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Abortive keratoacanthoma: a hitherto unrecognised variant
Pathology (December 2010) 42(7), pp. 661–663
ANATOMICAL PATHOLOGY
Abortive keratoacanthoma: a hitherto unrecognised variant DAVID WEEDON*, DAVID BROOKS{, JONATHAN MALO{
AND
RICHARD WILLIAMSON*
*Skin Laboratory, Sullivan Nicolaides Pathology, Taringa, and {University of Queensland, Brisbane, Queensland, Australia
Summary Aims: To study the histological features of abortive keratoacanthoma, a variant that has only recently been recognised. Methods: A key word search of the database of our pathology practice was carried out for all keratoacanthomas (KAs) reported by one author (DW) over a 14-month period. These cases were then sorted into histological subtypes by age in decades. Results: A total of 3465 cases of KA were reported over this period, of which 582 (16.8%) were of the so-called abortive type. Abortive KAs are characterised by rapid growth and subsequent lichenoid regression at an early stage in their evolution. Lichenoid changes extend for a variable distance beyond the lesion. Conclusions: Abortive KA is a hitherto unrecognised variant of KA which may be misdiagnosed as squamous cell carcinoma despite its distinctive features. Lichenoid regression, rather than terminal differentiation, is the main mechanism of its involution. Key words: Keratoacanthoma, regression, lichenoid change. Received 14 May 2010, revised 10 July 2010, accepted 13 July 2010
INTRODUCTION Our long-term interest in keratoacanthomas (KAs) has been rekindled in recent years by the increasing trend in some overseas countries, particularly the United States and parts of Europe, to rebadge KA as ‘squamous cell carcinoma – keratoacanthoma type’.1 This move is driven, in part, by the medicolegal consequences of underdiagnosis of a squamoproliferative lesion. However, it risks overtreatment of KAs, particularly those with perineural or intravenous invasion, which we and others have shown previously to behave in a completely benign fashion.2,3 Three variants of KA are currently of special interest to us; all have been relatively neglected in the literature and in the practice of pathology: KA with perineural and intravenous invasion, KA in which squamous cell carcinoma develops,4 and abortive KA, the subject of this article. An abortive KA is a clinicopathological entity in which involution of the lesion commences at an early stage in its evolution, after a relatively short growth period. The growth of this variant is quite rapid reaching its maximum size in 2–3 weeks, approximately half the usual growth period. Clinically, there is a central exophytic nodular growth common to KAs of most types, with the addition usually of a
peripheral erythematous rim of slightly raised skin that extends for up to several mm or more beyond the nodular growth. This variant is able to be diagnosed clinically by several of our referrers, who are aware of this subtype. If the rim alone is biopsied, the appearances are those of a lichen planus-like keratosis, a characteristic component of the abortive KA. The nodular component of this abortive variant also shows lichenoid regression after a short period of active growth. Accordingly, abortive KAs rarely extend deeper than the mid-dermis, and a heavy lymphocytic infiltrate lies beneath the lesion and extends beyond it, in the manner of a lichen planus-like keratosis (Fig. 1–4). In a recent study of 3465 cases of KA reported by one author (DW), 582 (16.8%) were of this distinctive abortive variant.
MATERIALS AND METHODS The reports of all cases of KA reported by author (DW) over the 14 month period 1 January 2008 to 28 February 2009 were retrieved by a computergenerated word search for this entity. Consultation cases were not included. Two of the authors (JM and DB) then sorted the cases, by age in decades, into the following variants: KA alone, KA with superimposed SCC, KA with perineural invasion, keratoacanthoma centrifugum marginatum and abortive KA. If a KA was biopsied initially and then treated definitively by surgical excision or curette and cautery it was counted only once. Patients with more than one KA were encountered and these were separately distinguished. No ‘indeterminate squamoproliferative lesions’ were diagnosed as in the few cases in which an equivocal diagnosis was made on punch biopsy, the subsequent excision allowed specific categorisation of the lesion. Two cases of KA-like prurigo nodularis were excluded. The criteria used for the diagnosis of KA and the variants listed are given in Weedon’s Skin Pathology.5 The most important criterion for the diagnosis of KA is the pattern of keratinisation of the cells which are large and pale pink with a hyaline appearance, although the bottom few layers of recently formed cells do not show these changes.
RESULTS A total of 3465 cases of KA were reported over this 14 month period, arising in 3307 patients. Of the 3465 cases, 200 cases had SCC arising within them, eight cases had perineural invasion (7 pure KAs and 1 KA with SCC ‘transformation’), four cases were of centrifugum marginatum type and 582 (16.8%) were abortive in type. The 582 abortive cases occurred in 562 patients of whom 313 (59.4%) were males and 249 (40.6%) were females. Of the 582 abortive cases, 342 occurred in patients 570 years
Print ISSN 0031-3025/Online ISSN 1465-3931 # 2010 The Royal College of Pathologists of Australasia DOI: 10.3109/00313025.2010.522176
662
WEEDON et al.
