Cytodiagnosis of Lesions Presenting as Salivary Gland Swellings: A Report of Seven Cases May K.M. Chan, M.R.C.Path(UK), M.I.A.c., and Lloyd J. McGuire, F.R.C.P.A., F.I.A.C.
The cytologic and histologic findings of seven cases presenting clinically as salivary gland swellings are described. These included two cases ofpilomatrixoma of skin in the parotid region, two cases ofneurilemtnoma in the submandibular area, a case of Kimura s.’ disease in the peri-mandibular gland lymphoid tissue, a case of Castleman’s di.sease in intraparotid lymph node, and a case of branchial cleft cyst in the parotid region. It is important to recognize lesions that masquerade as salivary gland tumors so that misdiagnosi.s and overdiagnosis on smears can be avoided and the patients can be treated appropriately. Diagn Cytopathol 1992;8: 439-443. ;c) 1992 Wiley-Lisc, Inc. Key Words: Pilomatrixoma; Neurilemmoma; Kimura’s disease; Castleman’s disease; Branchial cleft cyst; Salivary gland; Cytology
Neck masses may present clinically as apparent salivary gland lesions and yet arise from other nearby structures such as the dermis, skin appendages, soft tissue, and perisalivary lymphoid tissue. Furthermore skin appendage tumors may mimic salivary gland lesions cytologically. We describe the fine needle aspiration (FNA) findings and histological diagnoses of seven cases in which the patients presented clinically with salivary gland swelling. These cases were discovered during the review of salivary gland lesions in our hospital from 1985 to mid-1990. The clinical features and pathology results are summarized in Table I.
Case Reports Case I and 2: Pilomatrixoma A 42 year old man and a 17 year old woman both presented with unilateral parotid masses. Fine needle aspiration was done in both cases by surgeons using 21 gauge needles. The first case was diagnosed as pleomorphic adenoma with squamous metaplasia and the second case was diagnosed as negative for malignancy without giving a definitive diagnosis. Both lesions were excised and histology showed pilomatrixoma of skin. The first case has been described previously. * Histology showed basaloid cells, keratinized squamous cells, ghost cells, multinucleated giant cells, keratin material, and calcium which are typical of pilomatrixoma. Review of the smears showed cellular clusters consisting of tightly packed cells with large nuclei and scanty cytoplasm, hypocellular clusters consisting of cells with abundant cytoplasm with indistinct cell borders, keratin material, and multinucleated giant cells (Fig. 1).
‘2’
Received January 27, 1991. Accepted November 27, 1991. From the Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong. Address reprint requests to May K.M. Chan, M.K.C.Path, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Shatin, N.T., Hong Kong.
I W ? WII I : Y ~ I15s. INC
Case 3 and 4: Neurilemmoma A 20 year old man and a 49 year old woman both presented with unilateral submandibular masses. The first case was diagnosed as pleomorphic adenoma and the second case was diagnosed correctly as neurilemmoma on smears. Both lesions were finally excised. One of the tumors measured 5 x 3 x 2 cm, with slightly mucoid cut surface. Histology showed typical neurilemmoma. Review of the first case showed spindle cells with fine nuclear chromatin embedded in myxoid stroma. Palisading nuclei were not conspicuous. Toluidine blue stain was performed and showed the metachromatic myxoid stroma. It was these fragments that were mistaken as stromal component in pleomorphic adenoma. Careful search did not reveal any epithelial clusters which are nearly always present
Diagnostic Cytopathology, Vol 8, No 5
439
CHAN AND McGUIRE Cyto-Histologic Diagnoses of the Seven Case\
Table I. Cu.se No. 1
Sex
Age. vcur.s
M
42
l'leomorphic adenoma with squamou.; nietaplasia
Pilomatrixoma
Cvtologic diagnosir
Ilictologic diuKno.si.s
2
F
17
Negative for malignancy
Pilomatrixoma
3
M
20
Pleomorphic adenoma
Neurilenimonia
4
F
49
Neurilemnloma
Neurilemmoma
5
M
55
Lymphoid hyperplasia
Kimura's disease
6
F
43
D D x of benign lymphoid levon and Warthin's tumor
Cactlernan's diwase
7
F
16
Consiitenr with branchial cleft cyst
Branchial cleft cyst
Fig. 2. Smear of a rleurilemmoma (case 3) showing the palisaded nuclei (Papanicolaou stain, x 300).
and areas characterized by loose myxoid stroma corresponding to Antoni-B areas in histologic section. Nuclear atypia was encountered in both cases which should not be alarming as it is not unusual in neurilemmoma.
