A retrospective study on the clinical features of skin lesions in Chinese acquired digital fibrokeratoma patients

Acquired digital fibrokeratoma (ADFK) is an uncommon benign fibro‐epithelioma, which is rarely reported in China.


| INTRODUC TI ON
Acquired digital fibrokeratoma (ADFK) is a rare benign fibroepithelioma, typically adjacent to the phalangeal joints of fingers and toes, which was first reported and named by Bart in 1968. 1 Typical clinical features of ADFK are branching, dome-shaped, rod-shaped, or flattened hyperplasia emerged directly from the proximal nail fold or nail bed, leading to overgrowth of the nail plate or direct damage to the nail matrix, with concomitant deformities: longitudinal groove and trachyonychia. 2 Due to slow tumor growth, there is often no subjective symptom.Since most previous literatures only reported individual cases [3][4][5] and the clinical features were rarely summarized, lack of systematic analysis of ADFK in Chinese people up to now, so we collected 21 ADFK cases in Chinese people, analyzed their clinical and pathological manifestations, and observed the therapeutic outcome as well as the follow-up conditions.

| ME THODS
The 21 ADFK cases are patients undergoing outpatient surgery at the dermatology department of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2019 to June 2021.This study was approved by the institutional review board of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and informed consent was obtained from all study subjects.We analyzed medical history, clinical pictures, and medical records of the patients (including gender, age, course of disease, site, clinical morphology, treatment methods, follow-up visits, history of trauma, and previous treatments).Those with syndromes or systemic diseases such as tuberous sclerosis associated with ADFK were excluded.ADFKs were classified into three morphological types: rod-shaped, dome-shaped, and branching (Figure 1), and three sites: periungual area, nail bed, and intraungual area (proximal nail fold and nail matrix; Figure 2).All ADFK patients were diagnosed based on pathology results and have done complete surgical excision.

| Surgical procedure
Periungual area: A spindle incision was made at the base of the ADFK extending to the fat layer; the tumor was amputated at the adipose layer; and the skin was sutured.
Nail bed: When the nail plate was removed, the base was seen connected with the nail bed.Spindle-shaped excision was performed to the base, extending to the surface of the phalange.Full layer of the nail bed tissue was dissociated bilaterally, and the wound was dealt with apposition suture.
Intraungual area (Figure 3): Two oblique incisions were made at the proximal nail fold, which was reflexed.Half of the proximal nail plate was opened to clearly expose the root of the tumor body.Two longitudinal incisions extending to the surface of the phalange were made bilaterally; the tumor was completely resected; and the nail matrix was sutured.

| General characteristics of the patients
As is shown from the Tables 1 and 2, all patients are adults with a wide age range from 25 to 78 (44.48 ± 15.95) years old, without family history, presenting as single skin lesion.The ratio of ADFK in males to females was 9:12, and the ratio of ADFK on toenails to fingernails was 11:10.There were five patients with skin lesion on the hand having a history of local trauma/infection before onset, while etiology in the other five patients was unknown.There were two patients whose ADFK occurred on the foot reporting a history of trauma before onset, and trauma and infection are mostly caused by reverse stripping.

| Clinical features of ADFK in Chinese patients
In females, it occurred typically on the fingernails (7/10, 70%), while it occurred typically on the toenails (6/11, 54.5%) in males.The ratio of occurrence on the left hand to the right hand is 4:6, and the ratio of occurrence on the left foot to the right foot is 2:9.Regarding of the fingernails, the lesion site much more happens on the middle finger (6/10, 60%), followed by two patients on the thumb and forefinger, respectively, while other fingers were not damaged in these cases.For toenails, it was more likely to occur on the great toe (5/11, 45.5%), followed by two patients on the second toe and fifth toe, respectively, and one patient on the third toe and fourth toe, respectively.

| Pathological features of ADFK
Generally speaking, the lesions presented as disc-shaped with a relatively wider base or rod-shaped.Under microscope, all cases manifested as epidermal hyperkeratosis which may be associated with acanthosis, broadened trochanterellus whose component was branching (Figure 5A-D), as well as intradermal fibroblast proliferation which may be associated with dense fibroplasia (Figure 5B).
When there was significant collagenous degeneration, it could be scarry (Figure 5C), some superficial collagenous fibers of the dermis were perpendicular to the epidermis.Microvascular proliferation was visible.Nevertheless, dilation of small vessels was observed in individual patients, presenting as angioderatoma-like image (Figure 5D).
Besides, a few inflammatory cells presented in some patients.

