Uomo di 50 anni, da pochi mesi comparsa di lesioni micro papulose diffuse al collo (fig.1).

FIG  2	FIG  3

Le lesioni, che si osservano anche sulla nuca (fig.2) e tronco (fig.3),

FIG  4

conferiscono alla cute un aspetto a “ buccia di arancia” (fig.4).

L’esame istologico mostra una diffusa infiltrazione interstiziale del derma da parte di elementi fibroblastoidi, alcuni dei quali a morfologia “stellata”, con ipercromasia nucleare e atipie citologiche.

FIG 5

Si associano densa fibroplasia dermica e diffusi depositi di mucina (fig.5) positivi con la colorazione di Alcian a pH 2.5.

Le indagini ematochimiche e strumentali non hanno evidenziato alcuna alterazione, in particolare non si è riscontrata paraproteinemia.

Il paziente trattato con talidomide e immunoglobuline ha mostrato un netto miglioramento delle lesioni.

COMMENTO

Lo scleromixedema (variante generalizzata della mucinosi papulosa o lichen mixedematoso) è una rara affezione che colpisce tipicamente gli adulti di media età senza predilezione di sesso.

E’ caratterizzata da una eruzione simmetrica e diffusa di papule traslucide di pochi mm. di diametro, confluenti in ampie placche, spesso a distribuzione lineare, che conferiscono alla cute un aspetto reminiscente la sclerodermia. Le sedi più frequentemente coinvolte sono il dorso delle mani, gli avambracci, il volto, il collo, la parte superiore del tronco e le cosce. Si associano talora eritema, edema ed iperpigmentazione brunastra; le mucose sono risparmiate. Nelle fasi avanzate compaiono sclerodattilia e disturbi articolari.

Tale patologia è correlata a diversi disturbi sistemici e quasi costantemente a paraproteinemia, generalmente di tipo IgG lambda, con evoluzione in mieloma multiplo nel 10% dei casi. Sono descritte altre associazioni con linfomi di Hodgkin e non Hodgkin, macroglobulinemia di Waldenstrom e leucemie.

Bibliografia:
Rongioletti F, Rebora A. Updated classification of papular mucinosis, lichen myxedematosus, and scleromyxedema. J Am Acad Dermatol 2001;44:273-81.

Cordialmente,

Raffaele Gianotti
Dermatopatologo
Istituto di Scienze Dermatologiche, Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
Milano

Dear Colleagues,

HOW IS FUNGUS SEARCHED IN THE FOOT?

Most of the search for fungi takes place by means of scrapings of volar horn treated with KOH for softening and clearing, followed by microscopic observation of coverslipped slides, either unstained or stained with ink or similar dyes.

Occurring several times a day in a dermatologic office, besides time-consuming, KOH preparation could also interrupt the flow of the examination of the now busy medical practices of modern times.

IS THERE ANOTHER WAY TO DO IT?

A better way of fungus search is the use of the VOLAR CORNEAL BIOPSY (VCB), i.e., the use of the cornified scrapings or clippings from the foot (or hand) for histologic examination, instead of a KOH preparation.

In my area of the United States (Metropolitan Boston), more clinicians, particularly podiatrists, are often using this method that has arisen parallel to the use of the nail plate biopsy, already described in these letters.

There is an advantage to this referral that does not come readily to the front of the argument and it is simply the convenience of delegation of the duty into the pathologist in search for greater accuracy in the diagnosis of tinea pedis using the more stable and better stained sections prepared histologically from the harvested horn.

WHY YOU SHOULD TRY IT?

Granting the advantage that immediate result for the KOH in the office speeds the therapy for positive cases, the risk of false negatives increases as well. The benefit of the greater sensitivity of the VCB surpasses any perceived disadvantage.

Although KOH is a time-honored technique, it pays to concentrate in newer techniques in other areas of the dermatologic practice that may be more beneficial to both patients and doctors than practicing the traditional routine of a KOH exam. As in onychomycosis, the results of PAS-stained tissue sections are better than direct examination.

HOW IS IT DONE?

Simply, in fact: after the scraping is done, formalin fixation is unnecessary. Bagging the fresh specimen and sending it to the laboratory, even mailing it, suffices.