Case 5: Kim ura 's Disease A 5 5 year old man presented with right submandibular gland swelling of 3 cm diameter for a few years. FNA smears showed many mature lymphoid cells, some occurring in clusters, mixed with many eosinophils (Fig. 3A). Some clusters resembled germinal centers. Vessels lined by plump endothelial cells, hyaline material, and fibrosis were nresent (Fig. 3 B l There were also manv normal salivary gland acini. Lymphoepithelial islands typically Seen in benign lymphoepithelial lesions were not seen.The F N A diagnosis was lymphoid hyperplasia. The lesion was finally excised and showed salivary gland measuring 3 cm in diameter and two lymph nodes each measuring 2 cm in diameter. Histology showed typical Kimura's disease involving perisalivary gland lymphoid tissue and sparing the submandibular gland. Kimura's disease is a chronic inflammatory condition producing subcutaneous tumor-like \
Fig. 1. Cytology cnimr of pilomatrixoma (casc I ) hhowing basdoid celIs (thin arrow), kcrniitii/rtl squanious cell (arrowhead), keratin (double arrow), and nlult~tlticleatcdgiant cell (thick arrow) (Papauicolaou s t t i i i i ,
x 150)
in pleomorphic adenoma. The second case was more straightforward partly because of the experience gained from the first case. In this case, the smear showed typical areas with spindle cells displaying nuclear palisading (Fig. 2), corresponding to Antoni-A areas in histologic sections, 440
Diugriostic Cytopathology, Vol 8, No 5
"
I
CYTODIAGNOSIS OF SALIVARY GLAND SWELLINGS
tive diagnosis was not given. Differential diagnoses of benign lymph node aspirate and Warthin’s tumor were given. The lesion was surgically excised which showed a fleshy nodule measuring 3.5 x 1.5 x 1.5 cm, in the center of the parotid gland. Frozen section was performed and showed lymphoid lesion which the diagnosis was deferred until permanent section and special stains were available. Final histology showed a typical case of Castleman’s disease (angiofollicular lymph node hyperplasia), hyaline vascular type, involving an intraparotid lymph node with sparing of the salivary gland. The node contains many lymphoid follicles with typical “onion-skin” appearance. Hyaline material is seen inside follicles, and in between the follicles are many capillaries. Review of the smears did not show features diagnostic of Castleman’s disease, and neither did careful search show typical oncocytic cells diagnostic of Warthin’s tumor. The overall smear, however, with the presence of mainly small mature lymphocytes, did favor a reactive lymphoid lesion, the definitive diagnosis of which would depend on histology.
Case 7: Branchial Cleft Cyst
Fig. 3. Cytology smear of Kimura’s disease (case 5). (A) A mixture of lymphocytes and eosinophils (arrowheads). (B) Plump endothelial cell\ (arrows) (Papanicolaou stain, x 300).
nodule chiefly in the head and neck region, and sometimes in superficial lymph nodes and parotid gland.”’ Histologically, it is characterized by lymphoid follicles, intense aggregates of eosinophils which sometimes form small abscesses, vascular proliferation, and fibrosis. None of the above features is specific, but a combination of these features is highly characteristic of Kimura’s disease. Likewise, in cytology smears, the presence of many mature lymphocytes, eosinophils, vascular proliferation, and fragments of fibrous tissue are highly suggestive of Kimura’s disease.
