Clinical Reference / Dermatopathology: Practical & Conceptual / Jul – Sep 2000 | Vol. 6, No. 3 / Walter Freudenthal: An eleucidator of solar keratosis lost in time

Walter Freudenthal: An eleucidator of solar keratosis lost in time

Jul – Sep 2000 | Vol. 6, No. 3
Kiehlmann, Ingomar

Introduction

“The Senate minutes occasionally record obituaries but I have been unable to find an entry for Walter Freudenthal.” – Judith Etherton, University Archivist at the University of London Library, 1999.

Among Walter Freudenthal’s numerous works, the most memorable is the one titled “Verruca senilis und Keratoma senile” published in the Archiv für Dermatologie und Syphilis in 1926. In that article, Freudenthal characterized, for the first time, Keratoma senile (solar keratosis, actinic keratosis) histopathologically and distinguished it from Verruca senilis (seborrheic keratosis). Many of the criteria for diagnosis set forth by him are still employed today. What follows is a translation of excerpts from Freudenthal’s seminal publication about solar keratosis (Keratoma senile).

Freudenthal: The Findings

“My histological material of typical Keratoma senile derives from 14 biopsy specimens taken from six men and seven women between the ages of 34 and 76 years. Two lesions were situated on the back of the hand; all of the others were on the upper part of the face.

Now that I have completed all my own examinations, I believe I can speak about Keratoma senile without great detail and describe it in general. It is important to note before going into any detail that when viewed histopathologically, Keratoma senile has a unique and characteristic silhouette. The usual findings of Keratoma senile are not always observed in each lesion and some of the characteristics of Keratoma senile may be found in other lesions. The overview of the entire lesion, however, is so typical of keratoma senile that nearly no mistake can be made in diagnosis of it.

In the epidermis there is inter- and intracellular (especially paranuclear) edema of the cells of the basal layer. The edema is one of the earliest changes encountered. In many examples, the severity of the edema may reach the point where a cleft may actually be seen above the basal layer (his Figures 5 and 10; our Figures 1 and 6).

The aforementioned blister-like clefts are usually empty. However, in these clefts spine-like structures sometimes can be found. Single round cells and disconnected epithelial cells may be encountered at times. Surrounding the blisters, the spinous cells are disconnected consequent to the effects of intercellular edema, but the spines themselves remain intact. The basal layer is the starting point for the growth of the atypical epithelium (his Figures 6, 9, and 10; our Figures 2, 5, and 6) which may be small or large, but in both cases the growth will end up bigger than it began. The growth of epithelium also can be straight or oblique, and as the numbers of epithelial cells increase, buds and pegs of them grow into the papillary dermis . . .

The number of mitoses in the growth of epithelium is increased, especially in the surrounding clumped cells and giant cells. It is there where most of the atypical mitotic figures can be found. In the stratum spinosum, besides the already described changes [clumped cells and giant cells], there is a little inter- and intracellular edema. These cells are generally wider and are stained pale, which can be seen readily in the Pappenheim stain (his Figures 7 and 8; our Figures 3 and 4) . . . The stratum granulosum beneath the epidermis [below the parakeratotic cornified layer] usually is missing, but is thicker above the masses of horn devoid of nuclei. The cornified layer is often extremely thick. As you look at Keratoma senile you often can see nuclei in the cornified layer, but never in the cornified layer above the follicle and the openings of the sweat ducts. (his Figures 5, 6, 8, 9; our Figures 1, 2, 4, 5). Parenthetically, the orthohyperkeratotic columns are often shorter than the parakeratotic ones.

Fig. 1

Keratoma senile. Tall columns of parakeratosis. Above the opening of the follicle the keratinocytes have no nuclei (cut slightly obliquely). Clefts have formed above the epidermal basal layer. A mantle of cells surrounds the follicle. Dense round-cell infiltration. (His Figure 5)

Fig. 2

Keratoma senile. Tall parakeratotic columns. Alternation with shorter masses of horn devoid of nuclei which go into the openings of the follicle and the ducts of sweat glands. This section is cut slightly obliquely. Epidermis: In part, broad irregular acanthosis and, in foci, cones and buds. Masses of clumped cells and giant cells. (His Figure 6)

Fig. 3

Keratoma senile. Tall parakeratotic columns. Alternation with shorter masses of horn devoid of nuclei which go into the openings of the follicle and the ducts of sweat glands. This section is cut slightly obliquely. Epidermis: In part, broad irregular acanthosis and, in foci, cones and buds. Masses of clumped cells and giant cells. (His Figure 6)

Fig. 4

Keratoma senile. (Unna-Pappenheim-stain.) Parakeratotic cornified layer; spheres, which look triangular in this section, always enter the opening of the follicles and the sweat ducts. These spheres never contain nuclei. They are stained dark red and are separated from the pale column of epithelial cells. (His Figure 8)

