TIMELY REVIEW Section Editor: Liron Pantanowitz, M.D.
Pitfalls of Fine-Needle Aspiration Cytology of Parotid Membranous Basal Cell Adenoma—A Review of Pitfalls in FNA Cytology of Salivary Gland Neoplasms With Basaloid Cell Features Matthew Jurczyk, C.T. (A.S.C.P.), Joseph F. Peevey, M.D., Mark A. Vande Haar, C.T. (A.S.C.P.), and Xiaoqi Lin, M.D., P.hD*
Membranous basal cell adenoma (MBCA) is a rare benign salivary gland neoplasm. It is difficult to diagnose MBCA based on fine-needle aspiration (FNA) cytology due to rare reporting of its FNA cytology and overlapping of its FNA cytologic features with some benign and malignant entities. We present a case of MBCA in a 67-year-old female that was originally misinterpreted as adenoid cystic carcinoma (ACC) on FNA cytology. The FNA smears showed numerous uniform small basaloid epithelial cells with round or oval nuclei and inconspicuous nucleoli, and scant cytoplasm. The basaloid cells surround acellular, dense, homogenous material or are surrounded by acellular or paucicellular dense homogeneous material possibly containing bland spindle cells. The basaloid cells are present in variably sized three-dimensional clusters, acini, or sheets with variable cohesion. The dense homogenous material surrounded by basaloid cells may be interconnected. High power magnification reveals the homogeneous material to have a fibrillar texture. The edges of dense homogenous materials were welldemarcated. We describe the diagnostic pitfalls of FNA for MBCA, particularly versus ACC, basal cell adenoma, cellular pleomorphic adenoma, myoepithelioma, basal cell adenocarcinoma, and basaloid squamous cell carcinoma in hope of
Department of Pathology, Northwestern Memorial Hospital, Northwestern University, Chicago, Illinois *Correspondence to: Xiaoqi Lin, Department of Pathology, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern university, 251 E. Huron St., Galter Pavilion 7-132F, Chicago, IL 60611. E-mail: [email protected] Received 1 July 2014; Accepted 9 November 2014 DOI: 10.1002/dc.23234 Published online 27 November 2014 in Wiley Online Library (wileyonlinelibrary.com).
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improving clinical management and patient treatment. Diagn. Cytopathol. 2015;43:432–437. VC 2014 Wiley Periodicals, Inc. Key Words: membranous basal cell adenoma; parotid; fineneedle aspiration; adenoid cystic carcinoma
Basal cell adenoma (BCA) is a rare benign salivary gland neoplasm that was first described in 1967 and characterized by basaloid appearance of the tumor cells.1,2 It comprises only 1–3% of salivary gland tumors,2 and frequently occurs in the parotid (75%).1–3 Several variants have been reported, including trabecular, tubular, canalicular, solid, high cellularity of the stroma, and membranous (MBCA) forms.2,4 Macroscopically, MBCA tumors tend to be firm, well-circumscribed, encapsulated, cystic masses that are grossly white to gray in color.4,5 On histology MBCA shows monomorphous cells in pseudotubular arrangements within nests separated by hyalinized fibrous stroma. Round to polygonal eosinophilic cells bordered by palisading columnar cells may be seen. Mitotic figures are rare and the cytoplasm may be focally positive for mucicarmine. The tumor may be strongly PAS positive, but negative for amyloid.5 Both BCA and adenoid cystic carcinoma (ACC) were thought to arise from the same basal stem cell type.6 There are, however, important histologic differences in the vascular patterns of both tumors. BCA has a more distinct pattern with microencapsulated areas that are not apparent in ACC.7,8 BCA also displays a clear separation of epithelium from stroma C 2014 WILEY PERIODICALS, INC. V
Diagnostic Cytopathology DOI 10.1002/dc
PITFALLS OF FINE-NEEDLE ASPIRATION CYTOLOGY
that is neither present in ACC nor pleomorphic adenoma.7 The cribriform pattern typical of ACC is not often seen in MBCA.9 It is difficult to diagnose MBCA based on fine-needle aspiration (FNA) cytology due to rare reporting of its FNA cytology and overlapping of its FNA cytologic features with some benign and malignant entities. Given the rarity of MBCA and the challenge of using FNA cytology to render a definitive diagnosis,3,9,10 this topic merits further study and discussion. Our purpose is to describe the diagnostic pitfalls of FNA for MBCA, especially versus ACC, basal cell adenoma, cellular pleomorphic adenoma, metastatic basal cell carcinoma, metastatic basaloid squamous carcinoma, and myoepithelioma in hope of improving clinical management and patient treatment.