Case 6: Angiofollicular Lymph Node Hyperplasia (Castleman’s Disease) A 43 year old woman presented with 3 years history of right parotid gland swelling of 3.5 cm diameter. F N A smears showed many lymphocytes, most of which were small and mature. Many capillaries and some hyaline masses were also seen. Germinal centers were not seen. There were no eosinophils and no granulomas. A defini-
A 16 year old girl presented with a right parotid mass for 2 years. The mass measured 2.5 x 2 x 2 cm. F N A smears showed keratin material, mature squamous cells (Fig. 4A), and lymphocytes (Fig. 4B). The smear diagnosis was consistent with branchial cleft cyst. The lesion was finally excised; histology shows keratin material inside the cyst and the wall was formed by multi-layered squamous epithelium, lymphoid tissue, and collagen.
Discussion Lesions situated in the angle of jaw and submandibular region can arise from major salivary glands: the parotid and the submandibular gland, skin appendages, soft tissue, and peri-salivary gland lymphoid tissue. Occasionally, developmental abnormalities such as branchial cleft cyst can occur at these sites. The differential diagnoses to the lesions we have described will be discussed. Pilomatrixoma, which is characterized by presence of basaloid cells, keratinizing squamous cells, ghost cells, and keratin material in the smear, should not be mistaken as metastatic squamous cell carcinoma. Such overdiagnosis would result in unnecessary investigation, surgery, and patient anxiety. Cells in pilomatrixoma are benign looking, and nuclear chromatin is fine with inconspicuous nucleoli. One should always look for features such as pleomorphism, coarse chromatin, and prominent nucleoli before diagnosing malignancy. For neurilemmoma, there are typical features 4,8 such as palisading nuclei, Verocay bodies, and loose myxoid stroma which should make diagnosis relatively straightforward. However, there are other lesions which also exhibit palisading nuclei such as in some cases of pleomor-
’
Diugtivstic Cylopotholvgy, Vvl 8, No 5
44 1
CHAN AND McGUIRE
Castleman’s disease (angiofollicular lymph node hyperplasia) was first described by Castleman and associates. ” It can be a localized lesion in mediastinum, cervical and axillary region, skeletal muscle, lung, abdomen, and retroperitoneum. ‘**I3 There are only two reports on its OCcurrence in the parotid region in the English literature. Ours appears to be the third reported case. Histologically, two distinct types (hyaline-vascular and plasma cell) have been described and our case belongs to the hyaline-vascular type. There is up to date no report on the cytologic findings of this disease. Review of the F N A smears of our case shows predominently small lymphocytes, with scattered clumps of histiocytes, tingiblebody macrophages, and many fragments of capillaries. The typical histologic follicular pattern and “onion-skin’’ arrangement of lymphocytes surrounding follicles are not seen on smears. Thus based on the F N A smears, the differential diagnoses would include benign lymphoid hyperplasia, l 6 follicular lymphoma, and even Hodgkin’s disease. For follicular lymphoma, the cells should be more monomorphic and tingible-body macrophages are scanty or absent. Immunohistochemistry will show a polytypic cell population in Castleman’s disease and monoclonality in lymphoma. The cytologic diagnosis of Hodgkin’s disease will depend on the finding of Reed-Sternberg cells and/or Hodgkin cells. Finally, a search for oncocytic cells and lymphoepithelial island is required to exclude Warthin’s tumor and lymphoepithelial lesion, respectively. Branchial cleft cysts are located in the anterolateral region of the neck. Those related to the first cleft appear in the preauricular area or beneath the posterior half of the mandible. Those related to the second cleft appear just anterior to the sternocleidomastoid muscle. Others are in the lower neck region. It is the cyst related to the first cleft defect that mimics parotid gland lesion. Like pilomatrixoma, it should not be diagnosed as well-differentiated squamous cell carcinoma. The squamous cells in branchial cyst are uniform and bland with fine nuclear chromatin o r pyknotic nuclei. The clinical detail in such a case is very important because branchial cleft cyst occurs in younger patients while squamous cell carcinoma occurs usually in older patients. In summary, we think it is important that one should recognise the mimickers of salivary gland lesions for three reasons. First, salivary gland neoplasm is uncommonly encountered in individual cytology practice which means that experience is difficult to accumulate. Second, in some centers where the surgeons or the oncologists perform the F N A , the pathologists may not know the exact site, plane, and consistency of the lesions which may affect the correct interpretation. I n these circumstances, the pathologist may try to fit the smear findings into that of primary of secondary salivary neoplasm as happened in our case 1 ‘‘315
’*
Fig. 4. Cytology smear of a brunchial cleft cyst (case 7) showing (A) mature squamous cells and (B) clump of lymphocytes (hematoxylin & rosin \lain, >~300).
