keratoacanthoma is a rapidly evolving cutaneous tumor composed of keratinizing squamous cells originating from the supra - seboglandular portion of the hair follicle .
keratoacanthoma may be solitary or multiple but the most common form is the classical solitary variety , which occurs on the exposed body parts of the elderly person , and involutes by itself even if left untreated .
multiple keratoacanthomas , on the other hand , develop sporadically ( e.g. eruptive keratoacanthomas of the grzybowski type , or the familial syndromes like muir - torre syndrome , or its incomplete form , ferguson - smith syndrome ) .
keratoacanthoma centrifugum marginatum ( kcm ) is among the rare varieties and , in contrast to the classical variety , does not show any tendency of spontaneous regression .
lack of spontaneous regression is also a feature of another rare variant of keratoacanthoma , the giant keratoacanthoma , from which kcm is differentiated by the absence of downward vertical spread with destruction of the underlying tissue .
progressive peripheral extension with a raised rolled - out margin and atrophy at the center of the lesion is a characteristic feature of the kcm .
the most common site of kcm is reported to be the dorsum of the hands and legs .
the etiology of kcm is multifactorial , which includes chronic ultraviolet ray exposure , the smoking habit , and contact with chemical carcinogens like pitch , mineral oil , tar , etc .
the role of human papilloma virus ( hpv ) in keratoacanthoma remains inconclusive , with one study finding evidence of hpv infection by polymerase chain reaction , whereas another study failing to detect any virus material .
a 65-year - old healthy male , a cultivator by occupation , presented with a solitary painful plaque involving his left arm and forearm .
it started spontaneously four years previously as a hyperpigmented nodule on the extensor aspect of the left forearm , which was operated on by a local doctor .
the lesion recurred following the operation and gradually grew peripherally with healing of the center .
the patient could not recall any history of trauma preceding the onset of the lesion , neither was there any family history of a similar disorder . apart from tobacco smoking
, there was no significant history of drug addiction , ingestion of halogenated compounds , or contact with chemicals . on examination
, a large single plaque 3010 cm in size was found occupying the left forearm ( involving both dorsal and ventral aspects ) , the elbow , and the lower part of the left arm ( figure 1 ) .
the margin of the lesion was rolled out and interrupted , having hyperpigmented , firm , discrete , tender nodules and a cribriform pattern with comedonal orifices .
the nodules had a central depression and foul - smelling cheesy material could be squeezed out on application of firm pressure on these nodules ( figure 2 ) .
the center of the plaque was atrophic and depigmented with intervening areas of normal skin .
the lesion was not found to be adherent to the underlying structures and there was no regional lymphadenopathy or organomegaly . 

figure 1plaque with rolled - out interrupted margin and atrophic center with island of normal skin located on the extensor aspect of the left forearm and lower part of the left arm
. plaque with rolled - out interrupted margin and atrophic center with island of normal skin located on the extensor aspect of the left forearm and lower part of the left arm . 

figure 2close - up picture showing cheesy material exuding from ( after being compressed laterally ) a punctum overlying the margin of the lesion .
close - up picture showing cheesy material exuding from ( after being compressed laterally ) a punctum overlying the margin of the lesion .
hematocrit , platelet , and leukocyte counts , and hepatic and renal function tests were within normal limits . a chest x - ray and ecg showed no abnormality .
an x - ray of the left hand including wrist and elbow joints showed no bony involvement .
the culture from the cheesy material revealed the presence of a gram - negative organism belonging to proteus species . a biopsy taken from the margin of the lesion showed large irregularly shaped craters filled with keratin ( figure 3 ) and , from the base of the crater , irregular epidermal proliferations extending downward but not extending below the level of the sweat glands ( figure 4 ) . at the periphery of the epidermal proliferations
there was evidence of a thin layer of basophilic cells with the base of the crater containing epithelial pearls ( figure 5 ) and showing rich keratinization imparting a glassy appearance ( figure 6 ) . a mild to moderate degree of mononuclear cellular infiltrate was present within the dermis but mitotic figures were found rarely .
there was no evidence of granuloma and no fungal element could be detected with pas staining . 

figure 3histopathological section showing a large crater filled with keratin and having irregular epithelial proliferations extending into the papillary dermis .
the basal layer is intact with no evidence of cellular atypia ( hematoxylin and eosin stain ; 100 magnification ) .
histopathological section showing a large crater filled with keratin and having irregular epithelial proliferations extending into the papillary dermis .
the basal layer is intact with no evidence of cellular atypia ( hematoxylin and eosin stain ; 100 magnification ) . 

figure 4cross - section of the crater showing a large cavity filled with keratin and irregular epidermal proliferations extending downward from its base , but not extending below the level of the sweat gland ( hematoxylin and eosin stain ; 40 magnification ) .
cross - section of the crater showing a large cavity filled with keratin and irregular epidermal proliferations extending downward from its base , but not extending below the level of the sweat gland ( hematoxylin and eosin stain ; 40 magnification ) . 

figure 5histopathological section of the lateral wall of the epithelial proliferation showing a thin uninterrupted layer of basophilic cells and the base of the crater having epithelial pearls and well - keratinized cells giving a glassy appearance .
no abnormal mitotic figures are detected and the papillary dermis shows scattered mononuclear cell infiltrates ( hematoxylin and eosin stain ; 100 magnification ) .
histopathological section of the lateral wall of the epithelial proliferation showing a thin uninterrupted layer of basophilic cells and the base of the crater having epithelial pearls and well - keratinized cells giving a glassy appearance .
no abnormal mitotic figures are detected and the papillary dermis shows scattered mononuclear cell infiltrates ( hematoxylin and eosin stain ; 100 magnification ) . 