Case Presentation Clinical Findings The patient was a 67-year-old female, who had a past medical history of hypothyroidism, breast cancer, colon cancer, and vulvar melanoma, presented with an asymptomatic parotid mass for 1 year. Relating to the right parotid gland, computed tomography (CT) as well as positron emission tomography (PET) imaging revealed a 2.3 3 2.2 3 1.5 cm enhancing, lobulated right neck lesion with slightly ill-defined borders. No evidence of enlarged neck lymph nodes was identified. Given the patient’s clinical history, the differential diagnosis includes metastasis versus a primary parotid lesion. The patient was referred to NMH for subsequent FNA biopsy.
were well-demarcated (Figs. 1A–F, and H). Myoepithelial cells, marked atypia, mitotic figures, and necrosis was not observed. The cytologic interpretation was “Epithelial cell neoplasm, favoring an adenoid cystic carcinoma”.
Surgical Resection and Histopathology The patient then received a right parotidectomy. Serial sections revealed a 3 3 2.1 3 1.5 cm, lobulated, relatively well-circumscribed lesion with a tan cut surface. The tumor tissue was formalin fixed, paraffin embedded, sectioned, and stained with hematoxylin and eosin (H&E) stain. The sections showed that nests of basaloid cells were surrounded by hyalinized stroma or basaloid cells surrounded hyaline stroma (Figs. 1I and J). The vessel walls were also hyalinized (Figs. 1I and J). No invasion, atypia, or necrosis was seen. Immunohistochemical (IHC) stains for CD117 (Catalog # A4502, DakoCytomation, Carpinteria, CA), CD43 (Catalog # 760-2511, Ventana, Tucson, AZ), and Ki-67 (Catalog # 760-4286, DakoCytomation, Carpinteria, CA) were performed on the sections of paraffin-embedded surgical excisional specimens with appropriate positive and negative controls as previously described.11 The cutoff for positive staining is at least 5% of cells with moderate or strong intensity staining for IHC markers. The results showed that tumor cells are negative for CD117 and CD43 (data not shown). The proliferative index (Ki-67) is 5% (data not shown). The IHC results excluded adenoid cystic carcinoma. Based on the histomorphology and IHC results, a diagnosis of membranous basal cell adenoma was rendered.
Discussion Fine-Needle Aspiration Cytology Ultrasound-guided percutaneous FNA was performed with 25 gauge needles. The tissue sample from two passes was smeared on slides. One slide from each pass was air-dried and stained with Diff-Quik, and another slide was alcohol fixed and stained with Papanicolaou stain. Cytologic findings of the FNA smears revealed numerous uniform small basaloid epithelial cells with round or oval nuclei and inconspicuous nucleoli, and with scant cytoplasm (Figs. 1A–H). The basaloid cells surround acellular, dense, homogenous materials (Figs. 1A–C) or are surrounded by acellular or paucicellular dense homogeneous material possibly containing bland spindle cells or vessels inside (Figs. 1E and F), or present in small or larger, discohesive, or cohesive sheets or three-dimensional clusters (Figs. 1C, D, F and G), or acini (Figs. 1C and D). The homogeneous material which is surrounded by basaloid cells may be interconnected (1H). High power magnification might reveal that the dense homogeneous material have a fibrillar texture, which characteristically is not well appreciated in the photomicrographs due to image resolution. The edges of dense homogenous materials
This case posed significant diagnostic and clinical challenges due to past history of multiple primary malignancies. FNA cytology excluded metastatic malignancy, however, misinterpreted MBCA as ACC, illustrating that the two lesions share some cytologic features. MBCA has many mimics, making it one of the most challenging diagnoses in cytology. These mimics include ACC, pleomorphic adenoma (PA), myoepithelioma, conventional basal cell adenoma and its other variants (tubulotrabecular, solid), basal cell adenocarcinoma, dermal cylindromas, and basaloid squamous cell carcinoma.3,9,12 Misdiagnosis of BCA as ACC on FNA cytology do occur.3 Some authors even debated whether an FNA diagnosis for MBCA is practical.3,13 FNA smears of MBCA revealed numerous uniform small basaloid epithelial cells with round or oval nuclei and inconspicuous nucleoli, and with scant cytoplasm (Figs. 1A–H), which can also been seen in ACC (Figs. 2A–D), pleomorphic adenoma (PA) (Figs. 2E–H), and myoepithelioma (Figs. 2I–L) (Table 1). However, the cytoplasm of PA (Fig. 2F) myoepithelioma cells (Fig. 2K) may be moderate in amount and dense (Figs. 2F and K) and occasionally, myoepithelioma cells Diagnostic Cytopathology, Vol. 43, No 5
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Fig. 1. Fine-needle aspiration cytology and resected tissue histology of membranous basal cell adenoma. Figures 1A–H represent fine-needle aspiration cytology, 3600. Figures 1A, C, E, and G were stained with Diff-Quik stain, and Figures 1B, D, F, and H were stained with Papanicolaou stain. Figures 1I and J represent low power and high power fields of hematoxylin and eosin-stained resected tissue, 3200 and 3600, respectively.
