Ann Otol Rhinal Laryngol99: 1990

PATHOLOGY CONSULTATION

HISTOPATHOLOGIC GRADING OF SALIVARY GLAND NEOPLASMS: I. MUCOEPIDERMOID CARCINOMAS JOHN

G.

BATSAKIS, MD

MARIO

A.

LUNA, MD

HOUSTON, TEXAS

Histopathologic grading of salivary gland neoplasms has been done with various degrees of success and hence various degrees of acceptance among pathologists and otolaryngologists-head and neck surgeons. Given their histopathologic diversity, three carcinomas - mucoepidermoid, adenoid cystic, and acinic cell - would seem to he suitable candidates for grading. In this, the first of a three-part series, the authors present a three-level grading scheme for mucoepidermoid carcinomas. It com hines histocytologic and growth features of the carcinomas that independently or together, in other grading proposals, have shown prognostic value.

Originally intended to subjectively convey the degree of differentiation of a neoplasm, histopathologic grading of malignancies is now employed to provide one of several variables considered useful in the assessment of biologic aggressiveness, response to therapy, and prognosis. The grade of a neoplasm is usually expressed in either numeric terms (1, 2, 3) or descriptively (well, moderately, or poorly differentiated). In some instances, adjectival descriptors alone serve the grading function, eg, myxoid liposarcoma, papillary thyroid carcinomas.

moid, and intermediate. The intermediate cell is well named, since it is likely the progenitor of the two other cells (Fig 1). It should also be appreciated that "epidermoid" is not synonomous with squamous, and its use is adjectival to signify squamouslike. Individual cell keratinization and certainly the development of keratin pearls are rarely seen in any mucoepidermoid carcinoma. Should they be prominent, mucoepidermoid carcinoma is unlikely. There is considerable variation in cell types, distribution of cells, and their growth pattern in the carcinomas. The histopathologic appearance of a mucoepidermoid carcinoma is the result of the interplay of the variations, with the cells arranging themselves in cystic or glandular structures, solid nests or cords, or combinations of these architectural displays. A chronic inflammatory cell reaction with or without fibrosis is often seen. If the neoplastic cells are well differentiated and cystic changes prominent, the chronic inflammation may suggest a sialadenitis with ductal metaplasia and ectasia. The sclerosing mucoepidermoid carcinoma epitomizes the pronounced hyalinization and fibrosis that can occur in mucoepidermoid carcinomas (Fig 2). None of the carcinomas are encapsulated, and while

Grading of salivary gland carcinomas has never had the acceptance or the degree of transferability to biologic activity credited to grading of other malignancies, eg, squamous cell carcinomas or sarcomas. Their relatively low incidence, numerous subtypes, and mandatory long follow-up periods may be the principal impediments, but lack of definition of the grading constituents is also responsible. It is also clear that grading subserves clinical stage and thoroughness of the primary surgical excision in nearly every instance. 1.2 For some salivary carcinomas, the classification itself implies the grade. The salivary duct carcinoma, for example, is a highgrade malignancy, as amply evinced by its high lethality. J The terminal duct adenocarcinoma of the palate, on the other hand, is biologically low-grade with a very low mortality. 4

0--------0 Epidermoid Cell

Reserve Cell of Salivary Duct Unit

Because they have a broader range of phenotypic expression and also biologic aggressiveness, mucoepidermoid, adenoid cystic, and acinic cell carcinomas would seem to be ideal candidates for an acceptable transfer of grade to biologic course. The following presents the status of and a proposal for the histopathologic grading of mucoepidermoid carcinomas.

Gf-----( Intermediate Cell

Squamous Cell

>----0 Mucous Cell

Clear Cell

Fig 1. Suggested histogenesis of mucoepidermoid carcinoma. In this scheme, intermediate cell is progenitor, through differentiation, for all other light microscopic phenotypes of mucoepidermoid carcinomas.

Mucoepidermoid carcinomas are basically composed of three cell types: mucin-secreting, epider-

From the University of Texas M. D. Anderson Cancer Center. Houston, Texas. REPRINTS - John G. Batsakis, MD, Dept of Pathology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030.

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adventitious scheme, Foote and Frazell," noting the arbitrary nature of this type of grading and also that some of their "benign lesions" had metastasized, concluded that all mucoepidermoid tumors were malignant, albeit in degrees: low, intermediate, and high grades.