phic adenoma’ and leiomyoma. Myxoid stroma is also present in pleomorphic adenoma. Thus the whole smear pattern should be taken into consideration in diagnosis. Furthermore, an enquiry into sensation of pain during aspiration is helpful as it is known that neurilemmoma may be painful to aspirate. Kimura’s disease is characterized by the presence of mature lymphocytes, eosinophils, vessels lined by plump endothelial cells, and fibrosis. 4-‘ Similar features can be encountered in angiolymphoid hyperplasia with eosinophilia (ALHE) which is considered a different entity because of different clinical presentation and histologic features. 4h The main histologic difference is that ALHE has exuberant angiomatoid proliferation and uncanalized masses of endothelial cells. Likewise in cytology smears, A L H E contains predominantly epithelioid endothelial cells and eosinophils. l o Another differential diagnosis to consider is healing abscess which sometimes yields many lymphocytes, eosinophils, and connective tissue, but it also contains plenty of polymorphs and histiocytes which are lacking in Kimura’s disease. 442
Diugnortic Cyroputhology, Val 8, No 5
CYTODIAGNOSIS OF SALIVARY GLAND SWELLINGS
and 3 where a pilomatrixoma and a neurilemmorna were diagnosed as pleomorphic adenoma. Last, the rnanagement of these rnirnickers may be quite different from that of primary salivary gland neoplasm. Usually only local excision is required and the salivary gland may be spared.
Acknowledgments We thank Dr. C. Hsu for reviewing the manuscript and Mrs. Prisica Cheng for typing the manuscript.
References I . KatL AD. Unusual lesions of the parotid gland. J Surg Oncol 1975;7: 2 1 9-23 5 . 2. Chan MKM, McGuire LJ. Fine needle aspiration cytodibgnosis of an unusual parotid mass. Acta Cytol (Baltimore) 1989;33:27&276. 3. Bondeson L, Lindholm K, Thorstenson S. Benign dermal eccrine cylindroma-a pitfall in the cytologic diagnosis of adenoid cystic carcinoma. Acta Cytol (Baltimore) 1983;27:326-328. 4. Kung ITM, Gibson JB, Bannatyne PM. Kimura’s disease: a clinicopathological study of 21 cases and its distinction from angiolymphoid hyperplasia with eosinophilia. Pathology 1984;16:2944. 5. Hui PK, Chan JK, Ng CS, et al. Lymphadenopathy of Kimura’s disease. Am J Surg Pathol 1989;13:177-186. 6. Chan JK, Hui PK, Ng CS, et al. Epithelioid haemangioma (angiolymphoid hyperplasia with eosinophilia) and Kimura’s disease in Chinese. Histopathology 1989; 15:557-574. 7. Woyke S, Olszewski W, Eichelkvault A. Pilomatrixoma-a pitfall in the aspiration cytology of skin tumors. Acta Cytol (Baltimore) 1982; 26: 189-194.
8. Ramzy 1. Benign Schwannoma: demonstration of Verocay bodies using fine needle aspiration. Acta Cytol (Baltimore) IS77;21:316319. 9. Thackray AC, Lucus RB. Tumors of the major salivary glands. AFIP 1974:24-26 10. Pettinato G, Insabato L, De Chiara A, et al. Fine needle aspiration cytology of angiolymphoid hyperplasia with eosinophilia: a case report with electron microscopy and immunohistochemistry. Diagn Cytopathol 1989;5:88-94. 1 1 . Castleman 9 , Iverson L, Menendez V. Localized mediastlnal lymph node hyperplasia resembling thymomas. Cancer 1956;9:822-830. 12. Tung KSK, McCormack LJ. Angiomatous lymphoid hamartoma. Cancer 1967;20:525-536. 13. Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and plasma cell types of giant lymph node hyperplasia of mediastilium and other locations. Cancer 1972;29:670-683. 14. Woolgar JA, Hook PCG. Angiofollicular lymph node hyperplasia of the parotid. Br J Oral Maxillofac Surg 1991;29:198-200. 15. Prasad HSK, Sankaran V, Raman ML, Veliath AJ, Ananthakrishnan N. Giant lymph node hyperplasia of the parotid region. Indian J Pathol Microbiol 1988;31:68. 16. O’Dowd GJ, Frable WJ, Behm FG. Fine needle aspiration cytology of benign lymph node hyperplasia. Diagnostic significance of lymphohistiocytic aggregates. Acta Cytol (Baltimore) 1985;29:55+ 558.