Diagnostic Cytopathology DOI 10.1002/dc
PITFALLS OF FINE-NEEDLE ASPIRATION CYTOLOGY
Fig. 2. Fine-needle aspiration cytology of adenoid cystic adenoma (Figs. 2A–D), pleomorphic adenoma (Figs. 2E–H), and myoepithelioma (Figs. 2I–L). Figures 2B–D, F, G, J, and K were stained with Diff-Quik stain, 3600. Figures 2A, E, 1, and K were stained with Papanicolaou stain, 3600.
and myoepithelial cells in PA may show plasmacytoid features and spindle shaped nuclei, and possibly have conspicuous nucleoli,14 which can distinguish PA and myoepithelioma from MBCA and ACC. The cytologic feature of basaloid cells surrounding acellular, homogenous material (Figs. 1A–C) as seen in this case is a typical cytologic feature of ACC (Fig. 2A), which can also seen in PA (Fig. 2E) and myoepithelioma (Figs. 2I and J). This is the main pitfall resulting in misinterpreting MBCA, PA, and myoepithelioma as ACC. The acellular material seen in MBCA (Figs. 1A–C) was denser than that seen in ACC (Fig. 2A) which stains paler, and is similar to that seen in PA (Fig. 2E) and myoepithelioma (Figs. 2I and J). In addition, fibrous lines can be seen in the acellular material
of MBCA, PA, and myoepithelioma, but not in that of ACC which is mucoid and more homogenous. Small nuclei may be seen in the basaloid cell-surrounded material of PA (Fig. 2E). The cytologic feature that basaloid cells are surrounded by acellular or paucicellular, dense homogeneous material with or without bland spindle cells or vessels, as seen in this case (Figs. 1C and F)15 may also be seen in the PA (Fig. 2G) but is not seen in ACC. A key distinguishing feature of MBCA is the presence of basement material which can appear at the edge of tissue fragments.10 The cytologic feature that basaloid cells are present in variably sized three-dimensional clusters and variably cohesive sheets (Figs. 1C, D, F, and G), or acini (Figs. 1C and D) can also been seen in ACC (Figs. 2A, B, Diagnostic Cytopathology, Vol. 43, No 5
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JURCZYK ET AL. Table 1. Comparison of FNA Cytomorphologic Features of Membranous Basal Cell Adenoma (MBCA), Adenoid Cystic Carcinoma (ACC), Pleomorphic Adenoma (PA), Myoepithelioma, and Conventional Basal Cell Adenoma (BCA) Features
MBCA
ACC
Cells
Basaloid
Basaloid
Architectures
Basaloid cells surround HM Acini, sheets, 3-dimensional clusters of variable size and cohesion
Homogeneous Material (HM)
Basaloid cells surrounding HM Basaloid cells surrounded by HM Acini, sheets, 3-dimensional clusters of variable size and cohesion Dense Fibrillary texture Well-defined borders
Mitosis
No
Yes
Pale Mucoid/hyaline texture Well-defined borders
and D), PA (Figs. 2E–H), and myoepithelioma (Figs. 2I– L). The edges of metachromatic materials seen in MBCA were well-demarcated (Figs. 1A–F, and H), similar to those seen in ACC (Figs. 2A and C). However, the edges of the metachromatic material seen in the PA are vaguely feathery and have a fibrillar texture. There is often no chondroid matrix material in MBCA, ACC, and myoepithelioma, which is characteristic of PA. Nuclei may be seen in the metachromatic homogenous material (Fig. 2E). The presence of mitotic figures can also be used to distinguish between MBCA, PA or myoepithelioma and ACC or other malignant tumors which tend to have high mitotic counts.9 Overlapping features of the basement membrane in MBCA, ACC, PA, and myoepithelioma pose a diagnostic dilemma in cytology. However, the above cytologic features are useful to distinguish MBCA from ACC, PA, or myoepithelioma. MBCA may be cytologically difficult to be distinguished from conventional and other variants of BCA. Prominent paucicellular hyalinized stroma present in the FNA smears may be the key features to distinguish MBCA from conventional and other variants of BCAs. Regardless, from a clinical management point of view, it is not necessary to distinguish MBCA from conventional and other variants of BCA. FNA challenges have many pitfalls when distinguishing MBCA from basal cell adenocarcinoma and basaloid squamous cell carcinoma. FNA smears of the solid subtype of basal cell adenocarcinoma contain cohesive but haphazardly organized clusters of basaloid cells, whereas the architecture in MBCA shows groups of cells surrounded by a distinct peripheral band of hyalinized stroma.16 It is important to note that most basal cell adenocarcinomas are microscopically identical to BCAs except for the presence of an invasive histologic growth pattern and FNA cannot 436