figure 6higher magnification of the epidermal proliferation showing an eosinophilic , glassy appearing cell mass , marginated by a 12 layer of basophilic nonkeratinized cells ( hematoxylin and eosin stain ; 400 magnification ) .
higher magnification of the epidermal proliferation showing an eosinophilic , glassy appearing cell mass , marginated by a 12 layer of basophilic nonkeratinized cells ( hematoxylin and eosin stain ; 400 magnification ) . 

figure 7six months after wide excision and repair of the nodules on the margins of the lesion showing the grafts ( near the wrist and above the elbow ) satisfactorily taken .
six months after wide excision and repair of the nodules on the margins of the lesion showing the grafts ( near the wrist and above the elbow ) satisfactorily taken .
the clinicopathological correlation confirmed the case to be kcm and the patient was started on acitretin ( initially 0.5 mg / kg / day then increasing the dose to 1 mg / kg / day after 15 days ) . despite treatment for three consecutive months , the lesion showed no signs of improvement and a few new nodules appeared near the elbow crease .
the nodules at the margin of the lesions were excised with a 1-cm margin , up to a depth of the antebrachial fascia .
postoperative graft uptake was satisfactory and the patient has been followed - up for the past six months , showing no signs of recurrence ( figure 5 ) .
kcm is a very rare type of keratoacanthoma , and a pubmed search produced 31 entries of kcm in the world literature since its first description in 1962 .
diagnosis of the condition was a real challenge in our case and meticulous clinical and histopathological examinations were required to differentiate it from several other conditions that closely mimic kcm .
the clinical differential diagnoses include squamous cell carcinoma ( scc ) , lupus vulgaris ( lv ) , botryomycosis , blastomycosis - like pyoderma ( blp ) , and pseudoepitheliomatous hyperplasia ( peh ) .
the fact that the lesion showed resolution in some places was a useful clinical clue in differentiating it from scc .
the presence of mitotic figures in our case can not be taken as a marker of scc as there were very few , although it has been reported that they may be associated with kcm . the large plaque with atrophy at the center of the lesion also prompted consideration of lv in the setting of the indian subcontinent , but the absence of an underlying tubercular granuloma helped us to exclude this condition .
the diagnostic dilemma was the finding of the presence of the proteus organism within the lesions , which is a feature of botryomycosis .
the absence of tumefaction or purulent discharge , with the histopathological finding failing to reveal any neutrophilic infiltration , grape - shaped granules , or splendore - hoeppli phenomenon , ruled out the possibility of botryomycosis .
in fact , bpl may present also with a large verrucous plaque with pseudoepitheliomatous hyperplasia . however , we easily ruled out this condition as there were no pustules demonstrated clinically and no suppuration was found on histopathology ; moreover , bpl usually affects immunosuppressed patients .
furthermore , peh could be ruled out by the fact that it was not preceded by any other skin lesion , and by the histopathological finding of epidermal hyperplasia restricted to above the level of the sweat glands and the presence of a large crater , all of which are unlikely in the case of phe .
after the exclusion of the clinical mimickers , kcm was diagnosed on the basis of classical clinical and histopathological findings .
the appearance of recurrent nodular skin lesions with central clearing and progressive peripheral spreading on the distal extremities , in the setting of the histopathological findings of large irregularly shaped craters filled with keratin , with irregular epidermal proliferation having a glassy appearance and not extending below the level of the sweat glands , was diagnostic of kcm .
the findings in our case were similar to those of previous case reports with the presence of large lesions and no tendency to spontaneous resolution .
the margin of the lesion showing multiple comedonal orifices giving rise to a cibriform pattern , as seen in our case , may represent a unique phenomenon of kcm .
we hypothesized that the typical appearance may arise as a result of sequential involvement of multiple adjacent hair follicles in a centrifugal fashion .
it is an interesting finding and , if future case reports of this rare variant of keratoacanthoma document the same feature , then this hypothesis will be validated .
however , making the diagnosis was not the end and therapy was also a challenge .
there are reports that kcm has been treated successfully with oral retinoids ; hence , we started oral acitretin .
after three months of high - dose therapy , it had to be abandoned because of no therapeutic improvement .
the decision was taken in favor of surgical intervention and wide local excision was planned , considering the fact that the patient showed recurrence following previous inadequate excision .
following our intervention , the patient is showing no recurrence , highlighting that surgical intervention can be adopted as the preferred mode of therapy for kcm , keeping in mind that a wide excision is performed to prevent subsequent recurrence .
 we describe a case of a 65-year - old male presenting with a large plaque with a rolled - out interrupted margin , atrophic center , and island of normal skin over the left arm . 
 it grew peripherally with central healing , and there was a history of recurrence after inadequate excision . 
 investigations ruled out other clinical mimickers ; namely , squamous cell carcinoma , lupus vulgaris , botryomycosis , and blastomycosis - like pyoderma . 
 histopathological sections showed irregularly shaped craters filled with keratin and epithelial pearl but no evidence of granuloma or cellular atypia . 
 clinicopathological correlation proved the lesion to be keratoacanthoma centrifugum marginatum ( kcm ) , a rare variant of keratoacanthoma , which spreads centrifugally , attains a huge size , and never involutes spontaneously . 
 treatment of kcm has been a problem always and , in our case , systemic retinoid ( acitretin for three months ) proved ineffective . 
 the patient also had a history of recurrence following surgical intervention previously , necessitating wide excision to achieve complete clearance of tumor cells . 
 hence , after failure of retinoid therapy , the decision of excision with a 1-centimeter margin was taken and the large defect was closed by a split thickness skin graft . 
 the graft uptake was satisfactory , and the patient is being followed - up presently and shows no signs of recurrence after six months , highlighting wide local excision as a useful treatment option . 