Polypoid spindle-cell carcinoma (pleomorphic carcinoma) Report review

Ayten Albert

of a case occurring of the literature

and

M.D.,* Zeyuel Karcioglu, M.D.,** A. Clairmont, Jr., M.D.,“** Atlanta, Na.

Sonaeren,

DEPARTMENTS SCHOOL

on tongue

OF OF

MEDICINE

PATHOLOGY AND

AND GRADY

OTOLBRYSGOLOGY, MEMORIAL

and EMORY

UNIVERSITY

HOSPITAL

A case of spindle-cell carcinoma (pleomorphic carcinoma), a rare polypoid tumor of the tongue, is reported. The characteristic clinical, gross, and microscopic features of this peculiar lesion and its common sites of locat,ion are presented. Origin and pathogenesis of the sarcoma-like elements of the lesion are discussed and the literature on the subject is reviewed. Sites of apparent transition between the spindlecell elements of the tumor and the overlying epithelium were observed in light microscopic sections, and the electron micrographs of the spindle-cell portion of the lesion demonstrated the presence of tonofilaments and desmosomes in many tumor ~11s. Thew findings support the concept that this group of lesions are pleomorphic variants of squamous-cell carcinoma with prwlominantly spindlw:ell pattern. Current evidence in thp literature also suggests that mrt~aplastia transformation of the tumor cells into mesmchymal c+ments may take place in some of these lesions, and that “metaplastic: carcinoma” nray probably be a more proper designation for them.

P

olypoid spindle-cell carcinoma is a rare malignant tumor that has been reported in the upper alimentary and respiratory tracts. This tumor characteristically is made up of carcinomatous and “sarcomatous” (sarcoma-like) elements: the former is seen usually at or near the stalk in the form of either in situ or invasive squamous-cell carcinoma and the latter forms the main bulk of the polypoid mass, often sharply demarcated from the epithelial elements. *Associate Professor of Pathology. **Assistant, Professor of Pathology. ***Special Fellow to John Conley, M.D., and St. Vincent’s Hospitals, New York, N. University School of Medicine.

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Head and P. Formerly

Neck Service, Resident in

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The origin of the spindle cells of the lesion and their nature have not been clearly established and resulted in considerable controversy on the subject,. Although several reports in the literature support the non-neoplastic basis for the spindle-cell proliferation concept originally suggested by I~ane,Y2 others present, evidence, ljascd on light and electron microscopic observations and tissue cultures, to support a true neoplastic epithclial component within the polypoid masses.“, 24,33-33 \Vc report a case of polypoid spindle-cell carcinoma (plcomorphic carcinoma) of the tongue and review the controversy that exists in the literature conccming the histogenesis of this lesion. We feel that the light and electron microscopic findings in this case add further support to the present consensus that the source of the spindle-cell component of this tumor is cpithelial, and the variOLIS tumor ccl1 forms encountered in the stroma all stem from the squamous epithelium. CASE REPORT Approximately 2 months prior to admission to the hospital this 67.year-old white man noted soreness and a rather rapidly enlarging mass on the right side of his tongue. He :rlso noted dysplragia and was limiting his intake to soft foods. The examination confirmed the 3 11y 4 cm. firm, mobile, polypoid mass at the junction of the anterior and middle thirds of the tongue, on the right lateral border. There mere no palpable cervical lymph nodes; nor was there clinical evidence of lung or liver metastases. On Jan. 31, 1974, the patient underwent a hemiglossrctomy after :I preliminary wedge biopsy which showed a spindle-cell carcinoma. Uuring a routine follow-up examination in July, 1974, a 1 by 1 cm., firm, but mobile lymph node was noted in the right subdigastric area, as w-cl1 as another 1 by 1 cm. nonfixed lymph node in the right submaxillary region. The patient rcccivcd 5,000 rads of cobalt-60 radiation therapy in 5 weeks to the tongue, floor of the mouth, and upper cervical nodes through a single lateral port of 8 by 11 cm. The lower lateral right. neck was treated through a separate port, 5,000 rads total, in 4 weeks’ time. A right radical neck dissection was subsequently performed on Oct. 22, 1974, and all eighteen lymph nodrs in the surgical specimen were found to be free of metastatic tumor. ‘l’hreo months after the operation, the patient returned to the outpatient clinic with a 0.5 cm. firm nodule in the surgical scar on the neck. There was no lymphadenopathy or any clinical evidence of recurrent tumor in the oral cavity. The nodule was not biopsied. Chest x-ray showed two sni:~lI, questionable, ill-defined densities in the right lung. It was decided to give an additional 3,000 rads in 15 fractions to the right side of the neck, but he failed to keep his appointments. The patient was found dead at his home in March, 1975, approximately 13 months after t~cnuglossertomy. No autopsy was performed.