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PA Basaloid, Ductal, myoepithelial, fibroblasts, others (eg. chondroid, etc.) Basaloid cells surrounding HM Basaloid cells surrounded by HM Acini, 3-dimensional clusters of variable size and cohesive Dense Fibrillary texture Myxofibrous or chondroid texture Poorly-defined borders Possibly containing nuclei No
Myoepithelioma
BCA
Basaloid, spindle, plasmacytoid, clear, oncocytic
Basaloid
Basaloid cells surrounding HM Acini, 3-dimensional clusters of variable size and cohesive
Acini, 3-dimensional cohesive clusters
Variable Fibrillary texture Myxoid texture Rarely lipomatous
Variable Fibrillary texture Myxoid texture
No
No
often detect parenchymal invasion, Therefore, basal cell adenomas and basal cell adenocarcinomas are difficult to distinguish by FNA.15 Cytologic atypia, mitotic activity, and necrosis may be useful to distinguish MBCA from basal cell adenocarcinoma and basaloid squamous cell carcinoma. Peripheral nuclear palisading is seen in basal cell carcinoma and basaloid squamous cell carcinoma, but not in BCA. The examination of the skin or oral mucosa is also useful to exclude these skin or oral mucosa neoplasms involving salivary glands. MBCA is the most cytologically and histologically distinct of the three subtypes of BCA due to its occasional association and histological resemblance to dermal cylindromas, trichoepitheliomas, and spiradenomas.17,18 MBCA microscopically displays epithelial nests surrounded by deposition of basal lamina, therefore, it has been referred to as “dermal analogue tumor”. Lesional location is important to distinguish MBCA from those dermal analogues, in the salivary glands versus in the dermis. In conclusion, careful attention must be given to all salivary gland cytology diagnostic pitfalls, especially those involving the differential diagnosis between MBCA and ACC. The approach to evaluate the FNA cytology of salivary gland lesions with basaloid cells is to recognize basaloid cells, presence of other types of cells, cell arrangement patterns, acellular globule quality, and stromal components. Although surgical resection is the advised plan of treatment for both MBCA and ACC, there are differences in the degree of dissection required and in instances when a core biopsy diagnosis may not be feasible prior to surgery and FNA cytology may be the only presurgical diagnostic option. Advancements in the science and art of salivary gland FNA cytology can be an invaluable tool to help clinicians better assess treatment options (such as facial nerve sparing surgery), resulting in improved patient care.
Diagnostic Cytopathology DOI 10.1002/dc
PITFALLS OF FINE-NEEDLE ASPIRATION CYTOLOGY
References 1. Kleinsasser O, Klein HJ. Basal cell adenoma of the salivary glands. Arch Klin Exp Ohren Nasen Kehlkopfheilkd 1967;189:302–316. 2. de Araujo VC. Basal cell adenoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World Health Organization Classification of Tumours: Pathology & Genetics - Head and Neck Tumours. Lyon: IARC Press; 2005. p 261–262. 3. Gupta N, Bal A, Gupta AK, Rajwanshi A. Basal cell adenoma: A diagnostic dilemma on fine needle aspiration cytology. Diagn Cytopathol 2011;39:913–916. 4. Headington JT, Batsakis JG, Beals TF, Campbell TE, Simmons JL, Stone WD. Membranous basal cell adenoma of parotid gland, dermal cylindromas, and trichoepitheliomas. Comparative histochemistry and ultrastructure. Cancer 1977;39:2460–2469. 5. Triest WE, Fried MP, Stanievich JF. Membranous basal cell adenoma of the hypopharynx. Arch Otolaryngol 1983;109:774–777. 6. Jao W, Keh PC, Swerdlow MA. Ultrastructure of the basal cell adenoma of parotid gland. Cancer 1976;37:1322–1333. 7. Bernacki EG, Batsakis JG, Johns ME. Basal cell adenoma. Distinctive tumor of salivary glands. Arch Otolaryngol 1974;99:84–87. 8. Christ TF, Crocker D. Basal cell adenoma of minor salivary gland origin. Cancer 1972;30:214–219. 9. Scott AR, Faquin WC, Deschler DG. Parotid mass in a woman with multiple cutaneous cylindromas. Head Neck 2010;32:684–687. 10. Galed-Placed I, Yebra-Pimentel MT. Synchronous, double parotid tumor: Fine needle aspiration cytology diagnosis of the membra-