17. Jones EL, Crocker J, Gregory J, et al. Angiofollicular lymph node hyperplasia (Castleman’s disease): an immunohistochemical and enzyme-histochemical study of the hyaline-vascular form of lesion. J Pathol 1984;144:I3 1-147. 18. Das DK, Gupta SK, Datta BN, Sharma SC. Fine needle aspiration cytodiagnosis of Hodgkin’s disease and its subtypes: I . Scope and limitations. Acta Cytol (Baltimore) 1990;34:329-336.
Diugriostic Cyropathology, Vol 8, No 5
443
The cytologic and histologic findings of seven cases presenting clinically as salivary gland swellings are described. These included two cases ofpilomatrixoma of skin in the parotid region, two cases ofneurilemtnoma in the submandibular area, a case of Kimura s.’ disease in the peri-mandibular gland lymphoid tissue, a case of Castleman’s di.sease in intraparotid lymph node, and a case of branchial cleft cyst in the parotid region. It is important to recognize lesions that masquerade as salivary gland tumors so that misdiagnosi.s and overdiagnosis on smears can be avoided and the patients can be treated appropriately. Diagn Cytopathol 1992;8: 439-443. ;c) 1992 Wiley-Lisc, Inc. Key Words: Pilomatrixoma; Neurilemmoma; Kimura’s disease; Castleman’s disease; Branchial cleft cyst; Salivary gland; Cytology
Neck masses may present clinically as apparent salivary gland lesions and yet arise from other nearby structures such as the dermis, skin appendages, soft tissue, and perisalivary lymphoid tissue. Furthermore skin appendage tumors may mimic salivary gland lesions cytologically. We describe the fine needle aspiration (FNA) findings and histological diagnoses of seven cases in which the patients presented clinically with salivary gland swelling. These cases were discovered during the review of salivary gland lesions in our hospital from 1985 to mid-1990. The clinical features and pathology results are summarized in Table I.
Case Reports Case I and 2: Pilomatrixoma A 42 year old man and a 17 year old woman both presented with unilateral parotid masses. Fine needle aspiration was done in both cases by surgeons using 21 gauge needles. The first case was diagnosed as pleomorphic adenoma with squamous metaplasia and the second case was diagnosed as negative for malignancy without giving a definitive diagnosis. Both lesions were excised and histology showed pilomatrixoma of skin. The first case has been described previously. * Histology showed basaloid cells, keratinized squamous cells, ghost cells, multinucleated giant cells, keratin material, and calcium which are typical of pilomatrixoma. Review of the smears showed cellular clusters consisting of tightly packed cells with large nuclei and scanty cytoplasm, hypocellular clusters consisting of cells with abundant cytoplasm with indistinct cell borders, keratin material, and multinucleated giant cells (Fig. 1).
‘2’
Received January 27, 1991. Accepted November 27, 1991. From the Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong. Address reprint requests to May K.M. Chan, M.K.C.Path, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Shatin, N.T., Hong Kong.