Fig 2, Sclerosing mucoepidermoid carcinoma of parotid gland (H & E. original xl S). Only islands of histologically low-grade carcinomas are visihle in this extensively hyalosclerotic neoplasm,

nearly all convey an infiltrative quality, some may be circumscribed. That there is no uniformly accepted grading system for mucoepidermoid carcinomas despite nearly half a century of trying is testimony to 1) a lack of consensus as to what features should be used to formulate the grades and 2) an imperfect separation of grade, as an independent prognostic variable, from the size of the neoplasm and its clinical stage. It must also be understood that grading cannot substitute for appropriate histopathologic classification. In that light, the circumscribing of a classification to only those mucoepidermoid carcinomas that are easily recognized distorts the clinical implications of grading. The first attempt at grading of mucoepidermoid carcinomas led to a division into two groups: qualified benign (relatively favorable) and qualified malignant (highly unfavorable). 5 The authors of this

Three-level grading found general acceptance among pathologists, and differences in biologic behavior could be demonstrated even though clinical stage became the better prognosticator. Predictably, however, attacks on the three grades have been mounted. Some investigators place their emphasis on cellular characteristics, eg, level of differentiation, pleomorphism of cells, nuclear irregularities, number of mitoses.":" Others eschew such cytologic features and rely on growth patterns such as solid or cystic and "invasion. "9,10 Jakobsson et al'" determined grade solely from the presence or absence of "invasive growth," a quality neither defined nor well illustrated in their report. Indeed, unencapsulated carcinomas, especially those with an origin from ramifying ducts, possess an invasive appearance even though their cytologic features are rather banal. Evans," studying an ellipsis of mucoepidermoid carcinomas, also ignored cell types and differentiation to declare high-grade carcinomas to be those with a greater than 90 % solid architecture. All others are low-grade. Despite the observations from multivariate analyses that clinical stage at the time of diagnosis is the most important prognostic variable, the histologic features of salivary gland carcinomas are also independent factors that bear on patient outcome. 2 , 1I , 1 2 The trend to use only two grades (high and low) for mucoepidermoid carcinomas ignores the prognostic differences shown by authors who have used a three-tiered scheme. The 6%, 20%, and 78% recurrence rates for grades 1, 2, and 3, respectively, reported by Healey et all are very similar to those reported by others. Spiro et al, 13 in 1978, found that 5-year determinate cure rates were 92 % , 83 % , and

GRADES OF MUCOEPIDERMOID CARCINOMAS AND THEIR HISTOCYTOLOGIC CHARACTERISTICS

Grade 1 (Low)

Grade 2 (intermediate)

Grade 3 (High)

Macrocvsts and microcvsts; transitions with excretory ducts .

No macrocvsts; fewer microcvsts; solid nests of cell~ .

No macrocvsts; preponderantly solid, but may be nearly ail microcystic glandular

Differentiated mucin-producing cells and epidermoid cells, often in a I: I ratio; intermediate cell population minimal to moderate (focal)

Intermediate cell preponderance with or without epidermoid differentiation; mucin-producing cells may be sparse

Differentiated cells difficult to find, especially mucin-positive cells

Daughter cyst proliferation from larger cysts

Large duct population far less conspicuous

Cell constituents range from poorly differentiated to recognizable epidermoid and intermediate to ductal-type adenocarcinoma with epidermoid and intermediate cell participation

Minimal to absent pleomorphism and rare mitoses

Slight to moderate pleomorphism; few mitoses; nuclei and nucleoli more prominent

Considerable pleomorphism; prominent nucleoli; easily found mitoses

Broad-front. often circumscribed invasion

Invasive quality usually well defined and uncircumscribed

Unquestioned invasion: soft tissue, perineurial, and intravascular

Pools of extravasated mucin with stromal reaction (eg, fibrosis, chronic inflammatory cells)

Chronic inflammation at periphery: fibrosis separates nests of cells and groups of nests

Chronic inflammation less prominent; desmoplasia of stroma may outline invasive clusters

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Fig 3. Mucoepidermoid carcinomas. A) Low-grade (grade 1), of parotid gland, showing cystic architecture, mucous cells, and intermediate cells (H & E, original x60). B) Unicystic low-grade (grade 1), of parotid gland (H & E, original x60). Mucous cells of cyst lining have provoked foreign body reaction. C) Intermediategrade (grade 2), of parotid gland (H & E, original x220). Solid growth pattern with intermediate cells as preponderant population. Note beginning optical clarity of some of intermediate cells. D) Intermediate-grade (grade 2), of submandibular gland (H & E, original x220). There are more cells with clear cytoplasm and nuclear irregularity than in grade 2 carcinoma shown in C. E) Grade 3, of parotid gland, with invasive growth, nuclear and cytoplasmic pleomorphism, and partially ductal adenocarcinoma appearance (H & E, original x80).

-til

5-year survival rate of 42 % . A three-level grading system modeled after the one proposed by Healey et all forms a concinnity and is presented in the Table. It incorporates cytodifferentiation as well as growth patterns, emphasizes the intermediate cell population as an integral histogenetic and histologic component, and recog-

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Batsakis & Luna, Pathology Consultation

nizes poorly differentiated types of the carcinomas'

Histopathologic grading of salivary gland neoplasms: I. Mucoepidermoid carcinomas.

Histopathologic grading of salivary gland neoplasms has been done with various degrees of success and hence various degrees of acceptance among pathol...
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