nous basal cell adenoma component. Acta Cytol 2000;44:1120– 1122. 11. Zhu B, Lin X. Immunoprofile of mucinous non-neoplastic cyst of the pancreas. Appl Immunohistochem Mol Morphol 2013;21:265– 270. 12. Lopez JI, Ballestin C. Fine-needle aspiration cytology of a membranous basal cell adenoma arising in an intraparotid lymph node. Diagn Cytopathol 1993;9:668–672. 13. Hood IC, Qizilbash AH, Salama SS, Alexopoulou I. Basal-cell adenoma of parotid. Difficulty of differentiation from adenoid cystic carcinoma on aspiration biopsy. Acta Cytol 1983;27:515–520. 14. Crumpler C, Scharfenberg JC, Reed RJ. Monomorphic adenomas of salivary glands. Trabecular-tubular, canalicular, and basaloid variants. Cancer 1976;38:193–200. 15. Geisinger KR, Stanley MW, Raab SS, Silverman JF, Abati A. Salivary gland masses. In: Geisinger KR, Stanley MW, Raab SS, Silverman JF, Abati A, editors. Modern Cytopathology. Crchill Livingstone: Elsevier Science; 2003. p 781–811. 16. Faquin WC, Powers C. Basaloid tumors: Basal cell adenoma and basal cell adenocarcinoma. In: Faquin WC, Powers C, editors. Salivary Gland Cytopathology. Verlag: Springer; 2008. p 115–130. 17. Zarbo RJ. Salivary gland neoplasia: A review for the practicing pathologist. Mod Pathol 2002;15:298–323. 18. Kazakov DV, Benkova K, Michal M, Vanecek T, Kacerovska D, Skalova A. Skin type spiradenoma of the parotid gland with malignant transformation: report of a case with analysis of the CYLD gene. Hum Pathol 2009;40:1499–1503.
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Pitfalls of Fine-Needle Aspiration Cytology of Parotid Membranous Basal Cell Adenoma—A Review of Pitfalls in FNA Cytology of Salivary Gland Neoplasms With Basaloid Cell Features Matthew Jurczyk, C.T. (A.S.C.P.), Joseph F. Peevey, M.D., Mark A. Vande Haar, C.T. (A.S.C.P.), and Xiaoqi Lin, M.D., P.hD*
Membranous basal cell adenoma (MBCA) is a rare benign salivary gland neoplasm. It is difficult to diagnose MBCA based on fine-needle aspiration (FNA) cytology due to rare reporting of its FNA cytology and overlapping of its FNA cytologic features with some benign and malignant entities. We present a case of MBCA in a 67-year-old female that was originally misinterpreted as adenoid cystic carcinoma (ACC) on FNA cytology. The FNA smears showed numerous uniform small basaloid epithelial cells with round or oval nuclei and inconspicuous nucleoli, and scant cytoplasm. The basaloid cells surround acellular, dense, homogenous material or are surrounded by acellular or paucicellular dense homogeneous material possibly containing bland spindle cells. The basaloid cells are present in variably sized three-dimensional clusters, acini, or sheets with variable cohesion. The dense homogenous material surrounded by basaloid cells may be interconnected. High power magnification reveals the homogeneous material to have a fibrillar texture. The edges of dense homogenous materials were welldemarcated. We describe the diagnostic pitfalls of FNA for MBCA, particularly versus ACC, basal cell adenoma, cellular pleomorphic adenoma, myoepithelioma, basal cell adenocarcinoma, and basaloid squamous cell carcinoma in hope of
Department of Pathology, Northwestern Memorial Hospital, Northwestern University, Chicago, Illinois *Correspondence to: Xiaoqi Lin, Department of Pathology, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern university, 251 E. Huron St., Galter Pavilion 7-132F, Chicago, IL 60611. E-mail: [email protected] Received 1 July 2014; Accepted 9 November 2014 DOI: 10.1002/dc.23234 Published online 27 November 2014 in Wiley Online Library (wileyonlinelibrary.com).
