This is the original standard operation of cervical lymphadenectomy to which all the other modifications have been applied. It entails removal of ipsilateral nodal groups extending from the lower border of the mandible superiorly to the clavicle inferiorly and from the lateral border of sternohyoid muscle, hyoid bone, and contralateral anterior belly of digastric muscle medially to the anterior border of trapezius muscle laterally. Thus, nodal groups of level I–V are removed, while the anterior compartment (central, level VI), suboccipital, peri-parotid (except for the infra-parotid LNs lying in the submandibular triangle), retropharyngeal, and buccinators LNs are not. It also includes the removal of spinal accessory nerve (SAN), IJV, and SCM.

This entails the removal of the same nodal groups as described in RND while preserving one or more of the non-lymphatic structures (SAN, IJV, and SCM). According to the current terminology, the preserved non-lymphatic structure should be named in the operation title, e.g., modified RND with preservation of IJV and SAN.

This refers to the cervical lymphadenectomy with preservation of one or more nodal groups included in the original RND. This approach is based on the predictable patterns of nodal metastasis according to the site of the primary malignancy. As a result, different variations of lymphadenectomy have been described including:

To obtain a unified terminology as regards to the variations in the extent of excision, it is recommended to mention the levels and sublevels excised following the term SND, e.g., SND [level VI].

This entails removal of additional LN groups (including retropharyngeal, superior mediastinal, paratracheal, or buccinator LNs) or non-lymphatic structures or both, which are not included in the standard RND operation. Examples of non-lymphatic structures that can be removed include the vagus nerve, hypoglossal nerve, carotid artery, paraspinal muscles, or the overlying skin. The additional removed structures should be mentioned in the operation title.

Cervical lymphadenopathy may be classified according to its etiology into malignant, infectious, autoimmune, miscellaneous, and iatrogenic (due to medications). These broad categories can be easily remembered using the mnemonic MIAMI [14].

In General, CLA may be due to lymphoid hyperplasia or infiltration [15].

Cervical lymphadenopathy may occur when the draining nodes react to a nearby infection in the head and neck region including upper respiratory infection or when the infectious agent localizes in the node itself.

Although CLA is more commonly caused by a benign etiology, a sinister underlying malignant process is not uncommon, necessitating careful evaluation of such patients. Exclusion of malignancy is in fact the first and the single most important aim sought by the physician when evaluating CLA. The incidence of malignancy in patients with CLA seems to vary considerably with their demographics: age, gender, and race. The rate of malignant etiologies rises with age. A cross-sectional study by Biswas et al. [19] demonstrated that the rate of malignancy among patients with CLA was 12.1 %, 21.7 %, and 100 % in the age groups <14, 15–59, and ≥60 years, respectively. In their study, Shakya et al. [34] observed a malignancy rate as high as 50 % in patients with CLA in 51–60-year age group. Such high incidence of malignancy among the aforementioned age groups led to the belief that any neck mass in an adult should be suspected as malignant until proven otherwise [35]. Gender issue has also been studied with the uniform finding of higher frequency of malignancy among males [36]. Similarly, incidence of malignancy in patients with CLA differs among different racial groups. A malignancy rate as high as 50 % was observed among Iranians presenting with unknown neck masses [37], while it was 28.2 % and 4.8 % among Indians and Nepalese, respectively [19, 34].

Malignant cervical LNs may be caused by secondary metastasis from another primary or less commonly by lymphoma [19, 34]. However, in their audit of 140 patients with CLA, Magsi et al. [38] found that lymphoma was more common than metastasis. Among the latter group, Naeimi et al. [37] found that SCC was the most common pathology regardless of age with the larynx and hypopharynx being the most common sites of the primary tumor. Similar findings were reported by Biswas et al. [19] with adenocarcinoma coming second in frequency. Lymphoma, as a cause of malignant CLA, ranks the second in frequency with NHL being more common in some series [19], while others reported that Hodgkin’s lymphoma was more common [37].