I W ? WII I : Y ~ I15s. INC
Case 3 and 4: Neurilemmoma A 20 year old man and a 49 year old woman both presented with unilateral submandibular masses. The first case was diagnosed as pleomorphic adenoma and the second case was diagnosed correctly as neurilemmoma on smears. Both lesions were finally excised. One of the tumors measured 5 x 3 x 2 cm, with slightly mucoid cut surface. Histology showed typical neurilemmoma. Review of the first case showed spindle cells with fine nuclear chromatin embedded in myxoid stroma. Palisading nuclei were not conspicuous. Toluidine blue stain was performed and showed the metachromatic myxoid stroma. It was these fragments that were mistaken as stromal component in pleomorphic adenoma. Careful search did not reveal any epithelial clusters which are nearly always present
Diagnostic Cytopathology, Vol 8, No 5
439
CHAN AND McGUIRE Cyto-Histologic Diagnoses of the Seven Case\
Table I. Cu.se No. 1
Sex
Age. vcur.s
M
42
l'leomorphic adenoma with squamou.; nietaplasia
Pilomatrixoma
Cvtologic diagnosir
Ilictologic diuKno.si.s
2
F
17
Negative for malignancy
Pilomatrixoma
3
M
20
Pleomorphic adenoma
Neurilenimonia
4
F
49
Neurilemnloma
Neurilemmoma
5
M
55
Lymphoid hyperplasia
Kimura's disease
6
F
43
D D x of benign lymphoid levon and Warthin's tumor
Cactlernan's diwase
7
F
16
Consiitenr with branchial cleft cyst
Branchial cleft cyst
Fig. 2. Smear of a rleurilemmoma (case 3) showing the palisaded nuclei (Papanicolaou stain, x 300).
and areas characterized by loose myxoid stroma corresponding to Antoni-B areas in histologic section. Nuclear atypia was encountered in both cases which should not be alarming as it is not unusual in neurilemmoma.
Case 5: Kim ura 's Disease A 5 5 year old man presented with right submandibular gland swelling of 3 cm diameter for a few years. FNA smears showed many mature lymphoid cells, some occurring in clusters, mixed with many eosinophils (Fig. 3A). Some clusters resembled germinal centers. Vessels lined by plump endothelial cells, hyaline material, and fibrosis were nresent (Fig. 3 B l There were also manv normal salivary gland acini. Lymphoepithelial islands typically Seen in benign lymphoepithelial lesions were not seen.The F N A diagnosis was lymphoid hyperplasia. The lesion was finally excised and showed salivary gland measuring 3 cm in diameter and two lymph nodes each measuring 2 cm in diameter. Histology showed typical Kimura's disease involving perisalivary gland lymphoid tissue and sparing the submandibular gland. Kimura's disease is a chronic inflammatory condition producing subcutaneous tumor-like \
Fig. 1. Cytology cnimr of pilomatrixoma (casc I ) hhowing basdoid celIs (thin arrow), kcrniitii/rtl squanious cell (arrowhead), keratin (double arrow), and nlult~tlticleatcdgiant cell (thick arrow) (Papauicolaou s t t i i i i ,
x 150)
in pleomorphic adenoma. The second case was more straightforward partly because of the experience gained from the first case. In this case, the smear showed typical areas with spindle cells displaying nuclear palisading (Fig. 2), corresponding to Antoni-A areas in histologic sections, 440
Diugriostic Cytopathology, Vol 8, No 5
"
I
CYTODIAGNOSIS OF SALIVARY GLAND SWELLINGS
tive diagnosis was not given. Differential diagnoses of benign lymph node aspirate and Warthin’s tumor were given. The lesion was surgically excised which showed a fleshy nodule measuring 3.5 x 1.5 x 1.5 cm, in the center of the parotid gland. Frozen section was performed and showed lymphoid lesion which the diagnosis was deferred until permanent section and special stains were available. Final histology showed a typical case of Castleman’s disease (angiofollicular lymph node hyperplasia), hyaline vascular type, involving an intraparotid lymph node with sparing of the salivary gland. The node contains many lymphoid follicles with typical “onion-skin” appearance. Hyaline material is seen inside follicles, and in between the follicles are many capillaries. Review of the smears did not show features diagnostic of Castleman’s disease, and neither did careful search show typical oncocytic cells diagnostic of Warthin’s tumor. The overall smear, however, with the presence of mainly small mature lymphocytes, did favor a reactive lymphoid lesion, the definitive diagnosis of which would depend on histology.
