Fine-Needle Aspiration Diagnosis of High Grade Adenoid Cystic Carcinoma Metastatic to the Pancreas Doina David, M.D.,* Sreeharsha N. Masineni, M.D., and Tamar Giorgadze, M.D., Ph.D., M.I.A.C.

Pancreatic tumors are mostly primary tumors, with only rare metastatic tumors described in the literature. Here we report an unusual case of fine-needle aspiration (FNA) diagnosis of high grade adenoid cystic carcinoma of the parotid gland metastatic to the pancreas. The aspirate smears were moderately cellular and revealed numerous basaloid neoplastic cells. The cytomorphologic differential diagnosis included primary pancreatic tumor with small cell morphology as well as metastatic tumors. By immunocytochemistry, the tumor cells were positive for cytokeratins (AE1/AE3, CAM5.2, and CK7), and CD117 (C-KIT), and negative for CD45, WT1, synaptophysin, chromogranin, CD56, TTF-1, and CK20. The cytomorphologic features and immunoprofile in our case were consistent with high-grade carcinoma metastases from patient’s known salivary gland primary. To the best of our knowledge, this case is the first reported encounter of FNA diagnosis of pancreatic metastasis with small cell morphology from a salivary gland neoplasm as primary C V 2014 Wiley site. Diagn. Cytopathol. 2015;43:117–120. Periodicals, Inc.

Key Words: FNA; carcinoma

pancreas;

metastasis;

adenoid

cystic

Pancreatic tumors are mostly primary tumors, with only rare metastatic tumors described in the literature.1–6 However, one must rule out the possibility of a pancreatic metastasis for proper management. While metastatic tumors to the pancreas have been reported from a number of different sites, primary salivary gland tumor metastasis to the pancreas has not been previously described in the

Department of Pathology and Laboratory Medicine, Detroit Medical Center/Wayne State University School of Medicine, Detroit, Michigan *Correspondence to: Doina David, MD, 6071 West Outer Drive, Detroit, MI 48235, USA. E-mail: [email protected] Received 6 September 2013; Revised 30 December 2013; Accepted 21 January 2014 DOI: 10.1002/dc.23128 Published online 19 February 2014 in Wiley Online Library (wileyonlinelibrary.com). C 2014 WILEY PERIODICALS, INC. V

literature. Most prevalent primary sites of metastasis include kidney, lung, and skin melanoma.1–6 Here we report an unusual case of fine-needle aspiration (FNA) diagnosis of high grade adenoid cystic carcinoma of the parotid gland metastatic to the pancreas. A 65-year-old African-American woman was diagnosed with high grade adenoid cystic carcinoma of the left parotid gland for which she underwent left radical parotidectomy and neck dissection. Six months later she presented to the emergency room with a complaint of pain in the right upper quadrant and right flank. The patient was suspected to have acute pancreatitis and was admitted. Enhanced computed tomography (CT) scan of the abdomen was performed and revealed a 6.6 cm 3 5.8 cm 3 5.4 cm pancreatic head mass that was 18-fluoro-2deoxyglucose (FDG)--avid on positron-emission tomography scan. The radiologic differential diagnosis included a pancreatic adenocarcinoma or metastasis. A CT-guided FNA of the pancreatic head mass was performed. Both airdried and alcohol-fixed smears were prepared from each pass, and the needle was rinsed in CytoLyt fixative for cell block preparation. On-site evaluation of the air-dried DiffQuik (DQ)-stained smears confirmed the adequacy of the samples. The alcohol-fixed smears were stained with Papanicolaou stain (PAP). Immunocytochemical stains were performed on the cell block preparation slides in the presence of appropriate positive and negative controls. The aspirate smears were moderately cellular and revealed numerous basaloid neoplastic cells scattered singly and also present in groups. The cytoplasm was scant and the nuclei demonstrated significant anisonucleosis and nuclear membrane irregularities. Many of the tumor cells also showed crush artifact (Figs. 1 and 2). The diagnostic considerations and immunostains helpful for the differential diagnosis in our case are shown in Table I. The cytomorphologic differential diagnosis was broad and Diagnostic Cytopathology, Vol. 43, No 2

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Fig. 1. High power view showing tumor cells with scant cytoplasm, nuclear pleomorphism, and crush artifact (A, DQ stain, 403 objective; B, Papanicolaou stain, 403 objective).

