Salivary Duct Carcinoma: An Analysis of Four Cases with Review of Literature

Transcription

1 Salivary Duct Carcinoma: An Analysis of Four Cases with Review of Literature THOMAS A. GARLAND, M.D., DONALD J. INNES, J, M.D., AND ROBERT E. FECHNER, M.D. Salivary duct carcinoma (SDC) is a histologically distinctive neoplasm of the gland. The criteria for the diagnosis of SDC are circumscribed epithelial nests having a papillary, cribriform, and/or solid architecture coupled with central necrosis. The infiltrating cancer can be papillary, resembling the intraductal component or have a nonspecific, undifferentiated pattern. The authors are presenting four cases and compare them with 11 other acceptable cases from the literature. The neoplasm occurs beyond the age of 50 (median 63 years) and has a dismal prognosis with nearly two-thirds of the patients developing distant metastases. All surviving patients have been treated with combined ectomy and radiotherapy. (Key words: Salivary duct carcinoma; Parotid gland; Adenocarcinoma) Am J Clin Pathol 1984; 81: SALIVARY DUCT CARCINOMA is a histologically distinctive neoplasm of the salivary gland first described by Kleinsasser and co-workers" in Only eight additional cases have been reported. 3,5 The purpose of this article is to describe the clinical features of 4 new cases, and to refine the histologic criteria for the diagnosis. Material and Methods The Mclntire Tumor Registry of the University of Virginia Medical Center accessioned 76 carcinomas of the salivary gland between the years 1955 and Tissue slides from all of these neoplasms were reviewed, and three cases of salivary duct carcinoma (SDC) were identified. One additional case was seen in consultation. Detailed clinical information and follow-up were obtained on the three patients from the University of Virginia. Case 1 Clinical Data A 56-year-old white man presented in October 1979 with a mass anterior to the right tragus which had been present for four years. Hypoesthesia had been present over the right buccal area for one year, and right facial paralysis had been noted for one month. The patient underwent a radical ectomy with facial nerve cable graft. Postoperatively, he received 6,000 rads of radiation to the right area. Received June 10, 1983; received revised manuscript and accepted for publication July 29, Presented in part at the 77th meeting of the International Academy of Pathology, Atlanta, Georgia, March, Address reprint requests to Dr. Fechner: Box 214, Department of Pathology, Charlottesville, Virginia Department of Pathology, Division of Surgical Pathology, University of Virginia Medical Center, Charlottesville, Virginia Three years later he developed low back pain. A biopsy of an osteolytic lesion in the body of the tenth thoracic vertebra disclosed adenocarcinoma identical to the primary SDC. This was the only demonstrable metastasis. He received no therapy and remains well three months later. Case 2 An 83-year-old white man had a six-month history of "irritation" in his right external auditory canal. Because of intermittent bleeding, a biopsy was done in January 1981 that revealed carcinoma. On physical examination the canal was completely obstructed with a 2-cm mass. Facial nerve function was intact. A superficial ectomy with partial temporal bone core resection was performed. This was followed by 5,000 rads of radiation to the and neck. The patient is well 16 months later. Case 3 A 60-year-old white man presented in April 1973 with a one-year history of multiple right preauricular and neck masses. Physical examination revealed three masses: one in the area measuring 3.5 X 1 cm, one in the jugulodigastric area measuring 3X2 cm, and one in the posterior triangle measuring 3X2 cm. An incisional biopsy of the latter revealed adenocarcinoma. A total ectomy, mandibular resection, and right radical neck dissection were done. Postoperatively the patient received 5,000 rads of radiation to the neck. Forty months later a mass was detected in the thyroid. The tissue removed by partial thyroidectomy contained metastatic SDC. Five months later, roentgenogram of the chest showed a left perihilar mass with increased interstitial markings consistent with lymphangiectatic spread of carcinoma. He received Adriamycin, Cytoxan, and prednisone. There was no objective response, and he died 51 months after the initial diagnosis. There was no autopsy. Case 4 A 63-year-old man presented with a mass in his right neck. A frozen section diagnosis of adenocarcinoma was made and a ectomy and radical neck dissection was performed. No follow-up is available. Gross Findings Results The from Case 1 contained a single 1-cm firm, stellate, mottled yellow-white lesion. The tumor in Case 2 was widely distributed within the gland (Fig. 436