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improving clinical management and patient treatment. Diagn. Cytopathol. 2015;43:432–437. VC 2014 Wiley Periodicals, Inc. Key Words: membranous basal cell adenoma; parotid; fineneedle aspiration; adenoid cystic carcinoma
Basal cell adenoma (BCA) is a rare benign salivary gland neoplasm that was first described in 1967 and characterized by basaloid appearance of the tumor cells.1,2 It comprises only 1–3% of salivary gland tumors,2 and frequently occurs in the parotid (75%).1–3 Several variants have been reported, including trabecular, tubular, canalicular, solid, high cellularity of the stroma, and membranous (MBCA) forms.2,4 Macroscopically, MBCA tumors tend to be firm, well-circumscribed, encapsulated, cystic masses that are grossly white to gray in color.4,5 On histology MBCA shows monomorphous cells in pseudotubular arrangements within nests separated by hyalinized fibrous stroma. Round to polygonal eosinophilic cells bordered by palisading columnar cells may be seen. Mitotic figures are rare and the cytoplasm may be focally positive for mucicarmine. The tumor may be strongly PAS positive, but negative for amyloid.5 Both BCA and adenoid cystic carcinoma (ACC) were thought to arise from the same basal stem cell type.6 There are, however, important histologic differences in the vascular patterns of both tumors. BCA has a more distinct pattern with microencapsulated areas that are not apparent in ACC.7,8 BCA also displays a clear separation of epithelium from stroma C 2014 WILEY PERIODICALS, INC. V
Diagnostic Cytopathology DOI 10.1002/dc
PITFALLS OF FINE-NEEDLE ASPIRATION CYTOLOGY
that is neither present in ACC nor pleomorphic adenoma.7 The cribriform pattern typical of ACC is not often seen in MBCA.9 It is difficult to diagnose MBCA based on fine-needle aspiration (FNA) cytology due to rare reporting of its FNA cytology and overlapping of its FNA cytologic features with some benign and malignant entities. Given the rarity of MBCA and the challenge of using FNA cytology to render a definitive diagnosis,3,9,10 this topic merits further study and discussion. Our purpose is to describe the diagnostic pitfalls of FNA for MBCA, especially versus ACC, basal cell adenoma, cellular pleomorphic adenoma, metastatic basal cell carcinoma, metastatic basaloid squamous carcinoma, and myoepithelioma in hope of improving clinical management and patient treatment.
Case Presentation Clinical Findings The patient was a 67-year-old female, who had a past medical history of hypothyroidism, breast cancer, colon cancer, and vulvar melanoma, presented with an asymptomatic parotid mass for 1 year. Relating to the right parotid gland, computed tomography (CT) as well as positron emission tomography (PET) imaging revealed a 2.3 3 2.2 3 1.5 cm enhancing, lobulated right neck lesion with slightly ill-defined borders. No evidence of enlarged neck lymph nodes was identified. Given the patient’s clinical history, the differential diagnosis includes metastasis versus a primary parotid lesion. The patient was referred to NMH for subsequent FNA biopsy.
were well-demarcated (Figs. 1A–F, and H). Myoepithelial cells, marked atypia, mitotic figures, and necrosis was not observed. The cytologic interpretation was “Epithelial cell neoplasm, favoring an adenoid cystic carcinoma”.
Surgical Resection and Histopathology The patient then received a right parotidectomy. Serial sections revealed a 3 3 2.1 3 1.5 cm, lobulated, relatively well-circumscribed lesion with a tan cut surface. The tumor tissue was formalin fixed, paraffin embedded, sectioned, and stained with hematoxylin and eosin (H&E) stain. The sections showed that nests of basaloid cells were surrounded by hyalinized stroma or basaloid cells surrounded hyaline stroma (Figs. 1I and J). The vessel walls were also hyalinized (Figs. 1I and J). No invasion, atypia, or necrosis was seen. Immunohistochemical (IHC) stains for CD117 (Catalog # A4502, DakoCytomation, Carpinteria, CA), CD43 (Catalog # 760-2511, Ventana, Tucson, AZ), and Ki-67 (Catalog # 760-4286, DakoCytomation, Carpinteria, CA) were performed on the sections of paraffin-embedded surgical excisional specimens with appropriate positive and negative controls as previously described.11 The cutoff for positive staining is at least 5% of cells with moderate or strong intensity staining for IHC markers. The results showed that tumor cells are negative for CD117 and CD43 (data not shown). The proliferative index (Ki-67) is 5% (data not shown). The IHC results excluded adenoid cystic carcinoma. Based on the histomorphology and IHC results, a diagnosis of membranous basal cell adenoma was rendered.