Histologically, the presence of Reed-Stenberg cells (large cells with abundant basophilic cytoplasm and multiple nuclei) in a background of inflammatory cells is characteristic of Hodgkin’s disease (HD) (Fig. 8.6). The WHO classified HD into five subtypes according to the predominant cell types: (1) nodular sclerosis, (2) lymphocyte rich, (3) mixed cellularity, (4) lymphocyte depleted, and (5) nodular lymphocyte predominant [12]. In NHL, parafollicular or marginal zone distribution of B cells occurs in nodal marginal zone b cell lymphoma, while complete, partial, sinus, or interfollicular involvement with variable cytology occurs in diffuse large B cell lymphoma, not otherwise specified [17].

Clinical features suggestive of malignant etiology of CLA include:

Lymphadenopathy is a detectable physical finding in up to 82 % and 69 % of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) cases, respectively, but it could also be seen in almost any autoimmune disorder. In these disorders, adenopathy of cervical nodes ranks second in frequency after axillary lymphadenopathy [41]. Histopathologically, inflamed nodes show reactive follicular hyperplasia, polyclonal plasma cell infiltration with occasional mitosis in the interfollicular area, moderate vascular proliferation, and no compression of reticulin fibers; this is to differentiate it from lymphoma in which interfollicular area shows many mitosis, scarce plasma cells, and compressed reticulin fibers [42].

When present, cervical lymphadenopathy is usually associated with axillary and/or inguinal lymphadenopathy. Lymph nodes are usually multiple, relatively small, soft, mobile, and not tender [43]. Diagnosis should be made on the ground of relevant clinical and laboratory criteria. Polyarthritis of small joints, lasting more than 6 weeks together with elevation of serum rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), and acute phase reactants (APR) is diagnostic for RA [44]. Presence of malar rash, discoid rash, nonerosive arthritis, photosensitivity, oral ulcers, and renal, neurologic, and hematologic disorders and elevated antinuclear antibodies and anti-DNA antibodies are diagnostic of SLE [45]. Dryness of the mouth and eyes is suggestive of Sjogren’s syndrome [46].

Sahlmann et al. [47] reported that cervical lymphadenopathy (levels II–IV, VI) occurred in more than 80 % of patients with autoimmune thyroiditis (AIT). Similarly, cervical lymphadenopathy was detected in 23 % of cases of Hashimoto’s thyroiditis (HT) [48]. Graves’ disease has also been reported to be associated with cervical lymphadenopathy [49, 50]. Pathology is reactive lymphoid hyperplasia. Therefore, AIT including HT should be included in differential diagnosis of patients with thyroid nodes and cervical LNs. Presence of cervical lymphadenopathy in a patient with clinical features of chronic adrenal insufficiency should alert the physician to the possibility of secondary adrenal involvement or to the very rare entity of primary adrenal lymphoma [51, 52].

Certain medications can cause diffuse lymphadenopathy; of which phenytoin-induced lymphadenopathy is the most widely described in the literature. The reaction tends to occur few months after initiation of therapy and usually disappear within weeks after stopping drug administration. Pathophysiology is thought to be due to medication-induced immunologic disturbances, including reduced humoral and cellular immunity. Pathology usually reveals partial or complete effacement of the lymph node architecture by polymorphous infiltration of lymphocytes, plasma cells, and eosinophils [53, 54].

Phenytoin, in particular, has also been associated with a characteristic nodal pathology, termed pseudolymphoma. Differentiation from lymphoma is based on the absence of clonal proliferation of T cells. Clinically, cervical adenopathy tends to be bilateral and usually part of generalized lymphadenopathy. Condition is often associated with fever, rash, and eosinophilia. A high index of suspicion should always be kept since the condition can be easily confused with lymphoma. History of phenytoin exposure, improvement on phenytoin discontinuation, and pathological examination of a surgically excised lymph node are the clues to correct diagnosis [55].