| Postoperative follow-up
All the patients underwent surgical resection and were followed up   Acquired digital fibrokeratoma (ADFK) is a benign acquired fibrous and collagen proliferative tumor, which may occur on the digits and palmoplantar area, 3,6,7 typically measuring <1 cm in diameter and asymptomatic.There are a few cases reporting skin lesions measuring >1 cm in diameter, associated with marked pain. 8Under dermoscope, ADFK is typically manifested as a central homogeneous light-yellow skin lesion, with white collar-shape surrounded keratin scales peripherally, regular light white cracks on the surface, some of which may present as punctate blood vessels.
Etiology of ADFK is unknown till now.In our study, there are 33.3%patients having a history of trauma or infection, which is higher (50%) in those patients whose ADFK occurred on the hands.This finding was similar with previous literatures as well, which believed that the occurrence of ADFK is related to trauma, repeat stimulation, 9,10 infection or other external factors. 11,12However, some patients did not had a definitive history of trauma. 13We believe that the patients may be unconscious of the microlesions caused by friction of the lesion site, leading to lack of clinical evidence of a trauma history.This may be the reason why the ratio of our patients whose ADFK occurred on the hands with a definite history of trauma/infection is higher.Besides, some investigators believe that ADFK is resulted from the growth of new collagen tissues in the fibroblasts, as fibrous tissues in the tumor body are denser than that in the normal dermis, containing more capillaries and fibroblasts as well as thicker elastic fibers. 7It is proved that ADFK is a product secondary to traumatic stimulation, which is consistent with our point of view.
The diagnosis of ADFK is mainly base on pathology.Meanwhile, ADFK should be differentiated from several other conditions (Table 3): (1) Cellular digital fibroma shows a prominent cellular proliferation of spindle-shaped fibroblasts, without any atypia or mitoses, that extends from the papillary into the upper reticular dermis.CD34 staining is diffuse and strongly positive present throughout the entire tumor. 14,15(2) Cutaneous horn: typically appears as a cone-shaped or cylindrical keratoplastic injury, rough in surface and hard.Histopathological feature is marked excessively keratosic epidermis, whose base tissue imaging depends on the primary lesion, which is sometimes benign epidermal proliferation, and sometimes malignant.However, though skin lesion of the patient in our study presented as rod-shaped, it reveals a relatively smooth surface, and histopathological changes suggest relatively homogeneous hyperkeratosis throughout the epidermis. 16(3) Dermatofibroma: a firm nodule adhered to the surface skin, histopathological feature of which is marked downward proliferation of the trochanterellus, and proliferative and alternately arranged intradermal fibroblasts and collagen. 3(4) Periungual and subungual fibroma: a sin finding of tuberous sclerosis, whose pathology is similar to that of ADFK, but clinically different.Periungual fibroma is typical in adolescents, which may present as multiple, asymptomatic, skin-colored or faint red oval or filamentous damage, associated with steatadenoma and shagreen patches, which is easy to recur. 17  It is also typical on the digital, with a history of trauma before onset, which is typically a fast-growing exogenous red nodule, soft, with an erosive surface, whose pathological results suggest clustered intradermal microvascular proliferation, with bilateral epidermis presenting as collar-shaped downward extension.It is proposed by all the previous reviews that ADFK is a rare tumor.However, we find during case collection that ADFK is not uncommon, which typically occurs to adults ≥40 years old (15/21).After analysis, we find that morbidity of the right hand and right foot is higher than that of the left, which may be related to getting used to movement with right limbs, pressure, and susceptible to injury.In females, ADFK is typically on the fingernails, which is up to 71.4%, which may be related to long-term housework, nail beauty, and other mechanical forces.
In males, ADFK is typically on the toenails, which may be related to recurrence can be assured.During the operation, tourniquet should be released at regular intervals, so as to avoid tissue ischemia.After excision of the mass, there will be a tissue space inferior to the nail wall.Therefore, after adequate hemostasis, appropriate compression bandaging is essential.In our study, all the 14 patients whose ADFK occurred on the nail wall got surgery following the aforesaid principle, and all of them are satisfied with the therapeutic outcome.
Nonetheless, our study also has some insufficiencies.For example, etiology of some patients cannot be traced in detail due to long disease course, it is a retrospective study, sample size is limited, and pathogenesis and mechanism of ADFK still need to be further investigated.

