Occult primary parotid gland acinic cell adenocarcinoma presenting with extensive lung metastasis.
Abstract: Acinic cell adenocarcinoma is a malignant salivary gland neoplasm with a relatively low rate of lymphangitic spread to regional lymph nodes. Distant metastases are rare and their occurrence typically indicates an unfavorable outcome. We encountered an unusual example of acinic cell adenocarcinoma that initially presented in the lung, whereas the primary parotid carcinoma, despite extensive clinical evaluation, only became apparent 1 year after initial diagnosis. The histologic, immunohistochemical, and ultra-structural features of the tumor in the parotid gland and lung were similar. The tumor displayed an aggressive behavior resulting in death within 2 years of the initial presentation. This presentation is unique, showing that peripheral lung tumors of salivary gland type are likely to be metastatic, and careful clinical evaluation is warranted in establishing their primary site of origin.

(Arch Pathol Lab Med. 2007;131:970-973)
Article Type: Case study
Subject: Immunohistochemistry (Usage)
Lung cancer (Risk factors)
Lung cancer (Diagnosis)
Lung cancer (Case studies)
Salivary gland tumors (Diagnosis)
Salivary gland tumors (Care and treatment)
Salivary gland tumors (Development and progression)
Salivary gland tumors (Case studies)
Authors: Tavora, Fabio
Rassaei, Negar
Shilo, Konstantin
Foss, Robert D.
Galvin, Jeffrey R.
Travis, William D.
Franks, Teri J.
Pub Date: 06/01/2007
Publication: Name: Archives of Pathology & Laboratory Medicine Publisher: College of American Pathologists Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2007 College of American Pathologists ISSN: 1543-2165
Issue: Date: June, 2007 Source Volume: 131 Source Issue: 6
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 230247039
Full Text: Acinic cell adenocarcinoma (ACA) is generally considered a low-grade malignant tumor of salivary gland with low propensity for recurrences and metastases. (1) Metastases tend to occur after extended latency periods and are usually confined to the regional lymph nodes. Distant metastases are associated with poor prognosis and are generally preceded by local disease. (1,2) We describe a previously unreported occurrence, in which the patient presented with extensive lung metastases 1 year prior to the discovery of an occult primary parotid gland ACA.


A 65-year-old physically active woman presented with chest pain, malaise, and low-grade fever. The chest radiograph revealed a 2.8-cm mass in the base of the left lung, which rapidly evolved in the following months. Subsequent chest computed tomography scan confirmed the presence of multiple nodules involving the lower portion of the left lung (Figure, A). Thoracoscopic biopsy was diagnosed as ACA. The tumor was suspected to be metastatic from an occult salivary gland primary. However, extensive clinical and radiologic evaluation, including head and neck computed tomography, yielded no other primary site, and the patient underwent left extrapleural pneumonectomy. Her postoperative course was uneventful. A year later, she presented with facial pain. A 3-cm left parapharyngeal mass was discovered on computed tomography. The tumor involved the base of the skull as well as the facial nerve. A left parotidectomy was performed and revealed ACA that was histologically similar to the thoracic tumor. Postoperatively, the patient received a total radiation therapy dose of 60 Gy to the left neck and 40 Gy to the left hemithorax. Six months later, the patient presented with metastasis to cervical vertebra followed by multiple bone metastases to the calvarium. She received additional palliative radiation. The patient died 2 years after the initial presentation. No autopsy was performed.


The thoracoscopic biopsy, pneumonectomy specimen, and parotid gland resection were available for review. Commercially available antibodies against AE1/AE3 (1:400; Dako, Carpinteria, Calif), cytokeratin (CK) 7 (1:400;Dako), CK20 (1:200;Dako), carcinoembryonic antigen (polyclonal, 1:600; Dako), S100 (1:600; Dako), a1-antitrypsin (1:100; Dako), and thyroid transcription factor 1 (predilute solution; Cell Marque, Hot Springs, Ark) were applied to further characterize the tumors. Immunohistochemical studies were performed on representative deparaffinized slides using an automated slide stainer (Ventana benchmark, Ventana Medical Systems, Tucson, Ariz). Ultrastructural examination was carried out on a transmission electron microscope (Zeiss 109, Carl Zeiss SMT AG, Oberkochen, Germany).