Fig. 5

Keratoma senile. (Unna-Pappenheim-stain.) The darkly stained parakeratotic layer lies above a pale epidermis. The parakeratotic layer is sharply circumscribed from the dark red masses of horn that lie within the epidermis. The masses of horn contain no nuclei. Also a little acanthosis may be seen in company with buds and formations shaped like cones. The infiltration of round cells is uneven in distribution. (His Figure 9)

Fig. 6

Keratoma senile. Darier-like atypia. Hyper- and parakeratotic columns of horn. Atypical growth of epithelium in the form of cones and buds. Development of clefts. Grains and corps ronds. This is shown at a higher magnification. (His Figure 10)

The slightly elevated epidermis usually is a little thicker. In the papillary dermis there are dense infiltrates of round cells. The vessels surrounding the elevated epidermis also are wider. The amount of the infiltration does not always correspond to the extent of growth of atypical epithelium. Round cells rarely are seen in the epidermis.

Referring to Figure 8 (our Figure 4), the changes that occur in the dermis appear to be related to age. I could not find other changes that correspond to external factors, such as gender, height, etc.

We will now try to summarize all the histopathologic changes that occur in a Keratoma senile: The cornified layer is greatly thickened, and there is a change between parakeratotic columns and orthohyperkeratotic masses, the latter entering the opening of the follicles and the sweat ducts.

Growth of atypical epithelium goes into the papillary dermis in the form of buds and cones. Clefts may be seen often above the basal layer or above the growth of epithelium.

The infiltration in the papillary dermis consists of round cells, which sometimes appear along the border between the epidermis and the dermis, and sometimes in perivascular location.

The most important thing, as I stated previously, is the specificity of the histopathologic appearance of Keratoma senile. It is possible that Keratoma senile is caused by sunlight. However, there is no certainty of this.

It is my belief that over the course of a lifetime, the skin gains an ability to react to sunlight, thereby preventing the rays from causing further disease.

It is my belief, too, that the difference in parakeratosis between the cornified layer of interadnexal skin and the cornified layer above the follicles and the sweat ducts [of Keratoma senile] is due to the fact that the basal layer in the latter is situated deeper. Therefore, no abnormal change occurs in the skin above the follicles and sweat ducts. This, however, does not appear adequate to explain fully the changes in the skin.

In my opinion, the clefts and the blister-like spaces are not artificial, but rather exist in vivo. These clefts and blister-like spaces are filled with a liquid that contains very few proteins. When a section is affixed to a slide, the liquid within the cleft is squeezed out, and all that is left is the clefts. During a review of several of these cases, I have seen cells within the intraepidermal clefts that appear to be disconnected and overly large. I do not believe that this is Darier’s disease. These changes simply appear to be a Darier-like change of Keratoma senile.

I would have liked to show the slow transition between Keratoma senile and cancer. When doing excisions, however, I could not find this situation exactly. I was able to find either an individual Keratoma senile or, more often, a fully developed cancer. When looking at the cancer, I was unable to see any remnants of Keratoma senile. Eventually, however, I was able to find a transition between Keratoma senile and cancer . . .

Conclusion

Keratoma senile is a distinct lesion unlike any other, with its own characteristic and specific histopathologic picture. That is the reason why you must consider Keratoma senile to be a lesion unto itself.”

With the publication of “Verruca senilis and Keratoma senile,” Freudenthal elucidated for the first time the histopathologic attributes of solar keratosis and implied that it was, in actuality, a type of superficial squamous-cell carcinoma. As an aside, it is worth mentioning that he also was the first to describe suprabasal clefts that occur so often in solar keratosis. That Darier-like change is the equivalent of pseudoglandular squamous-cell carcinoma.

Freudenthal: The Man

Walter Freudenthal (Fig. 7) was born on May 6th, 1893 in Breslau in the Silesia district of Germany (today Wroclaw, Poland) into a Jewish family of doctors. He began his medical training in Geneva, Switzerland in 1913. In 1919 he returned to Breslau to continue his studies at the Clinic of the Friedrich-Wilhelms University, from which he graduated in 1920. During his time, as head of the men’s ward in the outpatient clinic and while working in the histopathologic laboratory, he completed his qualification for university lecturer and later was elevated to full professor. He presented lectures about dermatology, dermatohistology, dermatohistopathology, therapy of skin diseases, and sexual transmitted diseases. At that time, Freudenthal also worked for a pharmacist in order to learn about the ingredients of ointments and creams, the reason being that he thought that all existing formulae for diseases of the skin were unsatisfactory as modes of therapy.