AUTH O R CO NTR I B UTI O N S
Yang Liu, Yueqian Zhu, Yamin Rao, Ke Liu concept, manuscript writing, editing and review.Guodong Chen, Hui Xu data collection and analysis, manuscript preparation.All authors have read and approve the submission of the manuscript.

for 6 -
17 months.None of the patients relapsed.All of them are satisfied with the postoperative efficacy, whose longitudinal groove and trachyonychia are recovered.

F I G U R E 1
Shows rod shape (A), dome shape (B), and wart shape (C).F I G U R E 2 Shows periungual area (A), nail bed (B), proximal nail fold (C), and nail matrix (D).

F I G U R E 3
Shows the surgical process of intraungual acquired digital fibrokeratoma (ADFK).(A) An ADFK of the second toe.(B) Exposing the tumor after stripping the proximal nail fold from the nail plate.(C) Suturing the two oblique incisions after ADFK excision.

( 5 )
Pyogenic granuloma: TA B L E 1 General information of the patients.

F I G U R E 5
doing exercise and shoe wearing habit.Typical rod-shaped ADFK on the toenails may be related to excessive squeezing to the foot.Typical histopathological changes of ADFK are featured by hyperkeratosis, acanthosis, focal thickening of the granular layer, and irregular downward extension of the epidermal horn.Center of the tumor is composed of incrassated eosinophilic collagen which are intertwined with each other, arranged mainly consistent with the long axis of the tumor, with rare inflammatory cell invasion.Skin appendages is visible in dermis. 4All 21 patients are consistent with the above features.Moreover, it can be classified into three subtypes according to different collagen fiber morphology arrangements in the tumor center: Most Type 1 ADFKs are dome shaped, whose TA B L E 2 Location of acquired digital fibrokeratomas.U R E 4 (A) Clinical morphology of acquired digital fibrokeratoma (ADFK); (B) Location of ADFK.Shows hyperkeratosis in all patients, presenting as domeshaped (A), interstitial fibrous tissue proliferation, different from the normal connective tissue beneath (B).Besides, it also presents as rod-shaped, dense fibrous tissue proliferation (C), with varied vascular proliferation amount, which may present as angiomatoid image (D).(Bar = 1 mm).collagen bundles of dermis are proliferative, dense and irregularly arranged or parallel to the long axis of the tumor.Fibroblasts are visible among the collagen bundles.Structure of the lesion is different from the normal connective tissue beneath, and there are a lot of capillaries in the mesenchyme.Type 2 ADFKs are rod-shaped with hyperkeratosis, and densely proliferative dermis collagen arranged in parallel on the long axis of the lesion.Fibroblasts are markedly proliferative, which can present as bunchy proliferation but similar with the inferior connective tissue.Type 3 ADFKs are largely flat or dome-shaped, with relatively fewer edematous dermal mesenchymal cells, as well as irregularly arranged fine collagen bundles.Both Type 1 and Type 2 ADFKs are more common, while Type 3 ADFKs are rare.In our study, there are 8 Type 1 cases and 13 Type 2 cases consistent with this conclusion.In terms of treatment, it is worth noting that partial excision or curettage is easy to cause recurrence. 4ADFK typically affects the nail wall, and in our study, there are 14 cases whose ADFK occurred on the nail wall.When ADFK occurs on the nail wall, it is difficult to do the surgery as the nail plate between the tumor proximal base and the nail matrix proximity is very thin or absent.Forcible separation will damage the nail matrix, leading to deformation or excalation of the nail, resulting in aesthetic concerns.Therefore, opening the two included angles at the junction of the proximal nail fold and lateral nail fold during the surgical operation is beneficial for upturning the proximal nail wall.If the tumor body is too thin in diameter or adjacent to the lateral nail wall, just open nail wall of one side or part lateral nail wall to fully expose the tumor body or peripheral tissues.Otherwise, open nail wall of the other side as well.Only when adequately and completely excised from the base where the tumor is attached, no