PATHOLOGY

The surgical specimen consisted of a hemisected tongue. On the lateral aspect of the tongue a polypoid mass measuring 3 by 4 by 4 cm. was present (Fig. 111). The lesion was attached to the mucosal surface of the tongue with a short, broad pedicle. The tumor was rubbery, grossly devoid of epithelial c.overing, and tannish white on the cut surfaces. Rlicroscopically, the entire surface of the polypoid mass was ulcerated (Fig. 1B). Cnderlying the ulceration was granulation tissue with acute and chronic inflammation. The surface cpithelium was identified only on the stalk. The bulk of the polypoid mass was composed of spindle-shaped cells, separated by

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Fig. ld. Hemiglossectomy of the tongue.

E‘ig. m. tion, x6.

ad

Oral Surg. October, 1976

Clairmont

specimen demonstrating

Low-pa ~wer view of the polypoid

lesion.

the polypoid

(Hematoxylin

mass on the lateral

aspect

and eosi ‘n Estain. Magni fica-

delicate connective tissue strands. Some of the cells were enlarged, round or polygonal, with oval nuclei and abundant cytoplasm. 3Iultinucleatcd bizarre giant cells were also seen scattered among other elements. Nuclei of the spindle-shaped cells were variable in size and shape, rather vesicular, and with prominent nucleoli. Mitotic figures, including many abnormal forms, numbering up to four per

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Fig. 2. 8, Spindle-cell elements of the tumor with scattered inflammatory cells and areas of necrosis. (Hemztoxylin and eosin stain. Magnification, x310.) B, High-power view of the spin& cells (Hematoxylin and eosin stain. Magnification, x490.)

high-power field, were also observed. MaTip of the spindle-shaped cells had abundant, finely granular, cosinophilic cytoplasms. Cross striations were not identified. Scattered throughout the tumor were focal areas of necrosis and acute inflammation (Fig. 2). The mucosa of the base of the pedicle of the lesion showed areas of dysplasia and, in small foci, superficially invasive squamous-cell carcinoma. Keratinization with pearl formation and intercellular bridges were seen in these foci, unquestionably proving the squamous nature of the infiltrating cells. At the periphery of these infiltrating squamous islands, transitional zones from squamous cells to spindle cells were clearly seen (Fig. 3), Electron microscopic examination was also performed on formalin-fixed and paraffin-embedded material. Although the preservation and fine structural detail were not optimal, certain features of the spindle cells provided sufficient evidence

Oral Surg. October,

1976

Fig. 3. Transitional zone between malignant squamous cells and spindle cells of tumor and dysplasia in the surface cpithclium. (Hemxtoxplin and eosin stain. Magnification, x190.)

for their epithelial nature. Two basic cell types were identified. The first type was an elongated cell with abundant cytoplasm filled with rough endoplasmic reticulum and disrupted mitochondria. The nuclei were large, occasionally multiple, and showed chromatin clumpin g and peripheral condensation. Poorly defined desmosomes were occasionally obserrcd. Tonofilaments in bundles were seen interspersed between the organelles of these tumor cells (Fig. 4). Although attachment of the tonofilaments to the desmosomes could not be seen, in some cells they were located very close to one another. When compared to normal squamous cells, both desmosomes and tonofilaments were noted to be markedly diminished in number. The other cell type was seen less frequently. It was a smaller cell with an irregular outline. The endoplasmic reticulum showed varying sizes of cisternae. Irregular clumps of collagen fibers were present in the vicinity of these cells. They were similar to those describetl by Lichtiger, Mackay, and TessmerzC and Goellner, I)evine, and W’eilandzz and were thought to be reactive fibroblasts. It. was our feeling that the ultrastructural features of the lesion were compatible with those of a poorly differentiated spindle-cell squamous carcinoma as described by Greene, Brown, and I>ivertic,l” Lichtiger and associates,‘4 and Shields, Eilert, and Battifora.“’ REVIEW

