Diagnostic Dilemmas in FNAC Practice: Lymphoid Infiltrates 5

Chapter 5 Diagnostic Dilemmas in FNAC Practice: Lymphoid Infiltrates 5 Contents Diagnostic dilemmas associated with the pre- sence of lymphoid cells in FNAC samples are 5.1. Granulomatous Infiltrates.................91 usually considered to be associated with the di- 5.1.1 Tuberculous Lymphadenitis ................91 agnosis of lymphomas. However, whilst the ma- 5.1.2 Sarcoidosis ...............................92 5.1.3 Kikuchi-Fujimoto Disease..................92 jority of lymphomas can be diagnosed without 5.1.4 Cat-Scratch Disease .......................94 difficulty, there are other aspects of lymphoid 5.1.5 Leishmania Lymphadenitis .................94 infiltrates in FNAC samples that may be either 5.1.6 Kimura’s disease ..........................95 misleading or difficult. This chapter gives some 5.1.7 Sinus Histiocytosis examples of the conditions where observing the with Massive Lymphadenopathy ............96 5.1.8 Foreign-Body Granulomatous details of lymphoid infiltrates may be important Inflammatory Response....................96 in making the diagnosis. 5.1.9 Malignant Lymphomas ....................97 5.2 Lymphoid Infiltrates in Extranodal Sites ....99 5.2.1 Lymphoid Infiltrates in the Thyroid..........99 5.1. Granulomatous Infiltrates 5.2.2 Lymphoid Processes in the Salivary Gland . 103 5.2.3 Lymphoid Infiltrates of the Orbit ...........105 5.2.4 Lymphoid Lesions in the Breast ............107 Granulomatous infiltrates refer to the lymphoid infiltrates in which aggregates of histiocytes/epi- 5.3 Neoplasms Containing Lymphocytes ......107 thelioid cells and/or multinucleate giant histi- 5.3.1 Dilemmas in the Cytological Diagnosis ocytes are present. The spectrum of conditions of Lymphomas...........................108 showing this change is wide and includes both 5.3.2 Solid Neoplasms Containing Lymphocytes . 109 benign and malignant processes. Granulomata References ....................................110 represent either the main pathology or a secondary reaction to it. In both instances, their pre- sence is highly relevant. Most commonly, granulomata point to additional features that may lead to a correct diagnosis. The following are examples of some of the granulomatous conditions encountered in FNAC cytology. 5.1.1 Tuberculous Lymphadenitis This is probably the most commonly seen granulomatous lymphadenitis in FNAC practice. Alt- hough a relatively rare cause of lymphadenopathy in adults in the Western world, in HIV-positive African patients with superficial lymphadenopa- 92 thy, it is more common than is generally appre- sarcoidosis is not capable of differentiating the ciated [1]. Regardless of the geographic distribu- lesions from TB on the basis of imaging alone. tion, in the absence of pulmonary tuberculosis, It may be diagnosed from EUS-FNAC of lymph tuberculous lymphadenitis is sometimes difficult nodes by demonstrating non-caseating granu- to differentiate clinically from other diseases. lomata without necrosis. Annema et al. report Although the classical FNAC features of epithe- an accuracy rate of 82% when using FNAC for lioid cells, multinucleate giant cells and caseous the final diagnosis of sarcoidosis [14]. Aspirated necrosis are present in most cases, the early le- material can be sent for mycobacterial culture sions may not be so apparent (Fig. 5.1). FNAC [15, 16]. Sarcoidosis may affect multiple other predicts the correct diagnosis in 62% of cases sites that can potentially be subjected to FNAC, 5 and has a high false-negative rate (38%) due to including the salivary glands (Fig. 5.2). Caution the absence of granulomata/necrosis in smears is needed, however, since granulomatous trans- from cases of early tuberculosis [2]. Detection of formation of the lymphoid stroma resembling AFB is positive in less than half of cases [3]. In sarcoidosis may be seen in the lymphoid compo- addition, antiretroviral therapy has introduced nent of Warthin’s tumour of the salivary gland. It new morphological patterns of mycobacterial is rare, may be associated with previous FNAC infection as part of the seroconversion that oc- and should be considered within the spectrum of curs following treatment [4, 5]. Presently, as well secondary changes in adenolymphoma [17]. as the detection of AFB, PCR of mycobacteria is used as the gold standard for diagnosis. The best results are achieved when FNAC and PCR are used in combination [1, 3, 6–13]. Fig. 5.2 FNAC parotid. Sarcoidosis. Sarcoidosis may affect multiple sites that are potentially subjected to FNAC, including the salivary glands Fig. 5.1 5.1.3 Kikuchi-Fujimoto Disease FNAC lymph node. Granulomatous lymphadenitis. Ag- gregates of epithelioid cells in large aggregates in a case of tuberculous lymphadenitis Also known as histiocytic necrotising