Fig. 7

W. Freudenthal

The takeover of Germany by the Nazis in 1933 ended the creative period for dermatology in Breslau and for Freudenthal. Many of the doctors at the clinic were Jewish or of Jewish origin. The Third Reich issued a decree to the effect that “The minister of the Reich can withdraw from a lecturer the authorization to teach, if it is in the interest of the university.” This order, which left much room for interpretation, subsequently was used by the Nazis to prohibit teaching by all Jewish instructors, including Freudenthal.

In 1933, Walter Freudenthal was one of the first Jews to leave Nazi Germany for England, a courageous and farsighted decision. There Sir Archibald Gray made it possible for him to continue his studies of histopathologic findings in the skin at the main University College Hospital in London. As a German Jew, in consideration of his host country, he deliberately refrained from obtaining the English certification in medicine and thus gave up the practice of clinical dermatology in order not to compete with English dermatologists who already were established in practice. Instead he dedicated himself to science.

Freudenthal was later appointed to the teaching faculty, as a dermatohistopathologist, at the University College Hospital in London. As a pioneer, he was elected in 1945 to the first readership ever in Dermatological Histology and functioned in this capacity for the rest of his professional life. Within the field of histopathology he performed admirably by making noteworthy comments at meetings of the section of dermatology of the Royal Society of Medicine, by advising domestic and foreign dermatologists about matters dermatopathologic, and by giving demonstrations and lectures. After a five-year battle with cardiac disease, Walter Freudenthal, died at age 58 in London on May 27th, 1952. That same morning he had worked, as usual, in his laboratory. According to English colleagues, Freudenthal’s influence on English dermatology was a lasting one.

During his time as a physician in Breslau, the creative atmosphere of the University clinic inspired Freudenthal, as it did many others. It was in this environment of the University Clinic of Breslau that Freudenthal wrote most of his remarkable articles. His main efforts were focused on issues in dermatopathology. According to W.N. Goldsmith, a colleague from Breslau, Freudenthal was regarded as “a talented and obliging person with varied interests.” The department at the University of Breslau was a center for dermatologists from all over the world, and its atmosphere was animated mainly by creative thinkers and avid practitioners of dermatology, men like Joseph Jadassohn, Max Jessner, and Rudolf Mayer. Professor Jadassohn, chairman of Dermatology in Breslau from 1917 to 1931, was a quiet and circumspect man who refused to participate in political games at the University (he even had rejected an offer of chairmanship in Berlin). He was Freudenthal’s most important teacher and had a notable impact on him.

Goldsmith described Freudenthal posthumously as follows: “He was a reserved character, often taciturn but not always revealing to people and he was very much an individual. The one quality of Freudenthal that was most impressive was the genuineness of his nature.” Ruth Hoffmann, a poet and friend of Freudenthal, dedicated nearly an entire chapter to him in her book, “Meine Freunde aus Davids Geschlecht (My friends from David’s lineage),” that was published in 1947 in Berlin. She described Freudenthal’s character in these words: “Being in his company permitted a sense for capability and zest for life. The man was sitting at the riverbank of life, using a net like a fisherman, especially on artists. If a rare fish, like the painter Steffke, swam into his net, Freudenthal would be delighted. His artistic interest was accompanied by a tremendous love for Mother Nature.” Ruth Hoffmann wrote delightful anecdotes about Freudenthal’s excursions with friends, despite inclement weather, in lines like these: “We walked with him and he showed us the tempting landscape and verily he was an artist of discovery, reconnaissance, and pleasure. Into the sun he went with us, everything he touched became a success – work, friendship, and confidence. When dark clouds appeared on the horizon, creativity was buried alive with no mercy. He waved his handkerchief and the magic sleigh whisked him away to where he is, a remarkable scientist, physician, worker, and man in perpetuity.” Hoffmann captured the appearance and person of Freudenthal thus: “A man with thinning, blackish hair, an unmistakable, nimble, bird-like gait, who would disappear as fast as he had approached. He would depart with a short farewell, which would not last longer than the usual good-bye on the main station of Breslau after a weekend trip, even when it involved foreign travel, the ocean, years, and war.”

It happens from time to time that an original idea and the one who spawned it are deemed insignificant and forgotten, lost and never recovered. Sometimes, however, a work may be rediscovered and recognized as containing genius. The observations of Walter Freudenthal about Keratoma senile in 1926 were disregarded for almost 75 years. This article seeks to contribute to the revivification of the life and work of Freudenthal, a mostly forgotten German Jew who was one of the leading dermatologists and dermatopathologists of his time. Perhaps this story may sensitize each reader of it to the fact that the fate of individuals and the knowledge generated by them may be buried in the vault of libraries and our responsibility is to unearth them.

Acknowledgement

David Muraskin, prior to entering 10th grade at Germantown Friends School, spent several weeks at the Ackerman Academy during the summer of 1999, and assisted in this project.

Dr. Kiehlmann did this work while a Visiting Fellow at the Ackerman Academy in New York City. He is now at Hautklinik in Norderney, Germany.

References

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