Pathology (2010), 42(7), December
Fig. 1 Abortive keratoacanthoma. It lacks the usual symmetry and buttressing of the usual keratoacanthoma. A lichenoid lymphocytic infiltrate is present in the base of the lesion; it extends peripherally beyond the nodular portion.
Fig. 3 Abortive keratoacanthoma. A further case showing a keratin plug, lack of symmetry and buttressing. The lichenoid infiltrate is less than is usual.
Fig. 2 Abortive keratoacanthoma. The typical pattern of keratinisation is present in the constituent cells. A lichenoid infiltrate is present in the base of the lesion.
Fig. 4 A late-stage abortive keratoacanthoma. It combines some terminal differentiation with lichenoid regression. The lichenoid infiltrate extends in the usual fashion, well beyond the lesion.
of age, 152 occurred in patients 70–79 years, 81 occurred in patients 80–89 years and seven lesions arose in patients 90 years of age and over. Abortive KAs constituted 22.3% of KAs in patients less than 70 years, but only 11.5% of KAs in patients 80 years of age and older. The site of occurrence of this variant mirrored that of the usual variant with 343 (58.9%) on the lower limbs, 153 (26.2%) on the upper limbs, 34 (5.8%) on the head and neck and 48 (8.2%) on the trunk, mainly the shoulders. In four cases, the site was not specified. Of the 582 cases, 310 were definitive excision specimens, 249 were shaves (including saucerisations), and the remainder (23 cases) were punch biopsies. No formal follow-up was done on the cases that were shaved or biopsied but it was our anecdotal impression that nothing further was done on cases in which the shave biopsy had clear margins or just a nest or two involving the deep edge.
DISCUSSION There are four reasons why abortive KAs deserve separate recognition: (1) they have distinctive clinicopathological features that allow them to be distinguished both clinically and histologically; (2) there is a risk that if a 2 mm biopsy is taken from the erythematous periphery, a misdiagnosis of lichen planus-like keratosis (lichenoid keratosis) will be made; (3) misdiagnosis as an SCC is common because the lesions often lack the symmetry and buttressing of the more usual KA; and (4) their mode of regression differs from that of most other KAs. Each of these points will be discussed in turn. The distinctive clinicopathological features of this entity have already been outlined in the Introduction. They include a shorter and faster growth phase followed by involution after as little as 4–6 weeks growth. They are characterised histologically by smaller, less well-developed lesions with conspicuous lichenoid regression extending beyond the lesion. One author (DW) has seen several cases
ABORTIVE KERATOACANTHOMA
in which only a lichenoid lesion was present on biopsy, because the periphery and not the nodular component of the lesion had been biopsied. We have seen cases misdiagnosed as SCC because the lesions did not possess the prototypical features of the usual variant of KA. The regression of abortive KA occurs predominantly by lichenoid lymphocytic regression, whereas the predominant method by which the regression of the classic KA occurs is by terminal differentiation of the cells with the formation of a keratin plug and its eventual extrusion. Some spontaneous apoptosis also contributes to this regression. This process was known several decades ago as ‘round red cell degeneration’.6 Lichenoid lymphocytic regression is a minor component of the regression of the usual KA in contrast to its pivotal role in abortive variants. Perhaps the term ‘lichenoid keratoacanthoma’ would better reflect these histological features. The reduced incidence of abortive KAs in older persons may be due to the reduced cellular immunity found in this group.
663
We hope that highlighting this variant of KA will lead to its better recognition. Address for correspondence: Dr D. Weedon, Skin Laboratory, Sullivan Nicolaides Pathology, 134 Whitmore Street, Taringa, Brisbane, Qld 4068, Australia. E-mail: [email protected]
References 1. Hurt MA. Keratoacanthoma vs squamous cell carcinoma in contrast with keratoacanthoma is squamous cell carcinoma. J Cutan Pathol 2004; 31: 291–3. 2. Godbolt AM, Sullivan JJ, Weedon D. Keratoacanthoma with perineural invasion, a report of 40 cases. Australas J Dermatol 2001; 42: 168–71. 3. Cooper PH, Wolfe JT III. Perioral keratoacanthomas with extensive perineural invasion and intravenous growth. Arch Dermatol 1988; 124: 1397–401. 4. Weedon DD, Malo J, Brooks D, Williamson R. Squamous cell carcinoma arising in keratoacanthoma: a neglected phenomenon in the elderly. Am J Dermatopathol 2010; 32: 423–6. 5. Weedon D. Weedon’s Skin Pathology. 3rd ed. Edinburgh: Elsevier, 2010; 702–8. 6. McNulty JR, Sommers SC. Keratoacanthoma as a surgical pathologic entity. Surg Gynecol Obstet 1954; 104: 663–8.
