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Verrucous carcinoma—an enigmatic entity
Case Report
Verrucous carcinoma—an enigmatic entity Madhu Verma, MDS*, Jeevan Lata, MDS** *Senior Lecturer, Department of Oral & Maxillofacial Surgery, Gian Sagar Dental College and Hospital, Ramnagar, Rajpura, India, **Professor and Head, Department of Oral and Maxillofacial Surgery, Punjab Government Dental College and Hospital, Amritsar.
Abstract Verrucous carcinoma continues to be an enigmatic entity in the realms of maxillofacial pathology. It is a rare variant of well differentiated squamous cell carcinoma and has some unique characteristics clinically and histologically different from a typical oral squamous cell carcinoma. Verrucous carcinoma grows gradually, has a tendency of local invasion, and seldom metastasizes. Here we have reported 2 cases of verrucous carcinoma, in which surgical excision with wide normal margins was done. Pre-operative and postoperative biopsy results were compared and patients were followed up for maximum possible period. There was neither local recurrence nor distant metastasis observed. So, it is advised that surgical resection with sufficient safety margins should be done in such cases. Keywords: Ackermann’s tumor, cancer, oral cavity, tobacco, verrucous carcinoma
INTRODUCTION Verrucous carcinoma was first described as a distinct variant of well differentiated squamous cell carcinoma (WDSCC) by Ackermann in 1948.1 It represents 4.5–9% of oral squamous cell carcinoma, typically as a slowly enlarging gray or white warty, exophytic, superficially spreading, non-invasive and non-metastasizing growth.2 We encountered two cases of verrucous carcinoma of mandibular alveolar ridge and gingiva. This paper documents the management of verrucous carcinoma of mandibular alveolar ridge and gingiva and reviews the diagnosis and therapy of verrucous carcinoma.
chewing. There was no pain and the margins of the lesion were not indurated. Teeth in that dentoalveolar segment were not mobile. Regional lymph nodes were not enlarged. Left lateral oblique view of the mandible showed no underlying bony involvement (Figure 1). Pre-operative TNM classification was T2N0M0. The provisional diagnosis was made of verrucous carcinoma. Incisional biopsy was done and histopathological findings showed severe thickening of squamous epithelium with papillary proliferation and broad rete pegs. Swelling of nuclei and mitoses were found in some areas. The invasion into the basement membrane was not detected (Figure 2). After that, surgical excision of the lesion was done along with removal of dentoalveolar segment
CASE REPORT 1 A 34-year-old man reported to our department with the chief complaint of ulcer of the left lower posterior ridge and gingiva since one and a half month. He had history of tobacco chewing for the last 5–6 months. On examination, a papillary, sessile, ulcerated growth was present on the left lower alveolar ridge and gingiva extending from first premolar region up to the retromolar area, where he used to keep tobacco for
*Correspondence: Dr. Madhu Verma, Senior Lecturer, Department of Oral & Maxillofacial Surgery, Gian Sagar Dental College and Hospital, Ramnagar, Banur, H No. 1162, KSM Road, Gandhi colony, Rajpura Town, Patiala, Punjab–140401. E-mail: [email protected] Received: 26.04.2011 Accepted: 13.05.2011 © 2011 Indian Journal of Dentistry. Published by Elsevier Ltd.
Figure 1 Left lateral oblique view of mandible. 33
Verma and Lata
Figure 2 Incisional biopsy showed papillary proliferations with thickening of squamous epithelium and bulbous rete pegs, H & E staining.
Figure 5 Excisional biopsy again showed papillary proliferation with bulbous rete pegs. Basement membrane is intact, H & E staining.
Figure 3 Excision of lesion done with wide normal margins.
Figure 6 Postoperative photograph of the patient at 1 year follow-up examination.