OF THE LITERATURE

Polypoid spindle-cell carcinoma (plemorphic carcinoma) is a rare form of squamous-cell carcinoma. which received wide publicity in the English language literature after the description by Stout and Lattes3” in 1957. These authors described two cases of pedunculated mass of sarcoma-like tissue, occurring in the esophagus, associated with an in situ or superficially invasive squamous-cell carcinoma, usually found in the vicinity of the pedicle. Stout and Lattes believed that these lesions had the behavior of a rather benign tumor. Since the

Polypoid

Volume 42 Number 4

Pig. 4. Electron desmosomes (arrows)

microscopic appearance and tonofilaments (T).

spindle-cell

car&mm

of the elongated tumor cell with poorly (Magnification, ~10,000; inset, ~6,400.)

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apparent “Sarcomatous” component never metastasized, they referred to these tumors as “pscudosarcomas,” thus separating them from another group of polypoid tumors of the esophagus, the so-called “carcinosarcomas,” in which the sarcomatous elements tended to metastasize. The first report in the literature referring to the lesions under discussion appears to be that of Kettlezl published in 1919. This author presented a paper to the Royal Society of Medicine entitled “On the polymorphism of the malignant epithelial cell” and reported a case of squamous-cell carcinoma of the epiglottis in combination with a spindle-cell sarcoma occurring in a GO-year-old man. He described loosening and fraying out of the carcinoma cells and a direct transformation of them into sarcomatous tissue. Baker and Lambert,” in 1934, published a case of a polypoid swelling on the right vocal cord of a 59-year-old man. This case was interpreted as a sarcoma by two of the reviewing pathologists but the third pathologist regarded the lesion as a “polymorphic prickle-cell carcinoma with spindle and giant-cell formation.” The first classic paper on the subject of tumors under discussion, however, and the tumors that feature both epithelial and connective tissue components in general was that by Saphir and Vass,“2 published in 1938. These authors reviewed the literature on “carcinosarcomas,” analyzing 153 cases, including fourteen of the esophagus, six of the larynx, and seven of the lungs, and concluded that only four or five of these cases could be designated as true “carcinosarcoma” with metastasizing ability of the sarcomatous elements. The cases rejected by Saphir and Vass, on the other hand, were quite similar to the lesions under discussion. They were often polypoid, invariably with squamous-cell carcinoma in the surface epithelium, and with a spindle-cell “stroma” showing pleomorphic bizarre cells, including giant forms. The authors proposed that the sarcomatous appearance was due to either morphologic variations of squamouscell carcinomas, particularly of the poorly differentiated variety, or chronic irritation and inflammatory reaction of stroma. According to their interpretation of the case reports, the metastatic rate of this patricular group of “carcinosarcomas” was extraordinarily low, Several other so-called “carcinosarcomas” were reported in larynx, oral cavity, esophagus, and bronchi following the review by Saphir and Vass in 1938 and before the description of “pseudosarcoma” b)- Stout and Lattes in 1957.“. “, 3’S” Frank and Lev” and Pearlman :j” felt that these lesions were examples of squamous-cell carcinoma and demonstrated spindle-shaped “transitional” carcinoma cells in their cases. Bergmann, Ackerman, and Kemler’ and Stout, Humphreys, and Rottenberg,“” however, interpreted their own cases and some cases that they selected from the literature as “carcinosarcomas,” reporting combined metastases with both carcinomatous and sarcomatous components and, in some, independent metastases by sarcomatous component, which they felt unquestionably qualified these tumors as “carcinosarcomas.” Lane,22 also in 1957, reported ten cases of polppoid spindle-cell tumor occurring in the mouth, fauces, and larynx and reviewed the literature on the subject rather extensively. He proposed that these lesions were non-neoplastic polypoid connective tissue masses with histologic features suggestive of sarcoma, adjacent