ANATOMICAL PATHOLOGY
Abortive keratoacanthoma: a hitherto unrecognised variant DAVID WEEDON*, DAVID BROOKS{, JONATHAN MALO{
AND
RICHARD WILLIAMSON*
*Skin Laboratory, Sullivan Nicolaides Pathology, Taringa, and {University of Queensland, Brisbane, Queensland, Australia
Summary Aims: To study the histological features of abortive keratoacanthoma, a variant that has only recently been recognised. Methods: A key word search of the database of our pathology practice was carried out for all keratoacanthomas (KAs) reported by one author (DW) over a 14-month period. These cases were then sorted into histological subtypes by age in decades. Results: A total of 3465 cases of KA were reported over this period, of which 582 (16.8%) were of the so-called abortive type. Abortive KAs are characterised by rapid growth and subsequent lichenoid regression at an early stage in their evolution. Lichenoid changes extend for a variable distance beyond the lesion. Conclusions: Abortive KA is a hitherto unrecognised variant of KA which may be misdiagnosed as squamous cell carcinoma despite its distinctive features. Lichenoid regression, rather than terminal differentiation, is the main mechanism of its involution. Key words: Keratoacanthoma, regression, lichenoid change. Received 14 May 2010, revised 10 July 2010, accepted 13 July 2010
INTRODUCTION Our long-term interest in keratoacanthomas (KAs) has been rekindled in recent years by the increasing trend in some overseas countries, particularly the United States and parts of Europe, to rebadge KA as ‘squamous cell carcinoma – keratoacanthoma type’.1 This move is driven, in part, by the medicolegal consequences of underdiagnosis of a squamoproliferative lesion. However, it risks overtreatment of KAs, particularly those with perineural or intravenous invasion, which we and others have shown previously to behave in a completely benign fashion.2,3 Three variants of KA are currently of special interest to us; all have been relatively neglected in the literature and in the practice of pathology: KA with perineural and intravenous invasion, KA in which squamous cell carcinoma develops,4 and abortive KA, the subject of this article. An abortive KA is a clinicopathological entity in which involution of the lesion commences at an early stage in its evolution, after a relatively short growth period. The growth of this variant is quite rapid reaching its maximum size in 2–3 weeks, approximately half the usual growth period. Clinically, there is a central exophytic nodular growth common to KAs of most types, with the addition usually of a
peripheral erythematous rim of slightly raised skin that extends for up to several mm or more beyond the nodular growth. This variant is able to be diagnosed clinically by several of our referrers, who are aware of this subtype. If the rim alone is biopsied, the appearances are those of a lichen planus-like keratosis, a characteristic component of the abortive KA. The nodular component of this abortive variant also shows lichenoid regression after a short period of active growth. Accordingly, abortive KAs rarely extend deeper than the mid-dermis, and a heavy lymphocytic infiltrate lies beneath the lesion and extends beyond it, in the manner of a lichen planus-like keratosis (Fig. 1–4). In a recent study of 3465 cases of KA reported by one author (DW), 582 (16.8%) were of this distinctive abortive variant.
MATERIALS AND METHODS The reports of all cases of KA reported by author (DW) over the 14 month period 1 January 2008 to 28 February 2009 were retrieved by a computergenerated word search for this entity. Consultation cases were not included. Two of the authors (JM and DB) then sorted the cases, by age in decades, into the following variants: KA alone, KA with superimposed SCC, KA with perineural invasion, keratoacanthoma centrifugum marginatum and abortive KA. If a KA was biopsied initially and then treated definitively by surgical excision or curette and cautery it was counted only once. Patients with more than one KA were encountered and these were separately distinguished. No ‘indeterminate squamoproliferative lesions’ were diagnosed as in the few cases in which an equivocal diagnosis was made on punch biopsy, the subsequent excision allowed specific categorisation of the lesion. Two cases of KA-like prurigo nodularis were excluded. The criteria used for the diagnosis of KA and the variants listed are given in Weedon’s Skin Pathology.5 The most important criterion for the diagnosis of KA is the pattern of keratinisation of the cells which are large and pale pink with a hyaline appearance, although the bottom few layers of recently formed cells do not show these changes.
RESULTS A total of 3465 cases of KA were reported over this 14 month period, arising in 3307 patients. Of the 3465 cases, 200 cases had SCC arising within them, eight cases had perineural invasion (7 pure KAs and 1 KA with SCC ‘transformation’), four cases were of centrifugum marginatum type and 582 (16.8%) were abortive in type. The 582 abortive cases occurred in 562 patients of whom 313 (59.4%) were males and 249 (40.6%) were females. Of the 582 abortive cases, 342 occurred in patients 570 years
Print ISSN 0031-3025/Online ISSN 1465-3931 # 2010 The Royal College of Pathologists of Australasia DOI: 10.3109/00313025.2010.522176
662
WEEDON et al.