Thoracic Tumor

The extrapleural pneumonectomy specimen demonstrated multiple tumor nodules involving the lung parenchyma in a peripheral pattern and invading the pleura, with extensive involvement of the visceral and parietal pleura and pericardium by tumor. There was involvement of hilar lymph nodes. The cut surface of the tumor was white-tan with geographic areas of necrosis and hemorrhage (Figure, B). The tumor was composed of large polygonal cells with abundant basophilic granular cytoplasm (Figure, C). Areas of cytoplasmic clearing and smaller cuboidal cells with increased nuclear-cytoplasmic ratio, vesicular nuclei, and prominent nucleoli were present. Occasional mitoses were seen. The tumor cells were arranged in solid sheets and lobules separated by delicate fibrovascular septae. A solid growth pattern predominated in the tumor, with scattered microcystic foci, characterized by small irregular cysts and vacuolated cells, present.


Parotid Tumor

The parotid gland resection specimen revealed a 3.2-cm infiltrative tumor located in the deep parotid gland lobe with invasion of the facial nerve and the base of skull. Microscopically, the tumor was multinodular and surrounded by a dense collagenous stroma. There was extensive infiltration of adjacent soft tissue. The tumor cell composition was similar to the lung tumor; however, it showed more conspicuous acinar cell differentiation and microcystic architecture. There was no evidence of transformation to a high-grade tumor (dedifferentiation).

Histochemical, Immunohistochemical, and Ultrastructural Findings

Periodic acid-Schiff with diastase stain highlighted the cytoplasmic secretory granules (Figure, D). No intracytoplasmic mucin was identified. Tumor cells in both sites were immunoreactive with low-molecular-weight keratin and carcinoembryonic antigen; weakly immunoreactive with S100, AE1/AE3, and a1-antitrypsin; and negative for CK7, CK20, and thyroid transcription factor 1. Acinar cells demonstrated conspicuous electron-dense cytoplasmic secretory granules on ultrastructural examination (Figure, E).


Acinic cell adenocarcinoma is a malignant tumor that shows differentiation toward serous acinar cells. (3) It is the third most common malignant salivary gland tumor after mucoepidermoid carcinoma and adenocarcinoma, not otherwise specified, and comprises approximately 10% of primary malignant salivary gland tumors. (4) Acinic cell adenocarcinoma typically displays a relatively indolent clinical course; however, in a small percentage of cases, recurrences and metastases occur, and these cases contribute to overall survival rates that are comparable to the survival rates of mucoepidermoid carcinoma. When the deep lobe of the parotid is affected, local recurrences (72%) and unfavorable outcomes (43%) are higher than in superficial tumors (18% and 9%, respectively). (5) If metastases occur, they are most commonly confined to the cervical lymph nodes. (1) Distant metastases signify a poor prognosis with death occurring within months of detection. Among distant metastases, bone and lung are the most common sites. (1,3,5,6) Metastasis from a salivary gland tumor in the absence of a clinically evident mass is an extremely uncommon event. In all reported cases of primary ACA of the salivary gland with distant metastases, the primary tumor was diagnosed first and was followed by local recurrences and/or local lymph node involvement before the presentation of distant metastases. To the best of our knowledge, our case is unique in its presentation in which the distant lung metastases occurred 1 year prior to the discovery of the primary parotid ACA.

Very few cases of primary salivary gland ACA with lung metastases are documented in the literature. (7-9) Hynes et al (10) reported a case with pleural encasement by metastatic ACA. In all these case reports, the pulmonary metastases occurred 5 to 30 years after the primary diagnosis. In 1 series of primary salivary gland tumors, (2) local recurrences preceded distant metastases in all cases of ACA. The Table summarizes the frequency of distant metastases based on the data from recent series.

