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Dermatopathology: Practical & Conceptual April - June 2003
Critique of an Enduring Concept: Metatypical Basal-Cell Carcinoma: An Analysis in Historical Perspective
Susan C. Kelly D.O.
Gürkan Kaya, M.D., Ph.D.
A. Bernard Ackerman, M.D.
Our Assessment of the Matter of Metatypical Basal-cell Carcinoma
-[Gr. meta after, beyond, over] 1. a prefix indicating (a) change, transformation, or exchange or (b) after or next."
(tip'i-kel) [Gr. typikos] presenting the distinctive features of any type."
Dorland's Illustrated Medical Dictionary,
29th ed., Philadelphia: W.B. Saunders Company, 2000:1093,1904.
(met.ah.tip.ik.al) Term used to describe tissue which is formed of elements identical to that normal for the site, but atypical in that the components are not arranged in the normal pattern [Gk meta, typos type.]"
Buttersworth Medical Dictionary
, 2nd edition, Boston: Buttersworth 1978:1057.
"There is a third type of malpighian epithelioma of which the clinical aspect is very similar to that of basal cell epithelioma, but which can show features of squamous cell epithelioma, a faster clinical course, extend eventually to lymph nodes and be resistant to doses of irradiation that cure the basal cell epitheliomas. In addition, this type does not entirely resemble squamous cell epitheliomas or the basal cell epitheliomas histologically. It can have a mixed constitution with a basal cell structure and squamous elements; or the cells which constitute it are neither typical nor atypical, but have intermediary characteristics. This epithelioma which, clinically and histologically, bears characteristics of neither the typical nor atypical epitheliomas, deserves to be called metatypical." Darier J, Ferrand M.
L'épithéliome pavimenteux mixte et intermédiaire. Forme métatypique du cancer malpighien de la peau et des orifices muqueux
[Mixed and intermediary stratified epithelioma. Metatypical form of the malpighian cancer of the skin and mucous orifices].
Ann de Dermat et de Syph
"The term 'basosquamous cell epithelioma' is used to designate the transitional forms that occur between basal cell and squamous cell epithelioma. I shall undertake to show that these transitional forms occur frequently, and that their prognosis is serious as compared with basal cell epithelioma." Montgomery H. Basal squamous cell epithelioma.
Arch Dermatol Syphil
" . . . the most important, because the most widely accepted, is the 'type intermédiaire mixte' [metatypical carcinoma] of Darier and Ferrand (1922) which is the 'basosquamous' form of Montgomery (1928). We can find no real criterion of the diagnosis of this type of rodent ulcer except the presence of the 'pearls' and these do not appear to be anything except our whorls in their higher grades." Lennox B, Wells AL. Differentiation in the rodent ulcer group of tumours.
Br J Cancer
"This conflict of opinion is also expressed in the works of reference on which the average clinical pathologist has to rely when faced with a doubtful section. Thus Ackerman (1953) says that 'practically all lesions diagnosed as baso-squamous carcinoma are basal-cell carcinoma and behave as such.' Essentially similar are the views of Lever (1949, 1954), Evans (1956), and Allen (1953, 1957), who state that the appearances usually interpreted as baso-squamous cell carcinoma are simply areas of keratinization in basal-cell carcinomata and are of no prognostic significance." Burston J, Clay RD. The problems of histological diagnosis in baso-squamous cell carcinoma of the skin.
J Clin Pathol 1959; 12; 73.
"In 1928, Montgomery described a type of basal cell carcinoma of the skin that he thought differed from typical basal cell carcinoma both in its histologic appearance and biologic behavior. Since that time, there has been considerable debate over the validity of Montgomery's conclusions. This controversy spans four decades and includes a wide spectrum of differing opinions. The few studies dealing with the identity of basosquamous cell carcinoma suffer from small numbers of cases and from relatively short follow up periods." Borel DM. Cutaneous Basosquamous carcinoma: review of the literature and report of 35 cases.
