Undifferentiated carcinomas of the major salivary glands Kathleen K. Hui, MD,’ Mario A. Luna, MD,” John G. Batsakis, MD,O Nelson G. Ordbfiez, MD,a and Randall Weber, MD,’ Houston, Texas UNIVERSITY

OF TEXAS

M.D. ANDERSON

CANCER

CENTER

Undifferentiated salivary carcinomas are defined as primary epithelial malignant neoplasms that are devoid of any phenotypic expression by light microscopy that would allow them to be otherwise classified. A clinicopathologic study of sixteen so-defined carcinomas of the major salivary glands is presented. The carcinomas are unquestionably high-grade malignant neoplasms. Ten of the sixteen patients were dead because of their disease within 4% years of histologic diagnosis. Cell size and ultrastructural features have little bearing on prognosis. The single most important clinicopathologic factor relating to patient outcome is size of the primary neoplasm. All patients with carcinomas larger than 4 cm died, and these carcinomas had nearly two times the incidence of perineural invasion, extrasalivary extension, and locoregional failure of control. (ORAL SURG ORAL MED ORAL PATHOL 1990;69:76-83)

T he World Health Organization (WHO) defines as

“undifferentiated” those malignant epithelial neoplasms of salivary glands that do not manifest enough light-optic phenotypic features to allow them to be placed into recognized categories of salivary carcinomas.’ As presented in the literature, undifferentiated carcinomas make up between 5% and 30% of all malignant salivary gland neoplasms.2-4We suggest there are several reasons for this rather wide spread in reported frequencies besides an institutional selection bias: (1) an ambiguous use of “undifferentiated” as a qualifying adjective, (2) inclusion of high-grade forms of otherwise classifiable carcinoma, and (3) failure to exclude metastasesto salivary glands. In this report, adhering to the WHO definition of “undifferentiated” and avoiding the three aforementioned potential pitfalls, we present a clinicopathologic analysis of undifferentiated carcinomas of major salivary glands.

aDepartment of Pathology, The University of Texas M. D. Anderson Cancer Center at Houston. hr\-- ,-A,-,--+ ,lf Il.--A ~nrl NW+ Sqrayv M.D. An&con Cancer Cenier at Houston. 7114112434

76

METHODS

AND MATERIALS

During the period between January 1961 and December 1984, 32 patients with a diagnosis of “undifferentiated malignancy” in their major salivary glands were admitted to the University of Texas M. D. Anderson Cancer Center for evaluation and/or treatment. After review of clinical records and histologic preparations, 16 patients were excluded from the study group for the following reasons: (1) two with nonepithelial malignant disease, (2) four with metastatic carcinomas to salivary glands (two with Merkel cell carcinomas from the scalp and two with oat carcinoma from the lung), (3) three with lymphoepithelial carcinomas, (4) three in whom tissue was insufficient for full evaluation, and (5) four whose neoplasms manifested sufficient light-optic differentiation to not warrant the undifferentiated adjective. The remaining 16 patients did not have a prior diagnosis or history of a carcinoma of the skin of the face, scalp, or lung. Their medical records were reviewed for demographic information, location and size of the primary neoplasm, evidence of local and distant metastases,mode of treatment, and follow-up periods. Histopathologic evaluation of the 16 patients’ neoplasms consisted of (1) study of an average of 9 (7 to

Volume Number

Undlxerentiated

69 1

salivary

carcinomas

Fig.

1. Small cell carcinoma of parotid gland. (Hematoxylin

and eosin stain. Original magnification,

Fig.

2. Large cell carcinoma, organoid pattern. (Hematoxylin and eosin stain. Original magnification.

77

X50.)

X50.) I 4) sections stained with hematoxylin and eosin from each primary neoplasm, (2) study of sections from each neoplasm stained with alcian blue, mucicarmine, Grime& and periodic acid-Schiff methods, and (3) study of immunoreactions in each neoplasm with antibodies against keratin, S- 100 protein antigen, HMB45, vimentin, desmin, and leukocyte common antigen (LCA).

Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections by means of the avidin biotin peroxidase complex (ABC) method.5T 6 Tissue specimens were cut 3 to 4 ,um thick, deparaffinized in xylene, and rehydrated in descending grades (100% to 70%) of ethanol. To enhance the immunostaining, sections were digested with 0.1% protease (type XIV, Sigma Chemical, St. Louis,

78

Hzri

rt

al.

ORAL

SURG

OKAl

MED

ORAL

January

Fig. 3. Trabecular x250.)

pattern of small cell carcinoma.

(Hematoxylin

Fig. 4. Small cell tumor showing cross section of cytoplasmic X 12,000.) (Original magnification,

Missouri) in phosphate buffer pH 7.6 for 30 minutes. Endogenous peroxidase activity was blocked with 3% nyurogen peroxide in absolute methanol for 10 minutes. Sections were incubated in a humid chamber with AE-%, a mixture of two mouse monoclonal antibodies (MAbs), AE1 and AEs, directed against hu-

and eosin stain. Original

process containing

PTtlOL

1990

magnification,

neurosecretory

granules.

man epidermal keratin (Boehringer-Mannheim, Indianapolis, Indiana, 1:400 dilution). The AEt keratin reacts with 40 kDa, 50 kDa, and 56.6 kDa classes of keratin proteins. The AEs antibody reacts with a 46 kDa, 52 kDa, 58 kDa, and 65 to 67 kDa classes of keratin.‘In addition, tissue sections were stained with

Volume Number

69 1

Undiflerentiated

salivary

carcinomas

Fig. 5. Group of cells having irregular nuclei and joined by numerouswell-developeddesmosomes. An elongatedmyoepithelium-likecell is seenat the periphery of the group. (Original magnification, x4,000.)

Fig. 6. Smalltumor cellshaving round nuclei andscanty cytoplasmwith sparseorganelles.(Original magnification, ~6,000.)

79

80

Hui et al.

ORAL

SURG

ORAL

MED

ORAL

PATHOL

January Table I. Pathologic characteristics relationship to survival

of undifferentiated

1990

carcinoma of major salivary glands and their Outcome-survival

No. of patients

Characteristic

NEDf

Sire of carcinoma Less than 4 cm 4 cm or larger Unknown

IO 4 2

5 4 1

3

Cell Size Small cell Large cell

12 4

Electron microscopy Neuroendocrine No distinguishing Ductal

differentiation

Perineural invasion Present Absent Lymphatic invasion Present Absent Blood vessel invasion Present Absent Extraglandular extension Present Absent Metastases to lymph node Present Absent Recurrences Present Absent Distant metastases Present Absent *DOD.

DOD*

died

of discax;

tNED,

no evidence

of disease;

$DOC,

DOC$

P

-Co.005

1

2 -

8 2

2 2

2 -