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to a squamous-cell carcinoma, and introduced a new name for the entity: “pseudosarcoma associated with carcinoma.” As was also noted by Saphir and Vassa2 and Stout and Lattes, 39in all of Lane’s cases and the cases he selected from the literature the associated squamous-cell carcinoma was either inconspicuous or in situ. In differentiating these tumors from carcinosarcomas, Lane” mentioned that there was merely side-by-side positioning of sarcomatous and carcinomatous elements in pseudosarcomas, whereas in carcinosarcomas there was an extensive an intimate intermingling. The possibility that the pseudosarcomatous component of these tumors may represent a bizarre morphologic variant of the associated carcinoma was also mentioned by Lane ** but he rejected this idea for several reasons : (1) the morphologic appearance which suggests a non-neoplastic nature, (2) the well-differentiated appearance of the associated squamous-cell carcinoma, (3) distinct separation of the normal mucosa and carcinoma from the so-called “pseudosarcomatous” tissue, and (4) reticulin stains showing cells that are enveloped by fibers. Clinical “cure” of some of these cases by what was considered to be inadequate surgery was also mentioned by Lane as clinical evidence against these lesions being anaplastic squamous carcinomas. He also noted that the sarcomatoid component of these lesions failed to metastasize and questioned its neoplastic nature. Because of the reasons enumerated above, he proposed that the sarcoma-like component of these tumors is an exaggerated reparative connective tissue response to a stimulation by the overlying in situ or superficially invasive carcinoma. Following the description by Stout and Lattes39 of the two esophageal cases in 1957 and the review article by Lane22 which appeared the same year, several additional cases of a polypoid spindle-cell tumor of similar nature occurring in larynx, pharynx, esophagus, oral cavity, and lungs were reported. Controversy as to the nature of the spindle-cell elements of these tumors, however, continued to exist.1, 2, 10,12,14,17,18,28,29,33,35,40 Baker,” Qrigg, Rachmaninoff, and Robb,‘* and Fraser and Kinley’o were in agreement with the view that the polypoid spindle-cell growth, in these lesions, is of connective-tissue origin and that. they have a favorable prognosis. In their reports, several histologic features in favor of a benign reactive lesion were mentioned repeatedly. Sorris and Peale2” described two cases of polypoid spindle-cell tumor in the larynx and admitted that these might be regarded as carcinosarcoma, but preferred to classify them as “pseudosarcoma of Lane.” Appelman and Oberman,l Greene and Bernier,lz Mittelman and associates,‘R Hay-Roe, Hill, and Civin,17 Sherwin, Strong, and Vaughn3” Talbert, Cantrell, and Blalock,40 Scarpa,” and Himalstein and Humphrey,ls on the other hand, were more inclined to believe that the lesions basically are epithelial tumors, and that the bizarre spindle-shaped areas are merely poorly differentiated variants of squamous carcinoma cells. Three of the eleven laryngeal cases reported by Appelman and Obermanl also had osseous and cartilagenous foci. All of these patients, however, had in common a prior history of irradiation. It was thought by these authors that ne\v bone and cartilage formation in these cases was probably a non-neoplastic, bizarre reactive

