Verrucous Carcinoma, Then and Now

PRESIDENTIAL ADDRESS Verrucous Carcinoma, Then and Now

Ronald H. Spiro, MD, New York, New York

The salient clinical and pathological features of verrucous carcinoma. as first described by Ack- erman In 1948, are reviewed. Two case reports are presented. The first concerns a personal ex- perience with a patient who had five surgical procedures for multifocal oral verrucous carcinoma and remains alive and well 28 years after her initial treatment. The second report high- lights the remarkable story of President Grover Cleveland's secret surgery for verrucous carcinoma of the palate In 1893. Current concepts about the management of this uncommon tumor are reviewed, as well as some recent Investiga- tions that deal with its etiology. Am J Surg. 1998; 176:000-000. (l:) 1998 by Excerpta Medica, Inc.

iftyyears have passed since Lauren V. Ackerman 1 first used the term "verrucous carcinomaU (VC) to de- Fscribe an unusual and indolent variant of oral squamous carcinoma (SeC). His observations were based on 26 men and 5 women who received treatment for this unusual tumor during hi~ years as a pathologist at Ellis Fishel State Cancer in Columbus, Missouri. Tobacco chewing seemed to be a significant etiologic factor In what subsequently came to be known as Ackerman's tumor. Aged men were most often afflicted in his series, and most of the tumors Although Ackerman's original repon In 1948 long amt..', involved the cheek mucosa (18 patients) or the lower gum datt..'s contemporary staging and offered few clinical details, (8 patients).' many of the tumors he described had to be sizeable. Eleven Grossly, these lesions were rather sparsely described as of his 31 patients required a composite resection, and the "pebbly, mamillated" in appearance, or "piled up in olgal tumor was considered too extensive for surgery. in 2 others. folds with deep clefrlike SP"lCCS between them .... " Micro, To this day, biopsy errors arc common, and dday in diag. scopic features included prominent surface keratin, dm.;n, nosis remains a problem. Even \vith a good tissue sample growth of club-shaped fingers of hyperplastic epithelium that includes the interface of the tumor with the host, the that push, rather than infiltrate, deeply toward an intact diagnosis of carcinoma may still prove elusive because the basement membrane, and a prominent inflammatory reae, epithelial component of these tumors is so well differenti~ tion in the adjacent tissues. ated and the basement membrane remains intact. Extension of the tumor along the surface was typical in In his discussion of treatment options, Ackennan ex~ these patients. Cheek mucosal lesions, for instance, would pressed a clear preference for surgery, a view shared by most extend into the sulci and cv(.'ntually destroy bone. Some of head and neck oncologists today. Although local recur~ thcse tumors even reached the cutaneous surface of the renee was noted in 8 of 14 patients (57%) who received cheek or involved the external aspect of the oral commis- r