"We suggest to name the tumor of this report a basal cell carcinoma with areas of intermediate differentiation, but not metatypical carcinoma, which has not been precisely defined. Further research is required in order to know if the shorter and better name of baso-intermediary carcinoma can be used. Identification of the intermediate differentiation pattern in a BCC [basal-cell carcinoma] is important, because this tumor is more malignant in comparison with the common BCC pattern, as suggested by the statistical data." Lopes de Faria, Nunes PHF. The histopathology of the skin basal cell carcinoma with areas of intermediate differentiation: A metatypical carcinoma?
Path Res Pract
"Basal Cell Carcinoma With Squamous Metaplasia (Basosquamous or Metatypical Carcinoma) This is primarily a histologic variant of BCC, and there are usually no clinical features that allow one to make the diagnosis preoperatively. Although the matter is controversial, some authors consider this a distinct entity that biologically behaves more like a SCC [squamous-cell carcinoma] than a BCC. These authors think that this variant of BCC is much more aggressive and destructive in its behavior, more likely to metastasize, and more likely to recur after treatment. Some authors have suggested that prior irradiation predisposes to the development of this neoplasm, although this has been disputed. Others have observed recurrent BCCs to acquire a more metatypical histologic appearance with each subsequent recurrence. It has been estimated that metatypical basal cell carcinoma constitutes 1 to 2.5 percent of all nonmelanoma skin cancer. When metastases occur with this variant of BCC, they may have the same microscopic appearance as the original tumor or may resemble a poorly differentiated SCC. The fact that some metastatic metatypical basal cell carcinomas may have the histologic features of a SCC is in keeping with Fidler's concept that tumors with metastatic potential consist of a heterogenous population of cells, some with a greater potential for metastases than others. Thus, the more squamoid cells in a metatypical BCC would have a greater potential for metastases and could give rise to a histologic picture of SCC in the seeded tissue. The incidence of metastases with this variant of BCC has been estimated to be 9.7 percent." Lang P, Maize J. Basal Cell Carcinoma. In: Friedman RJ, Rigel DS, Kopf AW,
Cancer of the Skin.
W.B. Saunders: Philadelphia; 1991:4445.
This subtype of basal-cell carcinoma has been the source of some confusion regarding its histologic feature. It is probably best to use this designation when evaluating a basal cell carcinoma with features intermittent [sic] between a nodular basal cell carcinoma and a squamous cell carcinoma. These tumors have basaloid cells with variable eosinophilic features, prominent mitotic activity, and numerous apoptotic cells . . . Peripheral palisading and stromal retraction are rare to absent. Nuclei are enlarged and some spindling of cells may be appreciated. Premature cornification is common. Keratin pearls occasionally are seen. These tumors tend to be more aggressive with a greater incidence of perineural and lymphatic spread. They may grow with the speed of squamous-cell carcinomas and have clinical features of both tumor types.
The diagnosis of basosquamous basal cell carcinoma is most appropriately used when evaluating a tumor with contiguous areas of basal-cell carcinoma and squamous-cell carcinoma. The typical features of both tumor types are present with a minimal intermediate area of blending between the two. The term 'mixed carcinoma of the skin' has been used when no intermediate tumor cells are present. Some authors have applied this term to so-called 'collision'
tumors, that is, basal-cell carcinoma colliding with squamous cell carcinoma. The term has also been used perhaps in a similar way for metatypical BCC, to identify tumors intermediate to
BCC and SCC throughout the neoplasm. Given the disparate uses of this term it is perhaps best that it be abandoned or strictly defined." Boyd AS. Tumors of the epidermis. In: Barnhill RL, Crowson AN, Busam KJ, Granter SR (eds).
Textbook of Dermatopathology.
New York: McGraw-Hill, 1998:5167.
There is some controversy in the literature on BCC as to which tumors of this type should be classified as 'basosquamous.' Some authors include cases that show a gradual transition between basaloid elements and cell nests with more abundant eosinophilic cytoplasm, larger nuclei, and a concentric arrangement ('pearls'), whereas others restrict the term to lesions with distinct but admixed components of BCC and overt squamous carcinoma. The squamous carcinomatous element of basosquamous carcinoma should demonstrate nuclear anaplasia, dyskeratosis, nucleolar prominence, and mitotic activity to avoid confusion with areas of simple squamous metaplasia in BCC. The basocellular component of such neoplasms may exhibit nodulocystic, adenoid, superficial, infiltrative growth patterns. This variant of BCC is quite rare (less than 0.5% of all cases), if the foregoing criteria are observed.