2 Vol. 81 -No. 4 SALIVARY DUCT CARCINOMA 1). It had yellow areas measuring up to 2 mm in diameter and cysts measuring up to 1.5 cm. The temporal bone portion of the resection was filled with granular yellow and gray tissue. The from Case 3 had multiple nodules of gray tissue measuring up to 1.5 cm in greatest diameter. The from Case 4 was extensively replaced by firm, gray tissue. Microscopic Findings All four cases had ductsfilledand distended with cells having a papillary, cribriform, or solid pattern that had central necrosis (Fig. 2). These are the distinctive features that distinguish SDC from all other salivary gland neoplasms. Most of the cells had powdery, eosinophilic cytoplasm, and there usually was a sharply defined cell margin. In addition, all tumors had cells with more coarsely granular, deeply eosinophilic cytoplasm resembling apocrine epithelium. The nuclei had evenly distributed chromatin and often had one or more nucleoli of widely varying size. Mucicarmine stains were negative on the three cases in which it was performed. In addition to the circumscribed nests, all tumors had an infiltrating component. In some foci it maintained a 437 papillary architecture similar to the circumscribed element (Fig. 3). In Cases 1, 2, and 4, the infiltrating tumor was poorly differentiated with ill-defined glands and in one instance (Case 2) there was extreme pleomorphism (Fig. 4). Infiltration always was accompanied by hyalinization of the stroma, and this reaction was especially prominent when the infiltrating component was poorly differentiated (Fig. 5). On hematoxylin and eosin sections, the stroma resembled elastosis, but elastic tissue was not demonstrable with VerhoefTs stain. Cases 2 and 4 had foci of vascular invasion and Cases 1 and 4 had marked perineural invasion (Fig. 3). Case 4 had foci of osseous metaplasia in the otherwise desmoplastic stroma. Cases 1 and 3 had ducts with only partial involvement by the neoplastic cells. Thickened epithelium and miniature papillary processes involved only a small sector of a normal duct (Fig. 6). This gave the impression of carcinoma in situ. In other foci, cells with large, dense nuclei were located within the epithelium without a papillary character. We consider this to be dysplasia and to be a minimal manifestation of the neoplastic spectrum. In three cases there was widespread involvement of the acini by cells cytologically identical to those in the larger FlG. 1. Parotid gland having multiple punctate foci of carcinoma. A portion of cyst wall is seen in the lower right part of the specimen. Ruler in millimeters (Case 2).

3 438 GARLAND, INNES, FECHNER AJ.C.P. April 1984 FIG. 2 (upper, left). Carcinoma has cribriform and papillary patterns. Central necrosis is present (Case 1). FIG. 3 (upper, right). Papillary pattern persists in the infiltrating component including focus of perineural invasion (Case 1). FIG. 4 (lower, left). Extreme pleomorphism is seen in some foci (Case 2). FIG. 5 (lower, right). Infiltrating component is associated with dense stromal hyalinization (Case 1).