With relatively clean sample-taking, not even in aseptic conditions, a belated fungal culture from fresh portions of the specimen could be performed several days after the specimen has been received by the laboratory. This step can be done in nails that at first are PAS-negative to see if the culture achieves a “rescue” and a diagnosis of tinea pedis can still be made, in spite of cultures being less sensitive than PAS stain to detect fungi, at least in nail clippings.

NOW LET’S TALK ABOUT RESULTS…

The soundness of initial air-dry fixation to keep intact the histologic features of horns and even epithelia is assured. There is practically no decay in the histology of squamous epithelia, from epidermis to matrical or lectural epithelium.

Formalin fixation of the samples after arrival to the lab is more than sufficient to insure adequate processing. This “nonviable” tissue ‑the horn from a foot‑ is so full of information when it is processed as a biopsy that one wonders that the volar corneal biopsy has not been used more often or in earlier medical practice. Besides containing no epidermis or only a little (according to the vigor applied to the curettage or scraping), the histologic sections are in equal terms to those of deeper viable tissues derived from the punch or shave technique.

The tissue is embedded is sectioned and stained with both hematoxylin and eosin and, more importantly, PAS stain (one without diastase digestion is sufficient). A Gomori Methenamine Silver (or Grocott stain) can be complementary but it is generally unnecessary.

Fig. 1, Volar Horn, Tinea Pedis, GMS Stain

The morphology of the fungi will allow, like in nail plate biopsies, the suggestion of class, genus and even species based on the morphologic characteristics of the isolate.

WHAT OTHER MICROBES CAN BE PICKED UP?

Fig. 2, Subungual Horn, Filamentous Corynebacteria, PAS Stain

Not only fungi can be identified. It is not uncommon that Corynebacterium minutissimum, the agent of the underestimated pitted keratolysis of the soles, can be detected. The defining thin granules and filaments making the diphtheroid will stand up in the PAS stain. There is no need to perform a Brown-Brenn (Gram) stain but one could follow for confirmation of the Gram-positive character of the bacterium.

WHAT OTHER DISEASES CAN BE DIAGNOSED?

Fig. 3, Volar Horn, Dyshidrotic Dermatitis, PAS Stain

Even after all stains are negative for organisms, there is the added certainty that a pseudomycotic horn may be that of dyshidrotic dermatitis or, even, psoriasis.

Fig. 4, Volar Horn, Probable Psoriasis, PAS Stain

This is an additional bonus to the examination:

the negative horn of eczematous dermatitis could be as useful to management of a patient as is the assertion of the presence of tinea pedis.

TAKE-HOME MESSAGE

The transformation of a KOH examination into a minibiopsy of corneal elements of the skin is another nonexfoliative cytologic procedure that is processed as if it was an invasive biopsy of the skin. Cytology and histology meet at the foot!

This underutilized volar corneal biopsy may increase the range of the diagnosis of tinea pedis and may ultimately help in the prevention of tinea unguium associated with and probably following a longstanding case of tinea pedis.

FROM A DERMATOPATHOLOGIST TO YOU!

Finally there goes a desideratum. The above arguments go to stimulate the use of a dermatopathologist in the resolution of some aspects of the dermatologic practice other than the traditional tissue biopsy. Strengthening the binomial partnership of dermatologists and pathologists may be very rewarding to the success of each other’s practice.

Cordiali saluti,

Aldo González-Serva, MD

IS THERE A SAVING GRACE TO SHALLOW SHAVE BIOPSIES?
Fortunately, the horn of diverse conditions will frequently reflect the nature of the epidermis or other deeper foot structures that have induced the thickening of the cornified layer. Thus, even in the absence of viable tissues, the pathologist may be able to surmise the diagnosis on the basis of the horn. While this is an indirect approach that is not fool-proof, it will be enough on most occasions to help the clinician decide what to do next.

WHICH IS THE FIRST TELLTALE SIGN THAT SAVE THE SHALLOW BIOPSY?
At the least, the milieu that surrounds the volar horn without viable tissues will tell if a malignancy lurks nearby. In clinically benign conditions, a good “horn milieu” will reinforce the diagnosis of benignancy and may even temper the need for a repeat biopsy, at least for a prudential lapse. A good milieu is horn without evidence of necrotic debris or blood cells and showing only limited parakeratosis and relative homogeneity of its structure. It will be seen in most warts, corns or other benign keratodermas. A bad milieu, in contrast, will show horn that is heterogeneous, degenerated, massively parakeratotic, probably impetiginized and often associated with necrotic debris. All these signs reflect serious abnormalities of the underlying tissues, even if they do not appear under the microscope.