Case 7: Branchial Cleft Cyst
Fig. 3. Cytology smear of Kimura’s disease (case 5). (A) A mixture of lymphocytes and eosinophils (arrowheads). (B) Plump endothelial cell\ (arrows) (Papanicolaou stain, x 300).
nodule chiefly in the head and neck region, and sometimes in superficial lymph nodes and parotid gland.”’ Histologically, it is characterized by lymphoid follicles, intense aggregates of eosinophils which sometimes form small abscesses, vascular proliferation, and fibrosis. None of the above features is specific, but a combination of these features is highly characteristic of Kimura’s disease. Likewise, in cytology smears, the presence of many mature lymphocytes, eosinophils, vascular proliferation, and fragments of fibrous tissue are highly suggestive of Kimura’s disease.
Case 6: Angiofollicular Lymph Node Hyperplasia (Castleman’s Disease) A 43 year old woman presented with 3 years history of right parotid gland swelling of 3.5 cm diameter. F N A smears showed many lymphocytes, most of which were small and mature. Many capillaries and some hyaline masses were also seen. Germinal centers were not seen. There were no eosinophils and no granulomas. A defini-
A 16 year old girl presented with a right parotid mass for 2 years. The mass measured 2.5 x 2 x 2 cm. F N A smears showed keratin material, mature squamous cells (Fig. 4A), and lymphocytes (Fig. 4B). The smear diagnosis was consistent with branchial cleft cyst. The lesion was finally excised; histology shows keratin material inside the cyst and the wall was formed by multi-layered squamous epithelium, lymphoid tissue, and collagen.
Discussion Lesions situated in the angle of jaw and submandibular region can arise from major salivary glands: the parotid and the submandibular gland, skin appendages, soft tissue, and peri-salivary gland lymphoid tissue. Occasionally, developmental abnormalities such as branchial cleft cyst can occur at these sites. The differential diagnoses to the lesions we have described will be discussed. Pilomatrixoma, which is characterized by presence of basaloid cells, keratinizing squamous cells, ghost cells, and keratin material in the smear, should not be mistaken as metastatic squamous cell carcinoma. Such overdiagnosis would result in unnecessary investigation, surgery, and patient anxiety. Cells in pilomatrixoma are benign looking, and nuclear chromatin is fine with inconspicuous nucleoli. One should always look for features such as pleomorphism, coarse chromatin, and prominent nucleoli before diagnosing malignancy. For neurilemmoma, there are typical features 4,8 such as palisading nuclei, Verocay bodies, and loose myxoid stroma which should make diagnosis relatively straightforward. However, there are other lesions which also exhibit palisading nuclei such as in some cases of pleomor-
’
Diugtivstic Cylopotholvgy, Vvl 8, No 5
44 1
CHAN AND McGUIRE
Castleman’s disease (angiofollicular lymph node hyperplasia) was first described by Castleman and associates. ” It can be a localized lesion in mediastinum, cervical and axillary region, skeletal muscle, lung, abdomen, and retroperitoneum. ‘**I3 There are only two reports on its OCcurrence in the parotid region in the English literature. Ours appears to be the third reported case. Histologically, two distinct types (hyaline-vascular and plasma cell) have been described and our case belongs to the hyaline-vascular type. There is up to date no report on the cytologic findings of this disease. Review of the F N A smears of our case shows predominently small lymphocytes, with scattered clumps of histiocytes, tingiblebody macrophages, and many fragments of capillaries. The typical histologic follicular pattern and “onion-skin’’ arrangement of lymphocytes surrounding follicles are not seen on smears. Thus based on the F N A smears, the differential diagnoses would include benign lymphoid hyperplasia, l 6 follicular lymphoma, and even Hodgkin’s disease. For follicular lymphoma, the cells should be more monomorphic and tingible-body macrophages are scanty or absent. Immunohistochemistry will show a polytypic cell population in Castleman’s disease and monoclonality in lymphoma. The cytologic diagnosis of Hodgkin’s disease will depend on the finding of Reed-Sternberg cells and/or Hodgkin cells. Finally, a search for oncocytic cells and lymphoepithelial island is required to exclude Warthin’s tumor and lymphoepithelial lesion, respectively. Branchial cleft cysts are located in the anterolateral region of the neck. Those related to the first cleft appear in the preauricular area or beneath the posterior half of the mandible. Those related to the second cleft appear just anterior to the sternocleidomastoid muscle. Others are in the lower neck region. It is the cyst related to the first cleft defect that mimics parotid gland lesion. Like pilomatrixoma, it should not be diagnosed as well-differentiated squamous cell carcinoma. The squamous cells in branchial cyst are uniform and bland with fine nuclear chromatin o r pyknotic nuclei. The clinical detail in such a case is very important because branchial cleft cyst occurs in younger patients while squamous cell carcinoma occurs usually in older patients. In summary, we think it is important that one should recognise the mimickers of salivary gland lesions for three reasons. First, salivary gland neoplasm is uncommonly encountered in individual cytology practice which means that experience is difficult to accumulate. Second, in some centers where the surgeons or the oncologists perform the F N A , the pathologists may not know the exact site, plane, and consistency of the lesions which may affect the correct interpretation. I n these circumstances, the pathologist may try to fit the smear findings into that of primary of secondary salivary neoplasm as happened in our case 1 ‘‘315
’*
Fig. 4. Cytology smear of a brunchial cleft cyst (case 7) showing (A) mature squamous cells and (B) clump of lymphocytes (hematoxylin & rosin \lain, >~300).