He made an uneventful recovery (Figure 6). There was neither local recurrence nor distant metastasis observed postoperatively for 1 year. CASE REPORT 2
Figure 4 Removal of dentoalveolar segment containing teeth.
containing premolars and molars with safety margins of 5–10 mm (Figures 3 and 4). The specimen was sent for histopathological examination. Histopathological findings of the excisional biopsy were same as that of incisional biopsy (Figure 5). Histopathologically, it was diagnosed as verrucous carcinoma. 34
A 50-year-old man complained of swelling and pain in the lower anterior region for about 4 years. He was a chronic smoker and tobacco chewer for the last 5 years. There was an ulcerated, sessile, cauliflower like growth on the mandibular anterior gingiva and ridge (Figure 7). On palpation, the lesion was tender and margins were indurated. Lower central and lateral incisors were mobile. Regional lymph nodes were not palpable. Posteroanterior view of the mandible showed no underlying bony involvement. Pre-operative TNM classification was T1N0M0. The provisional diagnosis was made of verrucous carcinoma. Incisional biopsy was done and it showed papillary proliferation and severe thickening of squamous epithelium. Single cell keratinization and incomplete pearl formation were found occasionally. The basement membrane was partially missing (Figure 8). © Indian Journal of Dentistry 2011/Volume 2/Issue 2
Verrucous carcinoma—an enigmatic entity
Figure 7 Pre-operative photograph of patient showing cauliflower like growth.
Figure 10 Squamous keratin pearl formation. H & E staining at high magnification (original magnification 400×).
Figure 8 Incisional biopsy showing papillary proliferation and bulbous rete pegs.
Figure 11 Excisional biopsy showing sheets and nests of malignant cells of squamous epithelium, H & E staining at high magnification.
Figure 9 Lesion was excised and dentoalveolar segment removed.
The diagnosis was made of verrucous carcinoma. Later on, complete excision of the lesion was performed along with removal of dentoalveolar segment containing central and lateral incisors, with safety margins of 5–10 mm (Figure 9). The specimen was sent for histopathological examination. Histopathological findings of the specimen showed sheets and nests of the cells originating from squamous © Indian Journal of Dentistry 2011/Volume 2/Issue 2
Figure 12 Postoperative photograph after radiotherapy.
epithelium with cellular atypia and presence of numerous keratin pearls (Figures 10 and 11). Malignant cells were invading the connective tissue. Histopathologically, it was diagnosed as squamous cell carcinoma. Patient was sent for radiotherapy. After radiotherapy, he made a satisfactory recovery (Figure 12). There was neither recurrence nor distant metastasis observed for 1 year. 35
Verma and Lata
DISCUSSION Verrucous carcinoma is considered as a part of welldifferentiated squamous cell carcinoma and not a separate entity. Clinically, it presents as a wart-like exophytic growth. The classical histopathological features are an intact basement membrane, with preservation of stratification and broad rete pegs of carcinoma cells, which appear to punch into the underlying tissue.3 The oral cavity is one of the predilection sites for verrucous carcinoma. This carcinoma has also been reported in the nasal cavity, larynx, and esophagus. In the oral cavity, the buccal mucosa (60%) and lower gingiva (30%) is the common site.4 Most of the patients are elderly males (3:1) with an average age of 65 years (range 50–70 years) with history of tobacco chewing and smoking.2 Both the patients reported here were males with a history of tobacco chewing. Most common sites involved are lower gingiva and alveolar ridge. Regional lymph node metastases are exceedingly rare, and distant metastases have not been reported.5 None of our cases had lymph node involvement or distant metastasis. The histopathological diagnosis of verrucous carcinoma is sometimes deceptive because in some cases, superficial biopsies will show only hyperkeratosis, acanthosis, and benign papillomatosis. Deeper tissue biopsies