Oral Surg. October, 1976

change in the stroma. Another interesting feature described by Appelman and Oberman was sessile and ulceroinfiltrativc gross appearance in seven of their cases, as opposed to the usual polypoid configuration reported more frequently. These patients did very poorly. Reports by Hay-Roe,” Sherwin,“” Talbert,4” and their associates and Scarpa”” seem to provide strong evidence that the spindle-cell component of these lesions is formed by proliferation of spindle cells of squamous origin, together with granulation tissue, as a response to the infiltrating tumor. Tissue cultures of an esophageal polypoid spindle-cell carcinoma were performed by Hay-Roe and colleagues,li and they were able to propagate both polygonal and spindle cells depending on the site of the tissue. The ability of a tumor to have autonomous growth indicated malignam>- to many investigators. They believed that the spindling was probably derived from the epithelial elements of the tumor. Sherwin and associateP demonstrated loss of cohesion of the basal cell layer of the squamous epithelium overlying the polypoid mass, in two cases occurring in the tongue and one in the larynx. They emphasized this feature as being a major factor in the pathogenesis of the lesion and also mentioned that the spindle-cell growth pattern may also be found in these tumors within the squamous epithelium itself, in areas of carcinoma in situ, adjacent to polyp. Talbert and associateP reported four cases of so-called “carcinosarcoma” occurring in the esophagus and emphasized the presence of transitional zones between the epithelial and “sarcomatous” components of these lesions. They interpreted this feature as possible evidence for the common origin of the two cell types. Scarpa described a case of polvpoid undifferentiated squamous carcinoma occurring in the esophagus, with minimal spindle-cell metaplasia. This author felt that this finding suggests the early formation of a component that eventually might have appeared “sarcomatous” and lends further strength to the view that the “sarcomatous” cells of many so-called “carcinosarcomas” are metaplastic derivatives of epithelial cells. Himalstein and Humphrey,l” in 1968, reported two cases occurring in the larynx and introduced a new name for the entity-“pleomorphic carcinoma.” They believed that all of the various tumor cell forms encountered in the stroma of these lesions stem from the squamous epithelium. These authors described “pleomorphic carcinoma” as a “strictly epithelial tumor with pleomorphic forms of the cells replacing in part the stroma.” They believed, however, that the pleomorphic carcinoma differs from the spindle-cell (Grade IV) epidermoid carcinoma in that t,he sarcoma-like stroma of these lesions is very pleomorphic and shows variable patterns. They also stressed the point that the identifiable squamous-cell component in these lesions is focal, usually in situ, or focally invasive well-differentiated carcinoma. One of their cases had a. metastatic lesion in a cervical node with a well-differentiated squamous-cell pattern. Because of the lack of spindle-cell component at the metastatic site, they excluded the possibility in their case of “carcinosarcoma.‘! Although by 1968 the general consensus as to the nature of the spindle-cell

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elements of these lesions was in favor of the squamous epithelium, additional case reports continued to confuse the issue. Staley, Ujiki, and Yokoo,37 in 1971, reported a case which occurred in the larynx and metastasized to the neck nodes and lungs. Independent squamous-cell and spindle-cell metastases with areas of osteoid and cartilage were found in the neck nodes, At autopsy there were strictly spindle-cell tumor metastases in the lungs, This patient had no history of irradiation. These authors interpreted their case as an example of “pseudosarcoma” in which carcinomatous and so-called “sarcomatous” components demonstrated independent metastatic capability. In 1969 Davies6 reported a case of fibrosarcoma and two cases (one polypoid, one non-polypoid) of “pseudosarcoma” occurring in the larynx. He supported the view that the so-called “pseudosarcoma” is probably a variant of squamous-cell sarcoma, and suggested that many cases interpreted in the past as fibrosarcoma occurring in elderly persons are probably of epithelial origin. Gelfman and Williams,ll also in 1969, reported a case of a “spindle-cell carcinoma” of the tongue and emphasized the fact that the true epithelial nature of these tumors may be masked by an abundant sarcomatous-appearing stroma. Enrile and associates,s in 1973, reported a case occurring in the esophagus and interpreted it as “pseudosarcoma.” These authors emphasized the benign clinical behavior of the “sarcomatous” component and the sharp demarcation of the two components of the lesion distinctly separating it from carcinosarcoma. Snyder, Myers, and Steinberg,36 in 1974, reported a case of “polypoid squamous carcinoma” of the floor of the mouth and presented histologic evidence in support of the view that the sarcomatous areas actually consist of altered spindled neoplastic squamous cells. Randall, Alonso, and Ogura,31 in 1975, presented nine laryngeal cases of “spindle-cell carcinoma,” two with neck node and lung metastases with combined squamous and spindle-cell pattern and a third showing cervical node metastases with spindle-cell pattern. These authors also felt that their case demonstrated the metastasizing capability of the “sareomatous” element. Divergence of opinions as to the pathogenesis and clinical behavior of the polypoid spindle-cell tumors is best represented in two recent reports by Miller*” and HyamP in 1975. These papers and following panel discussion were presented at the Centennial Conference on laryngeal cancer in Toronto in May of 1974. Whereas Hyams *Obelieved and presented evidence to support the contention that the lesion pathogenetically is a pleomorphic or spindle-cell squamous-cell carcinoma, Mille? forcefully stated that the “pseudosarcoma” exists as a distinct entity separate from “spindle-cell carcinoma” and so-called “carcinosarcoma,” and it is not a true malignancy. It was hoped earlier that the ultrastructural studies may shed light on the controversy concerning the nature of the spindle-cell component of these lesions. At the time of this reporting, there are five papers in the literature on the ultrastructure of these tumors. Findings do not seem to clarify the issue, however, and the controversy still exists. The first two of these reports appeared in 1970. Minkler, Meligro, and NorrisZ7 reported a case which they called “carcinosarcoma” occurring in the larynx. This