lymphadenitis, this is a benign disorder that is characte- rised histologically by necrotic foci surrounded 5.1.2 Sarcoidosis by histiocytic aggregates, and with the absence of neutrophils. The disease most commonly affects young women. It has a worldwide distribution, This is a chronic multisystem granulomatous but with a higher prevalence among Asiatic peo- disease that is often diagnosed after a finding ple. Its cause is unknown and its exact pathoge- of hilar and mediastinal lymphadenopathy on a nesis has not yet been clarified. Many investiga- chest X-ray. EUS of mediastinal lymph nodes in tors have postulated a viral aetiology, connecting Lymphoid Infiltrates Chapter 5 93 it with Epstein-Barr virus, human herpes sim- tic carcinoma, toxoplasmosis and infectious mo- plex virus 6 Parvo B 19 and with toxoplasmic nonucleosis, or even a submandibular tumour infection. Kikuchi-Fujimoto disease is usually [23, 24]. Kikuchi’s lymphadenitis is an uncom- manifested by acute tender, cervical lymphade- mon, self-limited and perhaps underdiagnosed nopathy, predominantly in the posterior cervical process with an excellent prognosis. Accurate region, a low-grade fever and is associated with clinicopathological recognition is crucial, parti- lymphopaenia, splenomegaly and hepatomega- cularly because it can be mistaken for malignant ly with abnormal liver function tests, arthralgia lymphoma [18–32]. and weight loss [18]. The disease has the tenden- cy toward spontaneous remission, with a mean duration of 3 months. Single recurrent episodes of Kikuchi’s disease have been reported with gaps of many years between episodes. Kikuchi‘s disease has been reported to precede, coexist with or follow the diagnosis of systemic lupus erythe- matosus (SLE) [18, 19]. Final diagnosis is usually established on the basis of lymph node biopsy. As Kikuchi’s disease does not have any classical clinical features or laboratory characteristics, it may lead to diagnostic confusion and errone- ous treatment. FNAC smears contain a random polymorphous lymphoid population: plasmacytoid monocytes, immunoblasts, small and large lymphocytes, abundant karyorrhectic debris and prominent histiocytes, many of which are small and eccentrically placed, have crescent nuclei and are thought to be characteristic of Kikuchi’s [20] (Fig. 5.3). The overall accuracy of FNAC diagnosis in a series by Tong et al. was 56.25%. They found that morphological overlap between Kikuchi’s and tuberculous lymphadenitis could have been the reason for the false-negative dia- gnoses [21]. Some of the cases do not show typical cytological findings and are indistinguishable from other non-specific reactive lymphadeno- Fig. 5.3 pathies. However, when typical cytological fin- FNA lymph node. Kikuchi’s lymphadenitis. a FNAC dings are present in an adequate clinical context smears contain abundant karyorrhectic debris and pro- (cervical nodes in young patients), a precise di- minent histiocytes, many of which are small and eccen- agnosis is possible, avoiding unnecessary biopsy trically placed, crescent-shaped nuclei and are thought to be characteristic of Kikuchi’s. b A polymorphous lym- procedures [22]. Histological findings include phoid population consists of plasmacytoid monocytes, paracortical areas of coagulative necrosis with immunoblasts, and small and large lymphocytes abundant karyorrhectic debris. Karyorrhectic foci consist of various types of both histiocytes When SLE patients develop lymphadenopathy, and lymphocytes, as described above. There is FNAC helps differentiate lupus adenopathy from an abundance of T cells with predominance of infectious conditions such as tuberculous adeni- CD8+ over CD4+ T cells. Lymphadenopathy in tis, and from Kikuchi‘s lymphadenitis although, a patient with fever of unknown origin could be as mentioned earlier, the latter may be associated clinically mistaken for a lymphoma, lymphade- with or mimic SLE changes [19, 29, 30]. FNAC nitis associated with SLE, tuberculosis, metasta- in these cases shows predominantly typical and 94 atypical immunoblasts, plasma cells, occasional tive organisms in 69% of cases and is not limited Reed-Sternberg-like cells and dispersed haema- to those preparations with suppurative granulo- toxylin bodies. Smears are negative for AFB. A mata [36]. Numerous atypical manifestations of similarity between lupus adenopathy to the mul- the disease have been described, and these often ticentric Castleman‘s disease has been described lack the characteristic superficial lymphadeno- [33–35]. pathy and inoculation site papule. These atypical forms may be misdiagnosed initially as other infectious processes or neoplasms [37–40]. 5.1.4 Cat-Scratch Disease 5 Cat-scratch disease was initially described in 1931, but the aetiologic

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