Discussion Fine-Needle Aspiration Cytology Ultrasound-guided percutaneous FNA was performed with 25 gauge needles. The tissue sample from two passes was smeared on slides. One slide from each pass was air-dried and stained with Diff-Quik, and another slide was alcohol fixed and stained with Papanicolaou stain. Cytologic findings of the FNA smears revealed numerous uniform small basaloid epithelial cells with round or oval nuclei and inconspicuous nucleoli, and with scant cytoplasm (Figs. 1A–H). The basaloid cells surround acellular, dense, homogenous materials (Figs. 1A–C) or are surrounded by acellular or paucicellular dense homogeneous material possibly containing bland spindle cells or vessels inside (Figs. 1E and F), or present in small or larger, discohesive, or cohesive sheets or three-dimensional clusters (Figs. 1C, D, F and G), or acini (Figs. 1C and D). The homogeneous material which is surrounded by basaloid cells may be interconnected (1H). High power magnification might reveal that the dense homogeneous material have a fibrillar texture, which characteristically is not well appreciated in the photomicrographs due to image resolution. The edges of dense homogenous materials
This case posed significant diagnostic and clinical challenges due to past history of multiple primary malignancies. FNA cytology excluded metastatic malignancy, however, misinterpreted MBCA as ACC, illustrating that the two lesions share some cytologic features. MBCA has many mimics, making it one of the most challenging diagnoses in cytology. These mimics include ACC, pleomorphic adenoma (PA), myoepithelioma, conventional basal cell adenoma and its other variants (tubulotrabecular, solid), basal cell adenocarcinoma, dermal cylindromas, and basaloid squamous cell carcinoma.3,9,12 Misdiagnosis of BCA as ACC on FNA cytology do occur.3 Some authors even debated whether an FNA diagnosis for MBCA is practical.3,13 FNA smears of MBCA revealed numerous uniform small basaloid epithelial cells with round or oval nuclei and inconspicuous nucleoli, and with scant cytoplasm (Figs. 1A–H), which can also been seen in ACC (Figs. 2A–D), pleomorphic adenoma (PA) (Figs. 2E–H), and myoepithelioma (Figs. 2I–L) (Table 1). However, the cytoplasm of PA (Fig. 2F) myoepithelioma cells (Fig. 2K) may be moderate in amount and dense (Figs. 2F and K) and occasionally, myoepithelioma cells Diagnostic Cytopathology, Vol. 43, No 5
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Fig. 1. Fine-needle aspiration cytology and resected tissue histology of membranous basal cell adenoma. Figures 1A–H represent fine-needle aspiration cytology, 3600. Figures 1A, C, E, and G were stained with Diff-Quik stain, and Figures 1B, D, F, and H were stained with Papanicolaou stain. Figures 1I and J represent low power and high power fields of hematoxylin and eosin-stained resected tissue, 3200 and 3600, respectively.
Diagnostic Cytopathology DOI 10.1002/dc
PITFALLS OF FINE-NEEDLE ASPIRATION CYTOLOGY
Fig. 2. Fine-needle aspiration cytology of adenoid cystic adenoma (Figs. 2A–D), pleomorphic adenoma (Figs. 2E–H), and myoepithelioma (Figs. 2I–L). Figures 2B–D, F, G, J, and K were stained with Diff-Quik stain, 3600. Figures 2A, E, 1, and K were stained with Papanicolaou stain, 3600.
and myoepithelial cells in PA may show plasmacytoid features and spindle shaped nuclei, and possibly have conspicuous nucleoli,14 which can distinguish PA and myoepithelioma from MBCA and ACC. The cytologic feature of basaloid cells surrounding acellular, homogenous material (Figs. 1A–C) as seen in this case is a typical cytologic feature of ACC (Fig. 2A), which can also seen in PA (Fig. 2E) and myoepithelioma (Figs. 2I and J). This is the main pitfall resulting in misinterpreting MBCA, PA, and myoepithelioma as ACC. The acellular material seen in MBCA (Figs. 1A–C) was denser than that seen in ACC (Fig. 2A) which stains paler, and is similar to that seen in PA (Fig. 2E) and myoepithelioma (Figs. 2I and J). In addition, fibrous lines can be seen in the acellular material
of MBCA, PA, and myoepithelioma, but not in that of ACC which is mucoid and more homogenous. Small nuclei may be seen in the basaloid cell-surrounded material of PA (Fig. 2E). The cytologic feature that basaloid cells are surrounded by acellular or paucicellular, dense homogeneous material with or without bland spindle cells or vessels, as seen in this case (Figs. 1C and F)15 may also be seen in the PA (Fig. 2G) but is not seen in ACC. A key distinguishing feature of MBCA is the presence of basement material which can appear at the edge of tissue fragments.10 The cytologic feature that basaloid cells are present in variably sized three-dimensional clusters and variably cohesive sheets (Figs. 1C, D, F, and G), or acini (Figs. 1C and D) can also been seen in ACC (Figs. 2A, B, Diagnostic Cytopathology, Vol. 43, No 5
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Diagnostic Cytopathology DOI 10.1002/dc
JURCZYK ET AL. Table 1. Comparison of FNA Cytomorphologic Features of Membranous Basal Cell Adenoma (MBCA), Adenoid Cystic Carcinoma (ACC), Pleomorphic Adenoma (PA), Myoepithelioma, and Conventional Basal Cell Adenoma (BCA) Features