4 Vol. 81 No. 4 SALIVARY DUCT CARCINOMA 439 ducts. In some instances the fortuitous angle of sectioning showed that the involved acini were in continuity with larger ducts. Two patients have had distant metastases. The metastases to the thyroid (Case 3) and bone (Case 1) retained features identical to their respective primary tumors (Fig. 7). Ultrastructural Findings Ultrastructural examination of Case 3 demonstrated intercellular and intracellular lumens lined by microvilli. In addition, there were irregular, cocoon-shaped collections of tubular or membrane material. These have been illustrated elsewhere, and their nature remains obscure. 8 Discussion We believe that the criteria for the diagnosis of SDC are (1) circumscribed epithelial nests with (2) central comedonecrosis. Whether the epithelium is confined within preexisting ducts or is a larger circumscribed nest of tumor no longer within a duct is immaterial. The appearances of the infiltrating component are variable, and therefore their patterns do not constitute a criterion for the diagnosis of SDC. The infiltrating cancer can have a papillary architecture resembling the intraductal tumor or a nonspecific, undifferentiated pattern. The variation in the appearance of the infiltrating carcinoma does not detract, however, from the diagnosis of SDC as long as the characteristic circumscribed, centrally necrotic epithelial component is present. The appropriateness of the term SDC is evident from the foci of dysplasia and sectorial changes that we interpret as carcinoma in situ in the large ducts. We believe this is evidence of a ductal origin. When SDC is defined as above, all of the previously reported cases, as well as our own, have been in the.*<-«-«i,a*,-''",.".'*": FIG. 6 (left). A sector of large duct is lined by neoplastic cells. Inset shows pleomorphic tumor cells with prominent nucleoli. Irregular lumens are present (Case 1). FIG. 7 (upper, right). Metastatic tumor to thyroid maintains papillary pattern with central necrosis identical to primary tumor (Case 3). FIG. 8 (lower, right). Papillary cancer from minor salivary gland lacks necrosis. A small amount of secretory material is in the lumen.

5 440 GARLAND, INNES, FECHNER A.J.C.P. April 1984 gland. Eleven of the 15 cases have been in males, but a larger number of cases is needed to be certain if this is significant. The prognostic importance of this histologic type is evidenced by the 65% of patients who have died of their tumor (Table 1). All current survivors have been treated with ectomy and radiation therapy. Chen and Hafez 3 have pointed out that two of the cases (4 and 5) reported by Kleinsasser and associates'' as SDC Table 1. Summary of Fifteen Patients with Salivary Duct Carcinoma Case No. Age (yr)/sex Primary Site Initial Symptoms FNI* Treatment Primary Tumor Recurrence Node Metastases Distant Metastases Outcome 1 56/F Rapid growing mass. Pain XRT* 17 mo. Skull Dead in Vh yrs 2 64/F Mass growing for 4 yr. Pain. Hearing loss Palliative partial resection Mandible. Auditory canal Dead /M 67/M 63/M 53/M 64/F 68/M 70/M 59/M 63/F 56/M Mass. Pain Mass Enlarging mass for 10 yr. Pain Dysphagia Hypoesthesia. Mass growing for 4 yr - ND* XRT, RND,* XRT, XRT, RND 5 mo later Partial resection XRT Excision ND XRT Radical ectomy XRT Submental. Supraclavicular. Locally persistent Probable brain Brain Skin. Liver. Bone Vertebral column Developed prostate CA with mets. Dead in 4 yr Alive at 6 yr Alive at 3 yr Dead in 2'h yr Dead in 3 yr Dead in 5 mo Dead in 3 yr Dead in 8 mo Alive at 2'h yr Alive at 3 yr 13 83/M "Irritated" auditory canal Superficial ectomy, partial temporal bone core resection, XRT Alive at 16 mo /M 63/M Masses growing for 1 yr Mass, RND, partial mandibular resection, XRT RND - Upper-jugular. Submandibular Jugular Thyroid. Dead in 4'A yr No follow-up Abbreviations: FNI = facial nerve involvement: XRT = radiation therapy: ND : = node dissection: RND = radical neck dissection. Cases 1-2. ref" Their cases 1 and 3. Cases 3-6. ref' Their cases I through 4. Cases ref 3 Their cases 1 through 5. Cases current series.