Similarly, 'metatypical' BCC has been defined in various fashions by several authors, this term is intended to describe variants of basal cell carcinoma that lack peripheral palisading within cellular lobules, have larger nuclei and more abundant eosinophilic cytoplasm, and display a bluntly spindle cell growth pattern with focally prominent intercellular bridges. Cell nests are more elongated than those in nodulocystic BCC, and the stroma is variably fibroblastic. Hence, metatypical BCC integrates certain of the features of the infiltrative and adamantinoid subtypes; in addition, DeFaria has suggested that metatypical BCC is cytologically intermediate to nodulocystic BCC and squamous carcinoma. Perineural and lymphatic permeation is seen more commonly in cases of metatypical BCC, relative to other variants." Maize JC, Burgdorf WH, Hurt MA,
et al. Cutaneous Pathology.
London: Churchill Livingstone, 1998:457.
"In summary, in each individual tumor, genetic analysis of different areas showed entirely concordant changes. Furthermore, the genetic changes were consistent with the BCC genotype, whereas characteristic genetic changes of squamous neoplasia were not observed in areas of either BCC or squamous cells. These results suggest that the areas of squamous cell represent squamous differentiation of BCC or BCC precursor cells rather than independent areas of squamous neoplasia. Based on genetic analysis, these results strongly indicate that BCC may focally develop into areas of pure squamous morphology. The results are of particular interest, since BCC have been reported with areas of malignant squamous cells, so-called basoquamous carcinoma; however, the existence of basosquamous carcinoma as a separate entity is controversial. Using tissue microdissection in a larger number of controversial cases may eventually clarify whether morphologic tumor heterogeneity is associated with concordant, progressive, or diverse genetic changes. In tumors in which the differentiation of SCC and BCC is difficult based on histologic examination only and is of clinical or investigative importance, microdissection of different tumor components with subsequent genetic analysis may prove to be a useful diagnostic tool in the future." Boni R, Vortmeyer AO, Stern JB,
Concordance of genetic changes in basal cell carcinoma and associated clusters of squamous cells.
J Invest Dermatol
1998; 111, 173174.
"In conclusion, cornifying (keratotic), bowenoid, and squamoid expressions of basal-cell carcinoma are simply histopathologic variants of basal-cell carcinoma, not something different, to wit, basosquamous carcinoma. In our estimation, basal-cell carcinoma and squamous-cell carcinoma are separate and distinct carcinomas, as separate and distinct, for example, as adenoid-cystic carcinoma, neuroendocrine carcinoma, and matrical carcinoma. The finding of squamoid cells in a basal-cell carcinoma does not alter the basic character of that carcinoma. It is still a basal-cell carcinoma, and not a squamous-cell carcinoma or a basosquamous carcinoma. A squamous-cell carcinoma made up of cells with small, crowded nuclei and scant cytoplasm is still a squamous-cell carcinoma." Ackerman AB, Reddy VB, Soyer HP.
Neoplasms with Follicular Differentiation,
New York: Ardor Scribendi, 2001:985.
For more than 80 years, dermatologists and pathologists, including dermatopathologists, have used the term "metatypical" for a type of basal-cell carcinoma that exhibits some "squamous features" and, following the lead of Darier and Ferrand in 1922, have designated that neoplasm "metatypical basal-cell carcinoma." Sad to say, until this day, the word metatypical has yet to be defined in a comprehensible, lucid, repeatable way and the concept of metatypical basal-cell carcinoma has yet to be characterized in an understandable, meaningful, dependable manner.
In actuality, no small number of pathologists and dermatologists have addressed the subject of metatypical basal-cell carcinoma, but hardly any of them have made an effort to define the term "metatypical." What follows are some examples of this deficiency:
"Basosquamous (metatypical) carcinoma has the general configuration of a basal cell, but it also contains atypical squamous cells. This variant is more aggressive than the conventional basal cell carcinoma, a high proportion of the metastasizing basal cell tumors belong to this type, which should be distinguished from the keratotic form of basal cell carcinoma." Rosai J (ed.).