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patient, after preliminary biopsy which showed squamous-cell carcinoma, received irradiation followed by laryngectomy and radical neck dissection. The tumor had the usual squamous and spindle-cell (“sarcomatous”) components, and one neck node showed metastatic squamous-cell carcinoma. The patient died 15 months after the initial diagnosis with massive recurrence and metastatic disease in the larynx, lungs, liver, and adrenal glands, all of which showed spindle-cell pattern. Ultrastructurally, at metastatic sites, this tumor demonstrated collagen external to the plasma membrane of the malignant cells. Also seen was basal laminar material surrounding an occasional single cell or group of cells. Only one structure resembling junctional complex or desmosome was observed between malignant cells, but no tonofilaments or keratohyaline granules were demonstrated. Although these authors believed that their case is a true “carcinosarcoma,” with light microscopic appearance of “fibrosarcoma” at recurrence and metastatic sites, their electron microscopic findings are not convincing and are difficult to analyze. The report published in 19’iO by Lichtiger and associates’” also provides light and electron microscopic evidence for epithelial derivation of the spindle cells of these polypoid tumors. Apparent continuity was demonstrated by these authors in all of their cases between t,umor and the overlying epithelium on light microscopy. In addition, their ultrastructural studies demonstrated the presence of aggregates of keratohyaline and slender bundles of tonofilaments, as well as occasional premelanosomes. Desmosomes were also seen, but were few and poorly preserved. These authors could demonstrate no ultrastructural evidence of malignant connective tissue components. They felt that their findings justify the designation of these tumors as “spindle-cell variants of squamous-cell carcinoma, ” and that the response of the connective tissue to the infiltrating tumor is reactive and not neoplastic. Our light and electron microscopic findings are comparable to those of Lichtiger and associates.‘* In 1972 Shields and co-workerP reported a case of “pseudosarcoma of the esophagus” with electron microscopic studies. These authors demonstrated tonofibrils and particularly desmosome-associated tonofibrils in the sarcoma-like cells of the tumor. These findings, they believed, definitely establish the squamous epithelial origin of spindle cells, They also suggested that the origin of these tumors may be the basal cells of the surface epithelium, as they arc often seen “dropping off” into the stroma. Scarcity of the tonofilaments, frequent accompaniment of desmoplastic reaction, and relatively benign behavior of these lesions, according to these authors, may also be related to their origin in basal cells. A report by Goellner and associates15 published in 1973 includes 25 laryngeal cases. In one of their cases the authors identified fibroblasts, macrophages, and a third cell population with ultrastructural features of both fibroblasts and macrophages. Based on their electron microscopy and enzyme histochemistry finding, they concluded that the pseudosarcomatous stroma is a reactive proliferation of histiocytes and fibroblasts, apparently in response to the squamous-cell carcinoma, and retained the name “pseudosarcoma.” The most recent report by Leifer and associates’” in 1974 describes two tumors of the tongue, both initially showing squamous-cell carcinoma in biopsy. One of