are required for proper diagnosis. The most important pathological difference with squamous cell carcinoma is the good cytological differentiation throughout the tumor. Verrucous carcinoma can also be mistaken as a benign lesion histologically. There is also a problem of so called “hybrid” tumor involving both verrucous carcinoma and the usual squamous cell carcinoma. Thus, verrucous carcinoma can in turn lead to well differentiated squamous cell carcinoma. The close discussion between the clinicians and pathologists is necessary.5 In our case 2, first biopsy specimen was diagnosed as verrucous carcinoma and final biopsy report confirmed squamous cell carcinoma. So for exact diagnosis, sufficient volume of specimen, with enough surgical margins, is necessary when the verrucous carcinoma is excised. Recently, the role of human papilloma virus (HPV) and over expression of the p53 oncogene seems to be a significant etiological factor for verrucous carcinoma.6 But these two factors were not taken into consideration in our cases. Complete resection of the tumor is the best treatment for verrucous carcinoma. In almost all cases of verrucous carcinoma, neck dissection is not necessary because lymph node metastases are extremely rare.7 In both cases reported here, complete resection of the tumor with wide normal margins was done. Radiation therapy is not usually applied since it may change the nature of the tumor to a poorly differentiated squamous cell carcinoma. Some authors have reported that anaplastic transformation of verrucous carcinoma after
36
irradiation is not common and the radiosensitivity of verrucous carcinoma is usually good, therefore, radiotherapy can become a radical treatment for verrucous carcinoma.8 In case 1, fortunately, tumor was not so invasive. Resection with sufficient safety margins could be performed and therefore, we did not consider irradiation. But in case 2, since it was diagnosed as squamous cell carcinoma, along with excisional biopsy, additional radiotherapy was recommended. CONCLUSION For proper diagnosis of verrucous carcinoma, deeper tissue biopsies with adequate surgical margins are necessary since these may harbor the foci of well differentiated squamous cell carcinoma. In all cases of verrucous carcinoma, surgery should be done if the procedure has acceptable morbidity. Irradiation might be the second choice of treatment for verrucous carcinoma, where surgery could not be performed. The effectiveness of pre-operative chemotherapy for advanced verrucous carcinoma of the tongue has been reported.9 However, the effect of chemotherapy on verrucous carcinoma has not been thoroughly estimated at this moment in time. So, surgery is the first choice for the treatment of verrucous carcinoma and chemotherapy has only a complementary role to surgical procedure. REFERENCES 1. Ackerman LV. Verrucous carcinoma of the oral cavity. Surgery 1948; 23:670–8. 2. Spiro RH. Verrucous carcinoma, then and now. Am J Surg 1998;176: 393–7. 3. Jyothirmayi R, Sankaranarayanan R, Varghese C, Jacob R, Nair MK. Radiotherapy in the treatment of verrucous carcinoma of the oral cavity. Oral Oncol 1997;33:124–8. 4. Imai H, Yoshihara T. Verrucous carcinoma of the tongue; report of a case. Otolaryngology—Head and Neck Surgery (Tokyo) 1995;67: 1165–9. 5. Kawakami M, Yoshimura K, Hayashi I, Ito K, Hyo S. Verrucous carcinoma of the tongue—report of two cases. Bulletin of the Osaka Medical College 2004;50:19–22. 6. Lopez-Amado M, Garcia-Caballero T, Lozano-Ramirez A, LabellaCaballero T. Human papilloma virus and p53 oncoprotein in verrucous carcinoma of the larynx. J Laryngol Otol 1996;110:742–7. 7. Kato A, Takahashi Y, Yanohara K. Verrucous carcinoma of the tongue—a case report. Practica Oto Rhino Laryngologica 1991;84: 775–80. 8. Tharp ME II, Shidnia H. Radiotherapy in the treatment of verrucous carcinoma of the head and neck. Laryngoscope 1995;105:391–6. 9. Tanaka J, Yoshida K, Takahashi M, Suzuki M. A case of verrucous carcinoma of the tongue, effectively treated with pre-operative chemotherapy (UFT, CDDP, PEP) and irradiation. Gan To Kagaku Ryoho 1992;19:525–7.