Fig. 2. High power view with tumor cells showing nuclear overlapping, molding, and few with conspicuous nucleoli (A, DQ stain, 603 objective; B, Papanicolaou stain, 603 objective).

included primary pancreatic tumor with small cell morphology as well as metastatic tumors. Within this broad diagnostic spectrum, recognizing distinctive cytomorphologic features and application of immunocytochemistry will be instrumental to achieve an accurate diagnosis. A metastasis from small cell carcinoma as well as a primary pancreatic endocrine neoplasm is ruled out by immunonegativity for neuroendocrine markers and immunopositivity for CD117 (C-kit). A solid pseudopapillary neoplasm of pancreas will have cytomorphologic features such as pseudopapillary growth, and tumor cells exhibiting eosinophilic to clear or foamy cytoplasm and round to oval nuclei with stippled chromatin and characteristic frequent nuclear grooves. In addition, the tumor cells will show some immunopositivity for neuroendocrine markers (CD56, synaptophysin), immunoreactivity to CD10, and abnormal cytoplasmic and nuclear immunolabeling for Beta-catenin. The acinar cell carcinoma has 118

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cytomorphologic features such as singly scattered, loosely cohesive groups, and solid nest of cells with mild to moderate nuclear pleomorphism and prominent nucleoli. The cytoplasm of tumor cells is moderate to abundant, granular. Acinar formation and scant stroma may be also seen, and the tumor cells show immunopositivity for trypsin and alpha-1-antitrypsin. Lymphoma will have a distinctive discohesive cytomorphology with immunonegativity for cytokeratins and positive immunostaining for CD45. By immunocytochemistry, in our case the tumor cells were positive for cytokeratins (AE1/AE3, CAM5.2, and CK7), and CD117, and negative for CD45, WT1, synaptophysin, chromogranin, CD56, TTF-1, and CK20. The cytomorphologic features and immunoprofile of the current tumor were consistent with a high-grade carcinoma metastases from patient’s known salivary gland primary (Figs. 3A–D).

Diagnostic Cytopathology DOI 10.1002/dc

FNA DIAGNOSIS OF PANCREATIC METASTASIS Table I. Differential Diagnosis and Immunostaining Pattern Differential Diagnosis

Immunostain Keratin Chromogranin Synaptophysin CD56 CD10 CD45 Trypsinb Alpha-1-antitrypsin CD117 (C-KIT) Beta-catenin TTF-1

Adenoid cystic carcinoma 11 – – – – – – – 11 – –

Small cell carcinoma

Pancreatic endocrine neoplasm

Solid pseudopapillary neoplasm

Acinar cell Carcinoma

Lymphoma

11 11 11 11 – – – – – – 1/2

11 11 11 11 – – – 2/1 – – –

1/2 – 1 11 11 – – 1/2 – 11c –

11 – – – – – 11 1 – – –

– – – 2/1a 2/1a 11 – – – – –

1, often positive. 11, consistently positive. 2/1, may be negative. 1/2, may be positive. a depending on the type of lymphoma. b Also chymotrypsin. c Aberrant nuclear and cytoplasmic expression.

Fig. 3. A,B: Cell block preparation of the pancreatic FNA showing focal CD117 positivity, confirming metastatic adenoid cystic carcinoma (A, hematoxylin and eosin stain, 403 objective; B, CD117 immunostain, 403 objective). C, D: Surgical pathology specimen from salivary gland tumor showing solid adenoid cystic carcinoma showing diffuse CD117 immunopositivity, confirming the diagnosis (C, hematoxylin and eosin stain, 403 objective; D, CD117 immunostain, 403 objective). Diagnostic Cytopathology, Vol. 43, No 2