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these patients had a previous history of irradiation. Both lesions showed the usual mixture of squamous and spindle-cell components at recurrence, and both had neck node metastases showing only spindle-cell tumor. Electron microscopic findings in metastatie sites showed abundant intracellular collagen and tumor cells resembling fibroblasts. These were comparable to the cells seen in fibroblastic portions of osteogenic sarcoma. Areas of calcified osteoid were also seen. No desmosomes, tonofilaments, or junctional complexes were identified. These authors believed that the sarcoma-like tumor cells were formed by transformation of the epithelial cells at recurrent sites and possessed their own malignant potential. They also believed that their cases were examples of “spindle-cell squamous carcinomas” with light microscopic evidence of demonstrable transition. DISCUSSION

“Spindle-cell epidermoid carcinoma,” as pointed out by Martin and Stewart,“5 is an old concept. To quote Martin and Stewart,25 “ The concept of spindle-cell metaplasia in various types of epidermoid carcinoma is far from new. Such changes in structure were clearly recognized by Krompecker as early as 1900.” Krompecker was very impressed by these metaplastic changes in the epithelium and believed that in certain epitheliomas spindle-shaped basal cells underwent a gradual metamorphosis into connective tissue cells and into true fibrous tissue. Although this view, which was proposed by Krompecker in 1905, is not generally held today, some of the current ultrastructural evidence seems to be supportive of it. Dal-Pazzo, cited by Saphir and Vass3’ used the term “pseudosareomatous carcinoma” or “pseudocarcinosarcoma” to describe carcinoma with sarcoma-like appearance in the Italian literature in 1931. The main reason for the somewhat poor acceptance of this concept appears to be the difficulty in demonstration of transitional forms of tumor cells between the well-differentiated squamous and spindle-cell elements. It has been stated by many authors that the extreme spindle-cell change in these epidermoid tumors is probably due to the nature of the invaded tissue. Scarring, irradiation, infection, pressure, and other mechanical factors have also been suggested as being influentialZ5, 41,42 Lichtiger and associatesZ4 proposed that the breakdown of tonofilaments and their detachments from desmosomes, as seen ultrastructurally, might cause a decrease in the cytoplasm’s resistance to deformation, and the cells may become more susceptible to molding. This explanation of spindle-cell transformation of squamous-cell carcinoma cells seems reasonable, but not totally convincing, as paucity and abnormal configuration of tonofilaments and desmosomes have also been described in poorly differentiated squamous-cell carcinoma without spindlecell transformation. The ability of pleomorphic carcinoma cells of different types to simulate various types of sarcoma is also well known.‘, 5, 25,42,43In his excellent study, Bro&$ reviewed 110 cases of “sarcoma-like carcinoma” from skin, lip, ora] cavity, nasopharynx, lungs, gastrointestinal tract, and thyroid and concluded that diffuse sarcoma-like growth by carcinoma cells is probably not due to the factors in the

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invaded tissue but is an inherent characteristic of the cells of the particular carcinoma. Metaplastic changes in the direction of squamous, pseudosarcomatous spindle, and giant-cell patterns are also common in so-called “metaplastic carcinoma of the breast.” Further mesenchymal differentiation, including chondroid and osteoid, is frequent in malignant and benign tumors of the mammary and salivary glands. It is interesting to note that osteoid and/or chondroid areas were described on light and electron microscopy of some of the pleomorphic spindle-cell carcinomas under discussion.l, 23.37 At present it is believed that the mesenchymal elements in the mammary and salivary gland tumors are produced, at least in part, by the pluripotential myoepithelial cells of these organs through metaplastic transformationl” Although direct evidence of metaplasia of this type is lacking in the case of pleomorphic spindle-cell carcinoma of the upper respiratory and alimentary tracts, current light and electron microscopic evidence seems to suggest the possibility of such a biologic transformation. We feel that our case, as well as the reports by Sherwin,35 Grigg,14 Lichtiger,24 and their colleagues clearly demonstrate that a zone of transition between the squamous-cell and the spindle-cell components of these tumors can be seen on light microscopy if multiple sections are examined, and that the demarcation between the normal and the neoplastic epithelium from the spindle-celled (sarcomalike) tissue is not always as sharp as mentioned earlier by L,ane.*” Constant findings in almost all the reported cases of poorly preserved surface epithelium which could usually be seen only at the base of the lesion and around the stalk, together with inflammation and granulation tissue, appear to be the major factors in the difficulty of demonstrating a transitional pattern on light microscopic examination of these lesions. The reason for the rather exuberant stromal reaction seen in most of the cases is unknown. Lanez2 suggested that the loose connective tissue of these locations might be particularly susceptible to swelling and inflammatory change from a variety of conditions. The polypoid structure of the majority of these tumors seems also to be partly the result of mucosal ulceration and granulation tissue overgrowth. Currently, light and electron microscopic evidence seems to indicate that these tumors are pleomorphic variants of squamous-cell carcinoma with some ultrastructural evidence suggestive of differentiation of epithelial cells to fibroblastlike mesenchymal cells. Electron microscopic demonstrations at primary and metastatic sites of malignant squamous epithelial cells,24, 34 fibroblast-like cells with malignant characteristics resembling those seen in fibroblastic portions of osteogenic sarcoma,23 and “transitional forms of tumor cells” possessing some of the characteristics of both the epithelial and mesenchymal cells” are in favor of such a transformation. In addition, the presence of fibroblasts and histiocytes with reactive features as reported by Goellner and associateP and Lichtiger and associatesz4 seems also to indicate that there is a reactive component within the spindle-cell portion of these tumors. The diversity of the electron microscopic findings on reported cases may be related to the sampling of different portions of these tumors in which the cell composition is variable. On the other hand, the pres-