phic adenoma’ and leiomyoma. Myxoid stroma is also present in pleomorphic adenoma. Thus the whole smear pattern should be taken into consideration in diagnosis. Furthermore, an enquiry into sensation of pain during aspiration is helpful as it is known that neurilemmoma may be painful to aspirate. Kimura’s disease is characterized by the presence of mature lymphocytes, eosinophils, vessels lined by plump endothelial cells, and fibrosis. 4-‘ Similar features can be encountered in angiolymphoid hyperplasia with eosinophilia (ALHE) which is considered a different entity because of different clinical presentation and histologic features. 4h The main histologic difference is that ALHE has exuberant angiomatoid proliferation and uncanalized masses of endothelial cells. Likewise in cytology smears, A L H E contains predominantly epithelioid endothelial cells and eosinophils. l o Another differential diagnosis to consider is healing abscess which sometimes yields many lymphocytes, eosinophils, and connective tissue, but it also contains plenty of polymorphs and histiocytes which are lacking in Kimura’s disease. 442
Diugnortic Cyroputhology, Val 8, No 5
CYTODIAGNOSIS OF SALIVARY GLAND SWELLINGS
and 3 where a pilomatrixoma and a neurilemmorna were diagnosed as pleomorphic adenoma. Last, the rnanagement of these rnirnickers may be quite different from that of primary salivary gland neoplasm. Usually only local excision is required and the salivary gland may be spared.
Acknowledgments We thank Dr. C. Hsu for reviewing the manuscript and Mrs. Prisica Cheng for typing the manuscript.
References I . KatL AD. Unusual lesions of the parotid gland. J Surg Oncol 1975;7: 2 1 9-23 5 . 2. Chan MKM, McGuire LJ. Fine needle aspiration cytodibgnosis of an unusual parotid mass. Acta Cytol (Baltimore) 1989;33:27&276. 3. Bondeson L, Lindholm K, Thorstenson S. Benign dermal eccrine cylindroma-a pitfall in the cytologic diagnosis of adenoid cystic carcinoma. Acta Cytol (Baltimore) 1983;27:326-328. 4. Kung ITM, Gibson JB, Bannatyne PM. Kimura’s disease: a clinicopathological study of 21 cases and its distinction from angiolymphoid hyperplasia with eosinophilia. Pathology 1984;16:2944. 5. Hui PK, Chan JK, Ng CS, et al. Lymphadenopathy of Kimura’s disease. Am J Surg Pathol 1989;13:177-186. 6. Chan JK, Hui PK, Ng CS, et al. Epithelioid haemangioma (angiolymphoid hyperplasia with eosinophilia) and Kimura’s disease in Chinese. Histopathology 1989; 15:557-574. 7. Woyke S, Olszewski W, Eichelkvault A. Pilomatrixoma-a pitfall in the aspiration cytology of skin tumors. Acta Cytol (Baltimore) 1982; 26: 189-194.
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