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Metastatic tumors to the pancreas overall are extremely rare, represent 2–11% of pancreatic malignancies. They may radiologically and clinically mimic primary pancreatic carcinoma.2 While metastases from various primary sites have been described, renal cell carcinoma, small cell lung carcinoma, and skin melanoma are the most common tumors metastasizing to the pancreas.2–6 The pancreatic head is reportedly the most common site of metastasis.4,5 Gilbert et al. have also found that in a significant subset of their cases (16%) a pancreatic mass was the first clinically recognized manifestation of an extrapancreatic malignancy.4 Metastases to the pancreas represent a diagnostic challenge also due to overlapping morphologic features with primary pancreatic tumors as well as other metastatic lesions of the pancreas. This is even more so for cytologic diagnosis of metastatic lesions to the pancreas. In our case, the differential diagnosis was broad and included basaloid and small cell tumors of the pancreas, both primary and metastatic. Most common reported metastatic sites of high grade adenoid cystic carcinoma include lungs, cervical lymph nodes, bones, liver, and brain.7 Small cell morphology is not a common presentation for high grade adenoid cystic carcinoma. Nevertheless, in cytology specimens metastasis from high grade adenoid cystic carcinoma may be easily confused with primary neoplasm with small cell morphology that may be encountered in the site of distant metastasis.8 Yu and Caraway suggested that this unusual presentation of adenoid cystic carcinoma that does occur in metastatic sites should be recognized as such in cytology specimens, thereby preventing a needless search for secondary primary malignancy.9 To the best of our knowledge, our case is the first reported encounter of

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FNA diagnosis of pancreatic metastasis with small cell morphology from a salivary gland neoplasm as primary site. Our case reiterates that knowing clinical history, obtaining adequate diagnostic material for ancillary studies, and comparing the morphology of the tumor with that of the patient’s known primary are key to the diagnosis of metastatic lesions to the pancreas.

References 1. Bernstein J, Adeniran AJ, Cai G, et al. Endoscopic ultrasoundguided fine-needle aspiration diagnosis of Merkel cell carcinoma metastatic to the pancreas. Diagn Cytopathol, doi: 10.1002/ dc.22884. 2. Elsheikh TM, Herzberg AJ, Silverman JF. Fine-needle aspiration cytology of metastatic malignancies involving unusual sites. Am J Clin Pathol 1997;108(4 Suppl 1):S12–S21. 3. Adsay NV, Andea A, Basturk O, Kilinc N, Nassar H, Cheng JD. Secondary tumors of the pancreas: An analysis of a surgical and autopsy database and review of the literature. Virchows Arch 2004; 444:527–535. 4. Gilbert CM, Monaco SE, Cooper ST, Khalbuss WE. Endoscopic ultrasound-guided fine-needle aspiration of metastases to the pancreas: A study of 25 cases. Cytojournal 2011;8:7. 5. Volmar KE, Jones CK, Xie HB. Metastases in the pancreas from nonhematologic neoplasms: Report of 20 cases evaluated by fineneedle aspiration. Diagn Cytopathol 2004;31:216–220. 6. Olson MT, Wakely PE, Jr, Ali SZ. Metastasis to the pancreas diagnosed by fine needle aspiration. Acta Cytol 2013;57:473–480. 7. Seethala RR, Hunt J, Baloch ZW, LiVolsi VA, Barns EL. Adenoid cystic carcinoma with high-grade transformation. A report of 11 cases and a review of the literature. Ann J Surg Pathol 2007;31: 1683–1694. 8. Anderson RJ, Johnston WW, Szpak CA. Fine needle aspiration of adenoid cystic carcinoma metastatic to the lung. Cytologic features and differential diagnosis. Acta Cytol 1985;29:527–532. 9. Yu GH and Caraway NP. Poorly-differentiated adenoid cystic carcinoma: Cytologic appearance in fine-needle aspirates of distant metastases. Diagn Cytopathol 1996;15:296–300.

Fine-needle aspiration diagnosis of high grade adenoid cystic carcinoma metastatic to the pancreas.

Pancreatic tumors are mostly primary tumors, with only rare metastatic tumors described in the literature. Here we report an unusual case of fine-need...
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