Primary pulmonary ACA, also known as the Fechner tumor, is rare with only 11 cases described in the literature. (11-14) In at least 2 cases, there were regional lymph node metastases (13,14) in a pattern typical of a primary lung adenocarcinoma. The largest series to date describes 5 cases of primary pulmonary ACA showing relatively indolent behavior and favorable prognosis. (11) Histologically, immunohistochemically, and ultrastructurally, these tumors are similar to primary salivary gland ACA, making their separation from metastases dependent on radiologic and clinical findings.

In a small proportion of primary salivary gland ACA, bilateral tumors are present. (3) It could be argued that the lung and parotid tumors in our case are metachronous primaries. Although this possibility cannot be completely excluded, the pattern of metastasis in our case is compatible with that observed in primary salivary gland ACA, thus metachronous tumors seem unlikely. Our case is also interesting in light of the newly emerging concept of tumor metastasis that suggests the presence of an early latent disseminated stage. (15) According to this view, the disseminated tumor cells are present early in the course of tumor progression and the acquisition of additional genetic aberrations signifies clinically apparent disease at the metastatic sites. It is plausible to hypothesize that in the presented case the lung became a site of the latent metastasis from an occult parotid carcinoma, with both tumors in the lung and parotid undergoing malignant transformation at a different pace.

In conclusion, this case highlights a rare manifestation of primary parotid gland ACA metastatic to the lung and emphasizes that the ACA encountered in the periphery of lung or involving pleura is likely to be metastatic from salivary glands rather than of pulmonary origin.

We are grateful to Gist H. Farr, MD (Ochsner Clinic Foundation, New Orleans, La), for contributing the case and to the Department of Scientific Laboratories for providing excellent technical support.


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(2.) Lewis JE, Olsen KD, Weiland LH. Acinic cell carcinoma: clinicopathologic review. Cancer. 1991;67:172-179.

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(11.) Moran CA, Suster S, Koss MN. Acinic cell carcinoma of the lung ("Fechner tumor"): a clinicopathologic, immunohistochemical, and ultrastructural study of five cases. Am J Surg Pathol. 1992;16:1039-1050.

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(15.) Schmidt-Kittler O, Ragg T, Daskalakis A, et al. From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc Natl Acad Sci USA. 2003;100:7737-7742.

Fabio Tavora, MD; Negar Rassaei, MD; Konstantin Shilo, MD; Robert D. Foss, DDS; Jeffrey R. Galvin, MD; William D. Travis, MD; Teri J. Franks, MD

Accepted for publication December 15, 2006.

From the Departments of Pulmonary and Mediastinal Pathology (Drs Tavora, Rassaei, Shilo, and Franks) and Oral and Maxillofacial Pathology (Dr Foss), Armed Forces Institute of Pathology, Washington, DC; the Department of Radiology, University of Maryland, Baltimore (Dr Galvin); and the Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (Dr Travis).

The authors have no relevant financial interest in the products or companies described in this article.

The opinions and assertions contained herein are the expressed views of the authors and are not to be construed as official or reflecting the views of the Departments of the Army or Defense. This is a US government work and, as such, is in the public domain in the United States of America.

Reprints: Konstantin Shilo, MD, Armed Forces Institute of Pathology, Pulmonary and Mediastinal Pathology, 6825 16th St NW, Washington, DC 20306 (e-mail: shilok@afip.osd.mil).
Distant Metastases From Salivary Gland Acinic Cell Adenocarcinoma

                       Total        Total          Lung
                       Cases,     Metastasis,   Metastasis,
      Study             No.           No.           No.

Spiro et al,
  (1) 1978               64            8             1
Perzin and LiVolsi,
  (5) 1979               49           12             4
Ellis and Corio,
  (3) 1983              294            7             1
Lewis et al,
  (2) 1991               63            8        ([dagger])

                       Bone         Other
                     Metastasis,    Sites,
      Study             No.           No.

Spiro et al,
  (1) 1978               1            6 *
Perzin and LiVolsi,
  (5) 1979               7            1 *
Ellis and Corio,
  (3) 1983               2            4 *
Lewis et al,
  (2) 1991           ([dagger])        *

* Multiple sites.

([dagger]) Lung more common than bone.
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