CASE REPORT the Sherman Silver Act of 1890, a major contributory A 58'year~old Cuban woman gave a 7-week history of factor to what was later called "the panic of'93," there had palate irritation when she came to my office in June 1969 been a major shift from gold to silver. The 53rJ. Congress with a white, warty lesion of the left hatd palate. She had had failed to enact remedial legislation. With US gold been a 3-pack.pcr-day smoker, and biopsy elsewhere had reserves at a dangerous low, world confidence in the Amer. been read as epidermoid carcinoma. The lesion extended iean economy was crumbling. The need for strong leader- from the left upper bicuspid region to the tuberosity and ship from the White House was obvioll.'S. reached the midline. There was no cervical adenopathy. The time could not have been worse for a presidential Treatment consisted of a peroral partial maxillectomy health crisis.' During a social call at the White House, with split thickness skin graft, and the p:uhology report Major Robl'tt M. O'Reilly, Cleveland's physician, was described a sec that infiltrated hone. (Material not avail. asked to examine a "rough place" in the roof of the presi- able for review.) She did well With a demal obturator until dent's mouch that had been present for 4 or 5 weeks. October 1983, more than 14 years after her initial surgery, Concerned by what he saw, scrapings were taken and werc when a left lower molar tooth became loose. On examina. examined anonymously by a pathologist ,H the Army Med~ tion, there was a 2.5.cm warty tumor in the left lower ical Museum (now the Armed Forces Institute of Pathol~ gingiva extending from the retromolar to the premolar ogy), who thought the diagnosis was probably "epithelio~ area~ Pseudoepitheliomatous hyperplasia was favored on rna." At this point, Dr. joseph Decateur Bryant, a New biopsy, but VC could not be excluded. A composite resec. York City surgeon and personal friend of the president, was tion was performed in conjunction with left supraomohy- summoned. On examination 4 days later, he visualized a oid neck dissection. VC was the final diagnosis, with in.situ quarter~sized, ovoid, ulcerated lesion on the left hard palate carcinoma involving one lateral margin. All excised lymph extending from the inner surface of the molar teeth to nodes were negative. within one~third inch of the midline, slightly overlapping In January 1984, more than 10 yeats later, at the age of the soft palate. A second biopsy, read at johns Hopkins 83, a new I5-mm lesion appeared in the left cheek mucosa Hospital, confirmed the diagnosis of "epithelial carCll1o~ not far from the scar of the previous composite re~cction. rna Peroral resection again confirmed the diagnosis of sec, Cleveland reluctantly proposed a July 1 date for surgery but it was not clear \vhether this was a recurrence or another primary. provided it could be performed withom public disclosure of Four months later, peroral resection of a l~cm nodule his illness. All agreed that any suspicion of presidential within the substance of the left cheek anterior to the last infirmity might aggravate the panic and propel the nation excision yielded metastatic SCC in fibroadipose tissue, toward bankruptcy. It was his idea to arrange for the use of presumably a lymph node teplrtcl'd hv rumor. Two monrh~ the yacht Oneida, owned hv his coad friend Commndore later, she required a left subtotal parotidectomy tor a 2-cm E!l,.~Sl.:!lcJ!\.l, '.\L.~... \.:~... .'.~: periparotid lymph nooe metastasis. Adjunctive radiation the East River. With political concerns foremost in his therapy was considered at this point, but was not thought mind, Cleveland was reassured that he would be able to to be feasible. appear at a special session of Congress that he would In November 1994, 5 months later, a new nooule ap~ convene on August 7th for the purpose of repealing the peared in the soft tissue overlying the body of the left Sherman Act. The stated purpose of his trip was to be rest mandible, apparently a metastatasis in a lymph node adja~ and relaxation at Gray Gables, the president's summer cent to the facial artery. This was confirmed by needle home on Buzzard's Bay in Massachusetts. biopsy, and treatment conslste. d 0f a permanent I'" Im~. The high drama associated with Cleveland's surgery in a plant. The patient had no sign of residual or recurrent makeshift operating room on the yacht Oneida while cruis~ tumor when last sel'n 3 years later at the age of 86, 28 years ing up the East River has been told and retold. In addition after her initial procedure. to Drs. O'Reilly and Bryant, the team consisted of Dr. An important lesson to be learned from the above case William Keen, eminent professor of surgery from Jefferson history is that prolonged follow-up may be necessary to College, Dr. John Erdmann, Bryant's assistant, Dr. Edward appreciate the potential for multicentricity in patit:nts with janeway, a prominent New York internist, and Dr. Ferdi- VC. This raises an interesting thought about another, nand Hasbrouck, a New York dentist skilled in the usc of high-profile patient-arguably one of the most fascinaring nitrous oxide. case histories in the lexicon of canct:r rreatment-who One half hour pasc nonn on july 1st, ns the Oneida cnJised died of other causes 15 years after presumably successful up the East River at half speed, the president was posi- treatment of what, in retrospect, was VC of the upper tioned in a chair, nitrous oxide anesthesia was induced, and jaw.3~6 both left upper premolar teeth were extracted. Peroral exposure was enhnncco by a special cheek retractor that CASE REPORT Keene had bought in Paris some years previously (now The year was 1893, and Gruver Cleveland, the 22nd and standard equipment). After topical application and injec~ the 24th president of the United States (and the only tion of cocaine, an incision was made through gingival and president to serve two nonconsecutive rerms) was facing a palate mucosa to the underlying bone. Supplemental ether crucial personal and political challenge. It was only a few inhalation was then used to facilitate a partial maxillec. months into his second term, and the nation's economy tomy, including the left upper alveolus from the first bi~ was deteriorating sharply. Unemployment was high, banks cuspid to just behind the last molar tooth, the hard palate were closing, and export volume was shrinking. Following to the midline, and a small portion of the soft palate.

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Onlyat this point was it appreciated that the tumor had either an official pathology report or the original slides and extended into the antrum, involving the floor around the blocks. In the new sections, however, the mucosal surface roots of the molar teeth. For this reason, the remaining left was "teplaced abruptly by sheets of epithelial cells which maxilla, exclusive of medial wall and infraorbital plate, was projected above the surface of the mucosa in papillary apparently removed in piecemeal fashion, and the cavity fronds corresponding to the wart~like growths apparent was packed with iodofonn gauze. The 1 hour and 20 grossly. In the submucosa, elongated ... club.shaped epi~ minute procedure was well tolerated. Hemostasis had been thelial sheets could be seen to infiltrate." There was no achieved with pressure, hot water, and at one point, gal~ doubt that Cleveland's lesion fulfilled all of Ackerman's vanocautery. It was Keen's estimate that the blood loss was criteria for VC.5 "probably about 6 ounces." Recovery was tematkably uneventful, and official Wash. CURRENT STATUS ington was oblivious to what had transpired when Cleve- For more than 2 decades after his paper appeared, tumors land debatked from the yacht 4 days latet (july 5th) and that fit Ackerman's description were reported in the liter~ walked to his waterfront residence. The secrecy was pre~ ature under a variety of names, including florid papilloma. served when, on July 17th, he rejoined the surgical team on tosis, oral florid verrucosis, verruca acuminata, vemlcous board the Oneida for a second procedure to remove some squamous cell carcinoma, and papillomatoses mucosae car~ "suspicious tissue" noted by Bryant on examination a week cinoides. By the 1970s, they were consistently termed after the first operation. The two procedures had proouced "verrucous carcinoma" or "Ackennan's tumor," and it was a defect of 2.5 by 13{16 inches, but relatively normal clear that this uncommon lesion could arise in other areas speech was restored by a vulcanized rubber prosthesis fab~ of the body. Reported sites of origin include skin, male and ricated by Dr. Kasson Gibson, a New York dentist-so female genitalia, anal canal, uterine cervix, bladder and much so that members of Congress were unaware of any renal pelvis, and esophagus. By the early 1980s, more than change in Cleveland's voice when he addressed the special 400 cases of VC had been reported, an obvious reflection of session on two occasions. His efforts were largely respon- considerable clinical interest. 7 sible fot repeal of the Silver Act that October and the With respect to the upper aerodigestive tract, where these gradual restoration of fiscal stabiliry. tumors most often arise, the oral cavity remains the most common site of origin. The incidence is highest in the Cleveland remained in relatively good health until late in check muco.sa, gingivae, and retromolar areas. Glottic lar- his retirement, when he developed gastrointestincancers).s good cigars. In unpublished notes, Hayes Martin expressed Diagnosis continues to be a problem. In a 1980 study, admiration for the "skill and the courage," as well as the Shear and Pindborg9 emphasized that verrucous hyperpla- good fortune of the surgical team. An operation that often sia is clinically indistinguishable from verrucous carcinoma involves significant blood loss \\'as swiftly perfonned with- withOlu careful histologic examination. According to out endotracheal intubation. Recovery was rapid and un~ them, carcinoma is characterized by extension of the lesion eventful, and the tumor was controlled. Keen) himself into the underlying connective tissue deep to the adjaccnt reflected that "the operation itself was as nothing compared normal epithelium. They believed that both lesions can with scores that both of us [Bryant and Keen] had per- exist concurrently, leukoplakia, apparently leaked by Hasbrouck, which was promptly de- which can in tum lead to VC and then invasive carci- nied by his physicians and the White House. Reassured by noma. Emphasizing that clinical and histologic diagnosis his reappearance in apparent good health, the American can be difficult, these authors cite pseudocpitheliomatous public remained in the dark until 1917, when Keen} re~ hyperplasia, well-differentiated squamous carcmoma, counted the entire escapade. chronic candidiasis, and condyloma accuminatum as le- Additional details have emerged in subsequent publica- sions that must be distinguisht.'d from VC. This distinction tions, especially that of Morreels4 in 1967, but there was no obviously requires concurrence between the clinician's ap~ resolution of the confusion in diagnosis until Brooks et at,5 preciation of the typical verrucous appearance of the tumor pathologists at Jefferson Medical School, finally obtained and the pathologist's identification of the microscopic cri~ penn ission to prepare additional sections from what re~ teria described by Ackcrman. mained of the surgical specimen and reported their results Treatment recommendations have not changed apprecia- In 1980. Recalling that Cleveland's palate lesion had ini. bly since Ackerman originally advised radiotherapy (RT) tially been called "epithelioma," and later "sarcoma" by for the small, superficial lesion and surgery "if at all exten~ Keene because of the fleshy character of the tumor within sive." Early enthusiasm for RT waned after the report of the antrum, they were unsuccessful in their attempts to find Demian and otherslO that transformation to a more ana~

