The Kaiser's cancer revisited: was Virchow totally wrong?

On 15 June 1888, the German Emperor, Kaiser Friedrich III, died of laryngeal cancer. Three biopsies of his laryngeal lesion had been taken by the British laryngologist, Morel Mackenzie, in 1887 and diagnosed by Rudolf Virchow as “pachydermia verrucosa laryngis”, confirming Mackenzie's assessment that the Kaiser's disease was benign. A fourth specimen coughed up by the patient was considered by Virchow to be nondiagnostic. A further specimen expectorated by the patient 3 months before his death was diagnosed as carcinoma by Wilhelm Waldeyer. The autopsy revealed squamous carcinoma in the larynx with a cervical lymph node metastasis. The discrepancies between the initial diagnoses and the final outcome of the Kaiser's disease gave rise to a never-ending medical controversy. Our investigations on this historical case were limited to the official German documents and publications and their English translations and to subsequent literature sources of the time, after having received confirmation that the histological slides and Virchow's original reports had been lost. Based on current surgical pathology knowledge, we propose that the tumour that challenged the diagnostic skills of the founder of pathology was hybrid verrucous carcinoma (HVC), an extremely rare, metastasizing variant of verrucous carcinoma (VC) composed of pure VC mixed with clusters of conventional squamous cell carcinoma. As we see it now, Virchow was therefore not totally wrong. Our retrospective evaluation suggests that Virchow's detailed description of the Kaiser's cancer preceded the paper that contributed to the full understanding of HVC of the larynx by 110 years.

[1]  F. Bosman Advances in Pathology , 1942, Revue medicale suisse.

[2]  L. Michaels,et al.  Image analysis in the discrimination of verrucous carcinoma and squamous papilloma , 1992, The Journal of pathology.

[3]  J. Medina,et al.  Verrucous-squamous carcinomas of the oral cavity. A clinicopathologic study of 104 cases. , 1984, Archives of otolaryngology.

[4]  C. Muro-Cacho,et al.  Expression of Transforming Growth Factor β Type II Receptors in Head and Neck Squamous Cell Carcinoma , 1999 .

[5]  Theodore H. Schwann,et al.  Microscopical researches into the accordance in the structure and growth of animals and plants , 1847 .

[6]  N. Gale,et al.  Benign and Potentially Malignant Lesions of the Squamous Epithelium and Squamous Cell Carcinoma , 2006 .

[7]  C. Morales Angulo,et al.  [Verrucous carcinoma of the larynx]. , 1995, Acta otorrinolaringologica espanola.

[8]  P. Slootweg,et al.  Verrucous hyperplasia or verrucous carcinoma. An analysis of 27 patients. , 1983, Journal of maxillofacial surgery.

[9]  R. J. Cullen,et al.  Verrucous carcinoma of the larynx. , 1982, Clinical otolaryngology and allied sciences.

[10]  R. Laurenson The Emperor who smoked a pipe , 1995, The Journal of Laryngology & Otology.

[11]  M. Mackenzie The Fatal Illness of Frederick the Noble , 1888, Edinburgh Medical Journal.

[12]  L. Barnes,et al.  Pathology and genetics of head and neck tumours , 2005 .

[13]  D. Trask,et al.  National survey of head and neck verrucous carcinoma , 2001, Cancer.

[14]  J. Lin Virchow's pathological reports on Frederick III's cancer. , 1984, The New England journal of medicine.

[15]  Jacques Ferlay,et al.  Estimating the world cancer burden: Globocan 2000 , 2001, International journal of cancer.

[16]  Prof. Dr. Waldeyer Die Entwicklung der Carcinome , 1867, Archiv für pathologische Anatomie und Physiologie und für klinische Medicin.

[17]  A. Seymour Histological Typing of Tumours of the Upper Respiratory Tract and Ear , 1991 .

[18]  J. Freeman,et al.  Laryngeal verrucous carcinoma: A clinicopathologic study and detection of human papillomavirus using polymerase chain reaction , 1994, The Laryngoscope.

[19]  G. Pack,et al.  Historical Case Records of Cancer: The Laryngeal Cancer of Frederick III of Germany , 1940, Annals of medical history.

[20]  R. Fechner A Brief History of Head and Neck Pathology , 2002, Modern Pathology.

[21]  J. Bradfield Neoplasms of the Larynx , 1994 .

[22]  R. Hybels,et al.  The pathology of head and neck tumors: verrucous carcinoma, Part 15. , 1982, Head & neck surgery.

[23]  Ober Wb The case of the Kaiser's cancer. , 1970 .

[24]  L. Goldberg,et al.  VERRUCOUS CARCINOMA OF THE ORAL CAVITY , 1994, International journal of dermatology.

[25]  M. Mackenzie Essay on growths in the larynx : with reports, and an analysis of one hundred consecutive cases treated by the author, and a tabular statement of all published cases treated by other practitioners since the invention of the laryngoscope , 1871 .

[26]  P. Imhof,et al.  Excretion of Urinary Casts after the Administration of Diuretics , 1972, British medical journal.

[27]  J. Olofsson,et al.  Verrucous carcinoma of the larynx. A clinical and pathologic study of 10 cases , 1972, Cancer.

[28]  Thomas F. Smith,et al.  Polymerase chain reaction (PCR) identification of human papillomavirus (HPV) DNA in verrucous carcinoma of the larynx , 1993, The Laryngoscope.

[29]  K. Olsen,et al.  Verrucous carcinoma of the larynx: A review of 53 patients , 1998, Head and Neck.

[30]  M. Dietel,et al.  Pathologisch-Anatomisches Cabinet : vom Virchow-Museum zum Berliner Medizinhistorischen Museum in der Charité , 1996 .

[31]  A. Ferlito,et al.  Ackerman's tumor (verrucous carcinoma) of the larynx. A clinicopathologic study of 77 cases , 1980, Cancer.

[32]  N. Gale,et al.  Pathology of the Head and Neck , 2010 .

[33]  R. Virchow,et al.  Die Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebelehre , 1861 .

[34]  S. Mills,et al.  Verruca vulgaris of the larynx: A distinctive lesion of probable viral origin confused with verrucous carcinoma , 1982, The American journal of surgical pathology.

[35]  K. Shanmugaratnam Histological Typing of Tumours of the Upper Respiratory Tract and Ear , 1991, World Health Organization.