Pathology (2010), 42(7), December
Fig. 1 Abortive keratoacanthoma. It lacks the usual symmetry and buttressing of the usual keratoacanthoma. A lichenoid lymphocytic infiltrate is present in the base of the lesion; it extends peripherally beyond the nodular portion.
Fig. 3 Abortive keratoacanthoma. A further case showing a keratin plug, lack of symmetry and buttressing. The lichenoid infiltrate is less than is usual.
Fig. 2 Abortive keratoacanthoma. The typical pattern of keratinisation is present in the constituent cells. A lichenoid infiltrate is present in the base of the lesion.
Fig. 4 A late-stage abortive keratoacanthoma. It combines some terminal differentiation with lichenoid regression. The lichenoid infiltrate extends in the usual fashion, well beyond the lesion.
of age, 152 occurred in patients 70–79 years, 81 occurred in patients 80–89 years and seven lesions arose in patients 90 years of age and over. Abortive KAs constituted 22.3% of KAs in patients less than 70 years, but only 11.5% of KAs in patients 80 years of age and older. The site of occurrence of this variant mirrored that of the usual variant with 343 (58.9%) on the lower limbs, 153 (26.2%) on the upper limbs, 34 (5.8%) on the head and neck and 48 (8.2%) on the trunk, mainly the shoulders. In four cases, the site was not specified. Of the 582 cases, 310 were definitive excision specimens, 249 were shaves (including saucerisations), and the remainder (23 cases) were punch biopsies. No formal follow-up was done on the cases that were shaved or biopsied but it was our anecdotal impression that nothing further was done on cases in which the shave biopsy had clear margins or just a nest or two involving the deep edge.
DISCUSSION There are four reasons why abortive KAs deserve separate recognition: (1) they have distinctive clinicopathological features that allow them to be distinguished both clinically and histologically; (2) there is a risk that if a 2 mm biopsy is taken from the erythematous periphery, a misdiagnosis of lichen planus-like keratosis (lichenoid keratosis) will be made; (3) misdiagnosis as an SCC is common because the lesions often lack the symmetry and buttressing of the more usual KA; and (4) their mode of regression differs from that of most other KAs. Each of these points will be discussed in turn. The distinctive clinicopathological features of this entity have already been outlined in the Introduction. They include a shorter and faster growth phase followed by involution after as little as 4–6 weeks growth. They are characterised histologically by smaller, less well-developed lesions with conspicuous lichenoid regression extending beyond the lesion. One author (DW) has seen several cases
ABORTIVE KERATOACANTHOMA
in which only a lichenoid lesion was present on biopsy, because the periphery and not the nodular component of the lesion had been biopsied. We have seen cases misdiagnosed as SCC because the lesions did not possess the prototypical features of the usual variant of KA. The regression of abortive KA occurs predominantly by lichenoid lymphocytic regression, whereas the predominant method by which the regression of the classic KA occurs is by terminal differentiation of the cells with the formation of a keratin plug and its eventual extrusion. Some spontaneous apoptosis also contributes to this regression. This process was known several decades ago as ‘round red cell degeneration’.6 Lichenoid lymphocytic regression is a minor component of the regression of the usual KA in contrast to its pivotal role in abortive variants. Perhaps the term ‘lichenoid keratoacanthoma’ would better reflect these histological features. The reduced incidence of abortive KAs in older persons may be due to the reduced cellular immunity found in this group.
663
We hope that highlighting this variant of KA will lead to its better recognition. Address for correspondence: Dr D. Weedon, Skin Laboratory, Sullivan Nicolaides Pathology, 134 Whitmore Street, Taringa, Brisbane, Qld 4068, Australia. E-mail: [email protected]
References 1. Hurt MA. Keratoacanthoma vs squamous cell carcinoma in contrast with keratoacanthoma is squamous cell carcinoma. J Cutan Pathol 2004; 31: 291–3. 2. Godbolt AM, Sullivan JJ, Weedon D. Keratoacanthoma with perineural invasion, a report of 40 cases. Australas J Dermatol 2001; 42: 168–71. 3. Cooper PH, Wolfe JT III. Perioral keratoacanthomas with extensive perineural invasion and intravenous growth. Arch Dermatol 1988; 124: 1397–401. 4. Weedon DD, Malo J, Brooks D, Williamson R. Squamous cell carcinoma arising in keratoacanthoma: a neglected phenomenon in the elderly. Am J Dermatopathol 2010; 32: 423–6. 5. Weedon D. Weedon’s Skin Pathology. 3rd ed. Edinburgh: Elsevier, 2010; 702–8. 6. McNulty JR, Sommers SC. Keratoacanthoma as a surgical pathologic entity. Surg Gynecol Obstet 1954; 104: 663–8.