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plastic tumor type occurred in about 30% of patients who his death in 1993, he was recognized as a pathologist's received curative doses of RT for VC. For the larynx in pathologist. Several of his trainees nm". occupy positions of panicular, it was also belil:ved that yes were radioresis- leadership in prestigious medical centers throughout the tant. Although most clinicians still prefer resection when country. No matter that the entity he so well characterized feasible, more recent studies suggest that the radiorespon- in 1948 had actually been the subject of a case report siveness and treatment results are quite similar when low. published in 1941 by Friedell and Rosenthal" describing a 1 2 stage yes are compared with similar SCCs. 1.l patient with "papillary verrucoid carcinoma." Ackerman Early concerns about "malignant transformation" associ. still deserves credit for accurately describing and focusing ared with RT have nO[ been substantiated in more recent attention on this uncommon neoplasm. To this day, it reports. This anaplastic evolution may relate to "hidden" remains a challenge in clinical management as well as a areas oflesser differentiation within the tumor, hut it is also provoccttive model for cell biologists in search of a better likely that at least some of the reponed patients whose understanding of oral carcinogenesis. tumors "transformed" did not, in fact, have VC. \Vhatever I wish to thank the members of the Society of Head and the explanation, other studies indicate that similar trans, Neck Surgeons for the honor of serving as your president 1J 15 formation can occur in surgically treated patients. - during this momentous year. Unification of the two na- From the outset, it has been clear that tobacco plays a tional head and neck societies has been a remarkable significant role in the pathogenesis of VC. More than one achievement. 1 believe this ecuminism heralds a new era in third of the patients in Ackerman's original report were which physicians of different disciplines and nationalities tobacco chewers, and the relationship between smokeless will receive better support in their efforts to expand our tobacco and verrucoid oral lesions has been established in knowledge and improve treatment in head and neck on, several other studies. The habitual chewing of "pan," a cology. mixture of betel leaf, lime, betal nuts, and tobacco, has long been implicatc-d in the high incidence of verrucous, type oral cancers in IndiaY' As Ferlito and Rccher17 REFERENCES pointed out years ago, however, tobacco usage is not a 1. Ackerman LV. Verrucous carcinoma of the oral cavity. 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The final diagnosis of southern blot hybridization or immunochistochemistry President Cleveland's lesion. Transactions & Studiesof the CoUege of (which arc less sensitive), HPV DNA was identified in up Physicians of Philadelphia. 1980;2,1-25. l8 to 85% of a cohort of patients with laryngeal ve Thus 6. BaBe( AJ. Grover Cleveland's secret cancer. Res Staff Phys. far, it is far from clear that HPV plays a specific role in the 1979;2537-40. genesis of VC. Depending on the sensitivity of the assay 7. Tomes K, Bang G, Koppang HS, Pederson KN. Oral verrucous and whether frozen or paraffin'embedded tissue is studied, carcinoma. 1m] Oral Surg. 1985;14:485-492. the yield of HPV DNA seems to be similar in squamous 8. RaJenJran R, Sugathan CK, Augustine J, et al. Ackerman's and VC, and it is also present to a lesser extent in normal tumor (verrucous carcinoma) of the oral cavity: a histopathologic oral mucosa, benign leukoplakia, and intraepithelial neo~ study of 426 cases. 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