6 Vol. 81 No. 4 SALIVARY DUCT CARCINOMA 441 are better classified as the tubular carcinoma that was later delineated by Donath and associates. 4 Parenthetically, we believe that the lesion designated SDC by Thackray and Lucas (their Fig. 121) 12 is also better classified as tubular carcinoma. In addition, the tumor in Case 2 reported by KJeinsasser and associates'' has wellformed lumens with delicate papillary fronds. Although there is some debris within the lumens, comedonecrosis is absent. The lesion arose on the hard palate and the patient was well after four years. We have seen a morphologically identical case in the retromolar trigone (Fig. 8). The patient remains well nine years after resection. Papillary carcinoma without necrosis may well be a different clinico-pathologic entity characterized by origin in minor salivary glands and having an excellent response to excision. The differential diagnosis of SDC includes neoplasms of salivary glands that have lumens, are composed of cells with eosinophilic cytoplasm, or form papillary structures. Such tumors incude adenopapillary carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, malignant oncocytoma, and terminal duct carcinoma. The adenopapillary carcinomas reported by Blanck and co-workers can have small or large cysts, a well-developed fibrous stroma, and papillary projections. 2 In contrast to SDS, however, they lack comedonecrosis, uncommonly show perineural growth, do not invade blood vessels and do not have a cribriform pattern. Moreover, they secrete mucus. These tumors occur in a younger population (mean 38 years) than SDC. Acinic cell carcinoma may have a papillary cystic pattern and this may be associated with necrosis of the tumor. The cells of most acinic cell carcinomas, however, are more uniform and cytologically bland than the cells of SDC. The cytoplasm tends to be amphophilic or basophilic in contrast to the eosinophilic cytoplasm of the cells in SDC. Perhaps the most difficult lesion to distinguish from SDC is the poorly differentiated mucoepidermoid carcinoma. It may have necrosis and can form lumens. Wellformed papillary and cribriform patterns, however, rarely are seen. The presence of a squamous element, however poorly differentiated, distinguishes mucoepidermoid carcinoma from SDC. Poorly differentiated mucoepidermoid carcinomas focally produce mucin, which also differs from SDC. 79 Malignant oncocytomas are rare tumors of the that may be cystic and have a papillary pattern. These tumors have had perineural and intravascular invasion coupled with severe nuclear abnormalities and a high mitotic rate similar to SDC. 610 These cases, however, have not had comedonecrosis. The cytoplasm of the oncocytomas tends to be more abundant and more granular than most of the cells in SDC. Terminal duct carcinoma' should not be confused with SDC because of its composition of small tubules lined by small cells having oval to slightly spindled nuclei. These cells have a fine chromatin pattern, are unassociated with tumor necrosis, and do not form papillary configurations. Acknowledgment. The authors thank Miss Lynn Williams and Mrs. Carol A. Mills for expert secretarial support. References 1. Batsakis JG, Pinkston G, Luna MA: Terminal duct carcinoma of salivary tissues. Lab Invest 1983; 48:7A 2. Blanck C, Eneroth C-M, Jakobsson PA: Mucus-producing adenopapillary (non-epidermoid) carcinoma of the gland. Cancer 1971;28: Chen KTK, Hafez GR: Infiltrating salivary duct carcinoma. Arch Otolaryngol 1981; 107: Donath L, Seifert G, Schmitz R: Zur Diagnose und Ultrastruktur des tubularen Speichelgangcarcinoms: Epithelial-myoepitheliales Schaltstuckcarcinom. Virchows Arch Pathol Anat 1972; 356: Fayemi AO, Toker C: Salivary duct carcinoma. Arch Otolaryngol 1974; 99: Gray SR, Cornog J L, Seo IS: Oncocytic neoplasms of salivary gland. Cancer 1976;38: Healey WV, Perzin K.H, Smith L: Mucoepidermoid carcinoma of salivary gland origin. Cancer 1976; Innes DJ, Garland TA, Fechner RE: Structures in salivary gland intraductal adenocarcinoma. Ultrastruct Pathol 1982; 3: Jakobsson PA, Blanck C, Eneroth C-M: Mucoepidermoid carcinoma of the gland. Cancer 1968; 22: Johns ME, Batsakis JG, Short CD: Oncocytic and oncocytoid tumors of the salivary glands. Laryngoscope 1973: KJeinsasser O, Klein HJ, Hiibner G: Speichelgangcarcinoms: Ein den Milchgangcarcinomen der Brustdriise analoge Gruppe von Speicheldrusentumoren. Arch Klin Exp Ohre Nasen Kehlkopfheilkd. 1968; 192: Thackray AC, Lucas RB: Tumors of the major salivary glands, Atlas of tumor pathology, second series, fasc. 10. Armed Forces Institute of Pathology, Washington DC, 1974, p 102