MBCA
ACC
Cells
Basaloid
Basaloid
Architectures
Basaloid cells surround HM Acini, sheets, 3-dimensional clusters of variable size and cohesion
Homogeneous Material (HM)
Basaloid cells surrounding HM Basaloid cells surrounded by HM Acini, sheets, 3-dimensional clusters of variable size and cohesion Dense Fibrillary texture Well-defined borders
Mitosis
No
Yes
Pale Mucoid/hyaline texture Well-defined borders
and D), PA (Figs. 2E–H), and myoepithelioma (Figs. 2I– L). The edges of metachromatic materials seen in MBCA were well-demarcated (Figs. 1A–F, and H), similar to those seen in ACC (Figs. 2A and C). However, the edges of the metachromatic material seen in the PA are vaguely feathery and have a fibrillar texture. There is often no chondroid matrix material in MBCA, ACC, and myoepithelioma, which is characteristic of PA. Nuclei may be seen in the metachromatic homogenous material (Fig. 2E). The presence of mitotic figures can also be used to distinguish between MBCA, PA or myoepithelioma and ACC or other malignant tumors which tend to have high mitotic counts.9 Overlapping features of the basement membrane in MBCA, ACC, PA, and myoepithelioma pose a diagnostic dilemma in cytology. However, the above cytologic features are useful to distinguish MBCA from ACC, PA, or myoepithelioma. MBCA may be cytologically difficult to be distinguished from conventional and other variants of BCA. Prominent paucicellular hyalinized stroma present in the FNA smears may be the key features to distinguish MBCA from conventional and other variants of BCAs. Regardless, from a clinical management point of view, it is not necessary to distinguish MBCA from conventional and other variants of BCA. FNA challenges have many pitfalls when distinguishing MBCA from basal cell adenocarcinoma and basaloid squamous cell carcinoma. FNA smears of the solid subtype of basal cell adenocarcinoma contain cohesive but haphazardly organized clusters of basaloid cells, whereas the architecture in MBCA shows groups of cells surrounded by a distinct peripheral band of hyalinized stroma.16 It is important to note that most basal cell adenocarcinomas are microscopically identical to BCAs except for the presence of an invasive histologic growth pattern and FNA cannot 436
Diagnostic Cytopathology, Vol. 43, No 5
PA Basaloid, Ductal, myoepithelial, fibroblasts, others (eg. chondroid, etc.) Basaloid cells surrounding HM Basaloid cells surrounded by HM Acini, 3-dimensional clusters of variable size and cohesive Dense Fibrillary texture Myxofibrous or chondroid texture Poorly-defined borders Possibly containing nuclei No
Myoepithelioma
BCA
Basaloid, spindle, plasmacytoid, clear, oncocytic
Basaloid
Basaloid cells surrounding HM Acini, 3-dimensional clusters of variable size and cohesive
Acini, 3-dimensional cohesive clusters
Variable Fibrillary texture Myxoid texture Rarely lipomatous
Variable Fibrillary texture Myxoid texture
No
No
often detect parenchymal invasion, Therefore, basal cell adenomas and basal cell adenocarcinomas are difficult to distinguish by FNA.15 Cytologic atypia, mitotic activity, and necrosis may be useful to distinguish MBCA from basal cell adenocarcinoma and basaloid squamous cell carcinoma. Peripheral nuclear palisading is seen in basal cell carcinoma and basaloid squamous cell carcinoma, but not in BCA. The examination of the skin or oral mucosa is also useful to exclude these skin or oral mucosa neoplasms involving salivary glands. MBCA is the most cytologically and histologically distinct of the three subtypes of BCA due to its occasional association and histological resemblance to dermal cylindromas, trichoepitheliomas, and spiradenomas.17,18 MBCA microscopically displays epithelial nests surrounded by deposition of basal lamina, therefore, it has been referred to as “dermal analogue tumor”. Lesional location is important to distinguish MBCA from those dermal analogues, in the salivary glands versus in the dermis. In conclusion, careful attention must be given to all salivary gland cytology diagnostic pitfalls, especially those involving the differential diagnosis between MBCA and ACC. The approach to evaluate the FNA cytology of salivary gland lesions with basaloid cells is to recognize basaloid cells, presence of other types of cells, cell arrangement patterns, acellular globule quality, and stromal components. Although surgical resection is the advised plan of treatment for both MBCA and ACC, there are differences in the degree of dissection required and in instances when a core biopsy diagnosis may not be feasible prior to surgery and FNA cytology may be the only presurgical diagnostic option. Advancements in the science and art of salivary gland FNA cytology can be an invaluable tool to help clinicians better assess treatment options (such as facial nerve sparing surgery), resulting in improved patient care.
Diagnostic Cytopathology DOI 10.1002/dc
PITFALLS OF FINE-NEEDLE ASPIRATION CYTOLOGY
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