© Indian Journal of Dentistry 2011/Volume 2/Issue 2
Verrucous carcinoma—an enigmatic entity Madhu Verma, MDS*, Jeevan Lata, MDS** *Senior Lecturer, Department of Oral & Maxillofacial Surgery, Gian Sagar Dental College and Hospital, Ramnagar, Rajpura, India, **Professor and Head, Department of Oral and Maxillofacial Surgery, Punjab Government Dental College and Hospital, Amritsar.
Abstract Verrucous carcinoma continues to be an enigmatic entity in the realms of maxillofacial pathology. It is a rare variant of well differentiated squamous cell carcinoma and has some unique characteristics clinically and histologically different from a typical oral squamous cell carcinoma. Verrucous carcinoma grows gradually, has a tendency of local invasion, and seldom metastasizes. Here we have reported 2 cases of verrucous carcinoma, in which surgical excision with wide normal margins was done. Pre-operative and postoperative biopsy results were compared and patients were followed up for maximum possible period. There was neither local recurrence nor distant metastasis observed. So, it is advised that surgical resection with sufficient safety margins should be done in such cases. Keywords: Ackermann’s tumor, cancer, oral cavity, tobacco, verrucous carcinoma
INTRODUCTION Verrucous carcinoma was first described as a distinct variant of well differentiated squamous cell carcinoma (WDSCC) by Ackermann in 1948.1 It represents 4.5–9% of oral squamous cell carcinoma, typically as a slowly enlarging gray or white warty, exophytic, superficially spreading, non-invasive and non-metastasizing growth.2 We encountered two cases of verrucous carcinoma of mandibular alveolar ridge and gingiva. This paper documents the management of verrucous carcinoma of mandibular alveolar ridge and gingiva and reviews the diagnosis and therapy of verrucous carcinoma.
chewing. There was no pain and the margins of the lesion were not indurated. Teeth in that dentoalveolar segment were not mobile. Regional lymph nodes were not enlarged. Left lateral oblique view of the mandible showed no underlying bony involvement (Figure 1). Pre-operative TNM classification was T2N0M0. The provisional diagnosis was made of verrucous carcinoma. Incisional biopsy was done and histopathological findings showed severe thickening of squamous epithelium with papillary proliferation and broad rete pegs. Swelling of nuclei and mitoses were found in some areas. The invasion into the basement membrane was not detected (Figure 2). After that, surgical excision of the lesion was done along with removal of dentoalveolar segment
CASE REPORT 1 A 34-year-old man reported to our department with the chief complaint of ulcer of the left lower posterior ridge and gingiva since one and a half month. He had history of tobacco chewing for the last 5–6 months. On examination, a papillary, sessile, ulcerated growth was present on the left lower alveolar ridge and gingiva extending from first premolar region up to the retromolar area, where he used to keep tobacco for
*Correspondence: Dr. Madhu Verma, Senior Lecturer, Department of Oral & Maxillofacial Surgery, Gian Sagar Dental College and Hospital, Ramnagar, Banur, H No. 1162, KSM Road, Gandhi colony, Rajpura Town, Patiala, Punjab–140401. E-mail: [email protected] Received: 26.04.2011 Accepted: 13.05.2011 © 2011 Indian Journal of Dentistry. Published by Elsevier Ltd.
Figure 1 Left lateral oblique view of mandible. 33
Verma and Lata
Figure 2 Incisional biopsy showed papillary proliferations with thickening of squamous epithelium and bulbous rete pegs, H & E staining.
Figure 5 Excisional biopsy again showed papillary proliferation with bulbous rete pegs. Basement membrane is intact, H & E staining.
Figure 3 Excision of lesion done with wide normal margins.
Figure 6 Postoperative photograph of the patient at 1 year follow-up examination.
He made an uneventful recovery (Figure 6). There was neither local recurrence nor distant metastasis observed postoperatively for 1 year. CASE REPORT 2
Figure 4 Removal of dentoalveolar segment containing teeth.
containing premolars and molars with safety margins of 5–10 mm (Figures 3 and 4). The specimen was sent for histopathological examination. Histopathological findings of the excisional biopsy were same as that of incisional biopsy (Figure 5). Histopathologically, it was diagnosed as verrucous carcinoma. 34
A 50-year-old man complained of swelling and pain in the lower anterior region for about 4 years. He was a chronic smoker and tobacco chewer for the last 5 years. There was an ulcerated, sessile, cauliflower like growth on the mandibular anterior gingiva and ridge (Figure 7). On palpation, the lesion was tender and margins were indurated. Lower central and lateral incisors were mobile. Regional lymph nodes were not palpable. Posteroanterior view of the mandible showed no underlying bony involvement. Pre-operative TNM classification was T1N0M0. The provisional diagnosis was made of verrucous carcinoma. Incisional biopsy was done and it showed papillary proliferation and severe thickening of squamous epithelium. Single cell keratinization and incomplete pearl formation were found occasionally. The basement membrane was partially missing (Figure 8). © Indian Journal of Dentistry 2011/Volume 2/Issue 2
Verrucous carcinoma—an enigmatic entity
Figure 7 Pre-operative photograph of patient showing cauliflower like growth.
Figure 10 Squamous keratin pearl formation. H & E staining at high magnification (original magnification 400×).
Figure 8 Incisional biopsy showing papillary proliferation and bulbous rete pegs.
Figure 11 Excisional biopsy showing sheets and nests of malignant cells of squamous epithelium, H & E staining at high magnification.
Figure 9 Lesion was excised and dentoalveolar segment removed.
The diagnosis was made of verrucous carcinoma. Later on, complete excision of the lesion was performed along with removal of dentoalveolar segment containing central and lateral incisors, with safety margins of 5–10 mm (Figure 9). The specimen was sent for histopathological examination. Histopathological findings of the specimen showed sheets and nests of the cells originating from squamous © Indian Journal of Dentistry 2011/Volume 2/Issue 2
Figure 12 Postoperative photograph after radiotherapy.
epithelium with cellular atypia and presence of numerous keratin pearls (Figures 10 and 11). Malignant cells were invading the connective tissue. Histopathologically, it was diagnosed as squamous cell carcinoma. Patient was sent for radiotherapy. After radiotherapy, he made a satisfactory recovery (Figure 12). There was neither recurrence nor distant metastasis observed for 1 year. 35
Verma and Lata
DISCUSSION Verrucous carcinoma is considered as a part of welldifferentiated squamous cell carcinoma and not a separate entity. Clinically, it presents as a wart-like exophytic growth. The classical histopathological features are an intact basement membrane, with preservation of stratification and broad rete pegs of carcinoma cells, which appear to punch into the underlying tissue.3 The oral cavity is one of the predilection sites for verrucous carcinoma. This carcinoma has also been reported in the nasal cavity, larynx, and esophagus. In the oral cavity, the buccal mucosa (60%) and lower gingiva (30%) is the common site.4 Most of the patients are elderly males (3:1) with an average age of 65 years (range 50–70 years) with history of tobacco chewing and smoking.2 Both the patients reported here were males with a history of tobacco chewing. Most common sites involved are lower gingiva and alveolar ridge. Regional lymph node metastases are exceedingly rare, and distant metastases have not been reported.5 None of our cases had lymph node involvement or distant metastasis. The histopathological diagnosis of verrucous carcinoma is sometimes deceptive because in some cases, superficial biopsies will show only hyperkeratosis, acanthosis, and benign papillomatosis. Deeper tissue biopsies are required for proper