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ence of many cell types may simply be the reflection of metaplastic transformation. It has been the general feeling since the descriptions by Stout and Lattes?” and Lane2* that the polypoid spindle-cell carcinomas of the upper respiratory and alimentary tracts have a favorable prognosis. There are, however, by now numerous cases reported13 lR, I9322,23,27.w w 36 in which lymph node and lung metastases and recurrence had occurred and the prognosis was very poor. It has been concluded by Appelman and Oberman’ that the prognosis of these lesions is more closely correlated with gross configuration than with histologic appearance. Filotico and Trabucco, cited by Davies,” also suggested that the so-called “pseudosarcoma” can be divided into two types. The first type is characterized by polypoid configuration and a very good prognosis and a second type has an infiltrative appearance and showing the usual clinical behavior of invasive squamous-cell carcinoma. Randall and associates 31 however, stated that it is the size and the location of the lesion and not the gross configuration that determines the prognosis. In conclusion, the spindle-cell neoplasms of the upper respiratory and alimentary tracts are unique lesions which pose difficult interpretative problems for the pathologist and therapeutic problems for the clinician. Recent studies seem to prove, however, that the majority of these neoplasms are “pleomorphic squamous carcinomas with predominantly spindle-cell pattern.” In the differential diagnosis of these tumors, however, valid carcinosarcomas, true sarcomas, and true collision tumors should be considered, but great care must be taken in their diagnosis. The important point is the need for the awareness of the surgeon and the pathologist of the existence of this group of lesions. Polypoid lesions in upper respiratory and alimentary tract,s should alert the surgeon to the possibility of pleomorphic carcinoma. Therefore, if a lesion appears sarcoma-like microscopically, the pathologist should search, at multiple sections if necessary, for an identifiable squamous-cell carcinoma component in the base of the tumor, for continuity of the tumor with the overlying atypical epithelium, and for evidence of intercellular bridges between attached cells. Although most of these polypoid spindle-cell tumors seem to have a better prognosis than ordinary squamous carcinomas, true carcinosarcomas, and sarcomas occurring in the same locations, they can and do metastasize and should be treated as squamous carcinomas with metastasizing ability. It appears that the favorable outcome of the lesions which are polypoid is most likely due to their superficial location and the nature of the exophytic growth with early onset of symptoms, which bring the patient to the medical attention while the lesions are still surgically curable. The lesions which are sessile or infiltrative, however, have a poorer prognosis and should be considered as serious as any other invasive carcinoma. The authors are indebted to Drs. IV’. G. Campbell and C. A. Waldron for their advice in preparation of the manuscript, to Mr. Willy Thomas for preparation of tissue for electron microscopy, to Mr. Richard Elkins for photography, and to Ms. Pamela Cohen for secretarial assistance.

Oral Surg. October, 1976 REFERENCES 1. Appelman,

2. 3. 4.

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