Ackerman's Surgical Pathology,
8th ed. Philadelphia: Mosby 1996:117118.
"Several authors have accepted the existence of basal squamous cell epitheliomas or metatypical epitheliomas. They are considered by some to represent a transition from basal cell carcinoma to squamous cell carcinoma. It has been stated that a continuum extends from basal cell carcinoma at one extreme to squamous cell carcinoma at the other. The incidence of basal squamous cell carcinomas among basal cell carcinomas has been judged to be 3%, 8%, and even 12%. It has also been stated that basal squamous cell epitheliomas show a greater tendency to metastasize than basal cell carcinoma. However, the existence of basal squamous cell epitheliomas is questioned by many. It would seem that the entirely different genesis of squamous cell carcinoma, a true anaplastic carcinoma of the epidermis, and basal cell carcinoma, a tumor composed of immature rather than anaplastic cells, makes the occurrence of transitional forms quite unlikely. It can be assumed that the so-called mixed type of basal squamous cell epithelioma represents a keratotic basal cell carcinoma . . . and that the intermediate type represents a basal cell carcinoma with differentiation into two types of cells. Other putative examples of basosquamous differentiation are better interpreted as basal cell carcinoma with follicular differentiation. . . ." Kirkham N. Tumors and cysts of the epidermis. In: Elder D, Elenitsas D, Jaworsky F, Johnson B Jr, (eds.)
Lever's Histopathology of the Skin,
8th ed. Philadelphia: Lippincott-Raven, 1997;72829.
"Morphoeiform, metatypical, and infiltrative variants [of basal-cell carcinoma] have the highest recurrence rates." Mckee PH,
Essential Skin Pathology with Clinical Correlations, 2nd ed.
Barcelona, Spain: Mosby-Wolfe, 1997:15.34.
"Metatypical Basal Cell Carcinoma
Synonyms. Keratinizing basal cell carcinoma, basosquamous carcinoma,
epithélioma pavimentaux métatypique mixte
(DARIER and FERRAND 1922),
epithélioma pavimentaux intermédiaire
(DARIER). Considering how rare these basal cell carcinoma variants are, it is unfortunate that so much has been written about them and so many names proposed. The issues are: What diagnosis should one make when a tumor shows microscopic differentiation towards both a basal cell carcinoma and squamous cell carcinoma and does this have clinical significance? We see several possibilities:
Collision Tumor. Since both basal cell carcinoma and squamous cell carcinoma are common and arise in sunlight-damaged skin, it is not surprising that two independent tumors should collide. Histologically one sees two distinct types of cells that abut or mingle slightly.
Keratotic Basal Cell Carcinoma
(epithélioma pavimentaux métatypique mixte).
Since some basal cell carcinomas have a follicular origin, it seems logical that some show keratinizaton. Such tumors do not differ clinically from ordinary basal cell carcinomas.
Adenoid Squamous Cell Carcinoma. Some tumors have a glandular pattern but otherwise fulfill the histologic and immunohistochemical criteria for squamous cell carcinoma. They are easily confused with an adenoid basal cell carcinoma and maybe viewed as overlap tumors.
Metatypical Basal Cell Carcinoma
(epithélioma pavimentaux intermédiaire).
This variant is perhaps a unique tumor, but it is very rare and may simply be a subset of basal cell carcinoma that is radiation-resistant. Under the microscope one cannot differentiate between a poorly differentiated basal cell carcinoma and squamous cell carcinoma. Clinically they tend to be large aggressive tumors that usually have been successfully irradiated. For that reason they have become less common as more basal cell carcinomas are treated surgically. Two typical locations are the back and the nose. Almost all true metastatic basal cell carcinomas arise from this type." Braun-Falco O, Plewig G, Wolf HH, Burgdof WHC.
2nd ed. Berlin Heidelberg, New York: Springer-Verlag, 2000:1480.
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