diagnosis. The most important pathological difference with squamous cell carcinoma is the good cytological differentiation throughout the tumor. Verrucous carcinoma can also be mistaken as a benign lesion histologically. There is also a problem of so called “hybrid” tumor involving both verrucous carcinoma and the usual squamous cell carcinoma. Thus, verrucous carcinoma can in turn lead to well differentiated squamous cell carcinoma. The close discussion between the clinicians and pathologists is necessary.5 In our case 2, first biopsy specimen was diagnosed as verrucous carcinoma and final biopsy report confirmed squamous cell carcinoma. So for exact diagnosis, sufficient volume of specimen, with enough surgical margins, is necessary when the verrucous carcinoma is excised. Recently, the role of human papilloma virus (HPV) and over expression of the p53 oncogene seems to be a significant etiological factor for verrucous carcinoma.6 But these two factors were not taken into consideration in our cases. Complete resection of the tumor is the best treatment for verrucous carcinoma. In almost all cases of verrucous carcinoma, neck dissection is not necessary because lymph node metastases are extremely rare.7 In both cases reported here, complete resection of the tumor with wide normal margins was done. Radiation therapy is not usually applied since it may change the nature of the tumor to a poorly differentiated squamous cell carcinoma. Some authors have reported that anaplastic transformation of verrucous carcinoma after
36
irradiation is not common and the radiosensitivity of verrucous carcinoma is usually good, therefore, radiotherapy can become a radical treatment for verrucous carcinoma.8 In case 1, fortunately, tumor was not so invasive. Resection with sufficient safety margins could be performed and therefore, we did not consider irradiation. But in case 2, since it was diagnosed as squamous cell carcinoma, along with excisional biopsy, additional radiotherapy was recommended. CONCLUSION For proper diagnosis of verrucous carcinoma, deeper tissue biopsies with adequate surgical margins are necessary since these may harbor the foci of well differentiated squamous cell carcinoma. In all cases of verrucous carcinoma, surgery should be done if the procedure has acceptable morbidity. Irradiation might be the second choice of treatment for verrucous carcinoma, where surgery could not be performed. The effectiveness of pre-operative chemotherapy for advanced verrucous carcinoma of the tongue has been reported.9 However, the effect of chemotherapy on verrucous carcinoma has not been thoroughly estimated at this moment in time. So, surgery is the first choice for the treatment of verrucous carcinoma and chemotherapy has only a complementary role to surgical procedure. REFERENCES 1. Ackerman LV. Verrucous carcinoma of the oral cavity. Surgery 1948; 23:670–8. 2. Spiro RH. Verrucous carcinoma, then and now. Am J Surg 1998;176: 393–7. 3. Jyothirmayi R, Sankaranarayanan R, Varghese C, Jacob R, Nair MK. Radiotherapy in the treatment of verrucous carcinoma of the oral cavity. Oral Oncol 1997;33:124–8. 4. Imai H, Yoshihara T. Verrucous carcinoma of the tongue; report of a case. Otolaryngology—Head and Neck Surgery (Tokyo) 1995;67: 1165–9. 5. Kawakami M, Yoshimura K, Hayashi I, Ito K, Hyo S. Verrucous carcinoma of the tongue—report of two cases. Bulletin of the Osaka Medical College 2004;50:19–22. 6. Lopez-Amado M, Garcia-Caballero T, Lozano-Ramirez A, LabellaCaballero T. Human papilloma virus and p53 oncoprotein in verrucous carcinoma of the larynx. J Laryngol Otol 1996;110:742–7. 7. Kato A, Takahashi Y, Yanohara K. Verrucous carcinoma of the tongue—a case report. Practica Oto Rhino Laryngologica 1991;84: 775–80. 8. Tharp ME II, Shidnia H. Radiotherapy in the treatment of verrucous carcinoma of the head and neck. Laryngoscope 1995;105:391–6. 9. Tanaka J, Yoshida K, Takahashi M, Suzuki M. A case of verrucous carcinoma of the tongue, effectively treated with pre-operative chemotherapy (UFT, CDDP, PEP) and irradiation. Gan To Kagaku Ryoho 1992;19:525–7.
© Indian Journal of Dentistry 2011/Volume 2/Issue 2