Node Haematopoietic, Histiocytic, Dendritic Proliferations and Other Lymphoid Organs
• Subject Index
• Back Cover Page