HOW IS THE HORN OF BENIGN LESIONS?
The most common diagnostic horn will be that of the plantar verruca, whose cornified layer will be thickened. This trait is more easily discerned if normal horn is also present. The abnormal warty horn will be orthokeratotic (devoid of nuclear residues) or, most commonly, parakeratotic (bearing residues of the nuclei of generating keratinocytes). The parakeratosis will be uniform, practically symmetric, without dramatic changes in its composition and lacking the accoutrements of a bad milieu.

The callus (hypertrophic lichen simplex chronicus), being a response to persistent blunt rubbing, will display a thickened horn that is almost without exception orthokeratotic. It will be basophilic, as is normal in volar skin biopsies stained with hematoxylin and eosin stain.

The heloma durum (corn) will contain a broad column of parakeratosis as if it were a cylindrical clavus buried among more normal horn or stuck in horn resembling that of a callus.

WHAT HAPPEN TO THE HORN ABOVE MALIGNANT CONDITIONS?
In malignant conditions, two important entities dramatically modify the horn. One is verrucous carcinoma (epithelioma cuniculatum); the other is malignant melanoma.

Verrucous carcinoma is generally exophytic and hyperkeratotic. That excessive horn is markedly abnormal. Besides being irregularly parakeratotic, the nuclear ghostly contours are dissimilar, often laid in the bowl-shaped streams that reflect the recesses and sinuses that characterize verrucous carcinomas.

Melanoma, although not generally a hyperkeratotic disorder, is one with marked abnormalities of the pigmentary system. This hyperpigmentation (absent, though, in amelanotic melanoma) will bleach into the horn. Coarse dark-brown melanin granules will permeate the corneocytes irregularly and asymmetrically, mirroring the abnormal growth of the melanoma in the undisclosed epidermis.

A SUMMATION
Not everything is lost when an acral shave biopsy misses the deeper tissues. The superficial horn will often tell the tale! Everyone should keep in mind the importance of using this ‘shallow’ information in most benign cases or in inducing a new biopsy in suspicious cases in the near future.

©Aldo González-Serva, MD
Dermatopathologist
Boston, MA, USA

Fig 1

Donna di 55 anni, presenta da circa due anni alla nuca lesioni papulo-nodulari eritematose, asintomatiche, in lento accrescimento. Alcuni elementi tendono a confluire in placche (Fig. 1,2). L’esame istologico mostra una proliferazione di vasi con cellule endoteliali di aspetto epitelioideo o istiocitoide, con tendenza alla protrusione endoluminale (Fig. 3,4,5). Si associa un denso infiltrato linfocitario perivasale ricco di eosinofili.

Fig. 2	Fig. 3
Fig. 4	Fig. 5
Fig5

Commento

L’iperplasia angiolinfoide con eosinofilia è una proliferazione vascolare di probabile natura reattiva, caratterizzata dalla comparsa di lesioni papulo-nodulari multiple più frequentemente al capo e, in particolare, al condotto uditivo esterno. Tale entità è raramente associata a linfoadenopatia regionale e solo nel 20% dei casi si riscontra eosinofilia periferica. Sono in genere colpite donne tra la terza e la quinta decade di vita. L’andamento è cronico.

L’eziologia dell’iperplasia angiolinfoide con eosinofilia è ancora poco chiara, anche se la malattia viene considerata dalla maggior parte degli autori un processo reattivo o di natura vascolare amartomatosa. La sua insorgenza è riportata a seguito di traumi e durante la gravidanza. Recentemente si è ipotizzato che rappresenti la forma di esordio di un linfoma T. Le terapie di scelta rimangono l’asportazione chirurgica e i corticosteroidi intralesionali.

Bibliografia

1. Martín-Granizo R. at al. Epithelioid hemangiomas of the maxillofacial area. A report of three cases and a review of the literature. Int J Oral Maxillofac Surg 1997;26:212-4.
2. Gonzalez-Cuyar L.F. et al. Angiolymphoid hyperplasia with eosinophilia developing in a patient with history of peripheral T-cell lymphoma: evidence for multicentric T-cell lymphoproliferative process. Diagn Pathol 2008;3:22

R. Gianotti
Istituto di Scienze Dermatologiche, Università degli Studi di Milano
U.O. Dermatologia, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano