Abstracts
The authors describe a case of a female patient with Acral Pseudolymphomatous Angiokeratoma of Children, known as APACHE. It is a rare benign cutaneous disease, of unknown etiology, characterized by multiple, asymptomatic erythematous-violaceous papules and nodules, usually located unilaterally with acral distribution. Today, this denomination is questionable, since there are published reports of this disease in adults and in different locations. Clinically, it is similar to an angiokeratoma, whereas hystologically, it corresponds to a distinct type of pseudolymphoma. The immunohistochemical study is required to distinguish APACHE from cutaneous lymphoma.
Child; Extremities; Hemangioma; Pseudolymphoma
Relata-se o caso de uma paciente com diagnóstico de angioqueratoma pseudolinfomatoso acral, conhecido por sua sigla em inglês APACHE - Acral Pseudolymphomatous Angiokeratoma of Children. É uma doença cutânea benigna, rara, de etiologia desconhecida, caracterizada por múltiplas pápulas e nódulos eritêmato-violáceos assintomáticos, de localização geralmente unilateral e acral. Atualmente, questiona-se esta denominação, já que há relatos na literatura do quadro em adultos e em outras localizações. Clinicamente, é similar a um angioqueratoma, porém, histologicamente, corresponde a um tipo distinto de pseudolinfoma. O estudo imuno-histoquímico é necessário para diferenciação dos linfomas cutâneos.
Criança; Extremidades; Hemangioma; Pseudolinfoma
INTRODUCTION
Acral pseudolymphomatous angiokeratoma is a rare benign, cutaneous disease, mostly
affecting children aged between 2 and 13. It is characterized by multiple asymptomatic
erythematous-violaceous papules and nodules, usually located unilaterally with acral
distribution. 11. Ramsay B, Dahl MC, Malcolm AJ, Wilson-Jones E. Acral
pseudolymphomatous angiokeratoma of children. Arch Dermatol.
1990;126:1524-5.
2. Freire FMZ, Filho JBS, Cintra LC, Diniz LM. Acral pseudolymphomatous
angiokeratoma - a case report. An Bras Dermatol. 2006;81:S277-80.
3. Okada M, Funayama M, Tanita M, Kudoh K, Aiba S, Tagami H. Acral
angiokeratoma-like pseudolymphoma: one adolescent and two adults. J Am Acad Dermatol.
2001;45:S209-11.
4. Murakami T, Ohtsuki M, Nakagawa H. Acral pseudolymphomatous
angiokeratoma of children: a pseudolymphoma rather than an angiokeratoma. Br J
Dermatol. 2001;145:512-4.
5. Hagari Y, Hagari S, Kambe N, Kawaguchi T, Nakamoto S, Mihara M. Acral
pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses
of the infiltrating cells. J Cutan Pathol. 2002;29:313-8.-66. Chedraoui A, Malek J, Tamraz H, Zaynoun S, Kibbi AG, Ghosn S. Acral
pseudolynphomatous angiokeratoma of children in an elderly man: report of a case and
review of the literature. Int J Dermatol. 2010;49:184-8. Initially considered a vascular malformation, today it is classed
as a distinct type of pseudolymphoma. 33. Okada M, Funayama M, Tanita M, Kudoh K, Aiba S, Tagami H. Acral
angiokeratoma-like pseudolymphoma: one adolescent and two adults. J Am Acad Dermatol.
2001;45:S209-11.,44. Murakami T, Ohtsuki M, Nakagawa H. Acral pseudolymphomatous
angiokeratoma of children: a pseudolymphoma rather than an angiokeratoma. Br J
Dermatol. 2001;145:512-4. It is known by the
acronym APACHE (Acral Pseudolymphomatous Angiokeratoma of Children) and was described
for the first time by Ramsay in 1988.66. Chedraoui A, Malek J, Tamraz H, Zaynoun S, Kibbi AG, Ghosn S. Acral
pseudolynphomatous angiokeratoma of children in an elderly man: report of a case and
review of the literature. Int J Dermatol. 2010;49:184-8. Currently,
this denomination is under debate, as there are reported cases in the literature of
adults with the condition, located in other parts of the integument. 11. Ramsay B, Dahl MC, Malcolm AJ, Wilson-Jones E. Acral
pseudolymphomatous angiokeratoma of children. Arch Dermatol.
1990;126:1524-5.
2. Freire FMZ, Filho JBS, Cintra LC, Diniz LM. Acral pseudolymphomatous
angiokeratoma - a case report. An Bras Dermatol. 2006;81:S277-80.
3. Okada M, Funayama M, Tanita M, Kudoh K, Aiba S, Tagami H. Acral
angiokeratoma-like pseudolymphoma: one adolescent and two adults. J Am Acad Dermatol.
2001;45:S209-11.
4. Murakami T, Ohtsuki M, Nakagawa H. Acral pseudolymphomatous
angiokeratoma of children: a pseudolymphoma rather than an angiokeratoma. Br J
Dermatol. 2001;145:512-4.
5. Hagari Y, Hagari S, Kambe N, Kawaguchi T, Nakamoto S, Mihara M. Acral
pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses
of the infiltrating cells. J Cutan Pathol. 2002;29:313-8.-66. Chedraoui A, Malek J, Tamraz H, Zaynoun S, Kibbi AG, Ghosn S. Acral
pseudolynphomatous angiokeratoma of children in an elderly man: report of a case and
review of the literature. Int J Dermatol. 2010;49:184-8. Its etiology remains unknown. Histopathological exams reveal preserved
epidermis and dense lymphocytic infiltrate in the dermis, permeating structures of the
conjunctive tissue, affecting (or not) the cutaneous annexes. The immunohistochemical
study is necessary in order to distinguish the cutaneous lymphomas.11. Ramsay B, Dahl MC, Malcolm AJ, Wilson-Jones E. Acral
pseudolymphomatous angiokeratoma of children. Arch Dermatol.
1990;126:1524-5.
2. Freire FMZ, Filho JBS, Cintra LC, Diniz LM. Acral pseudolymphomatous
angiokeratoma - a case report. An Bras Dermatol. 2006;81:S277-80.
3. Okada M, Funayama M, Tanita M, Kudoh K, Aiba S, Tagami H. Acral
angiokeratoma-like pseudolymphoma: one adolescent and two adults. J Am Acad Dermatol.
2001;45:S209-11.
4. Murakami T, Ohtsuki M, Nakagawa H. Acral pseudolymphomatous
angiokeratoma of children: a pseudolymphoma rather than an angiokeratoma. Br J
Dermatol. 2001;145:512-4.
5. Hagari Y, Hagari S, Kambe N, Kawaguchi T, Nakamoto S, Mihara M. Acral
pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses
of the infiltrating cells. J Cutan Pathol. 2002;29:313-8.
6. Chedraoui A, Malek J, Tamraz H, Zaynoun S, Kibbi AG, Ghosn S. Acral
pseudolynphomatous angiokeratoma of children in an elderly man: report of a case and
review of the literature. Int J Dermatol. 2010;49:184-8.-77. Tokuda Y, Arakura F, Murata H, Koga H, Kawachi S, Nakazawa K. Acral
pseudolynphomatous angiokeratoma of children: A case report with immunohistochemical
study of antipodoplanin antigen. Am J Dermatopathol.
2012;34:e128-32. The elective
therapeutic choice is total excision of lesions but intralesional corticotherapy,
cryotherapy and radiotherapy are also described, though they entail recurrence.22. Freire FMZ, Filho JBS, Cintra LC, Diniz LM. Acral pseudolymphomatous
angiokeratoma - a case report. An Bras Dermatol. 2006;81:S277-80.
CASE REPORT
White, female patient, aged 11, complaining of "small lumps on the left wrist since the age of two". The dermatological exam revealed erythematous-violaceous papules on the left wrist, which appeared fainter during the vitropression test (Figure 1). The condition had been evolving for 9 years, without any changes in clinical characteristics, local symptomatology or previous trauma. The histopathological exam revealed an integral epidermis without atypia; and, in the dermis, inflammatory infiltrate of superficial and deep, perivascular location, around the pilo-erector muscles, hair follicles, eccrine glands and nerves (Figures 2 and 3A). The infiltrate was made up of lymphocytes, some histiocytes, a moderate number of plasmocytes and small basophilic granulations in the cytoplasmas of the histiocytic cells. Infiltration was noticed in the hypodermal lobules. The search for alcohol-acid resistant bacilli using the Ziehl-Neelsen staining procedure culminated in a negative result. In regard to the inflammatory infiltrate, abundant in plasmocytes, a clinical and laboratory investigation was conducted to rule out leishmaniasis and syphilis, with the following findings: non-reactive VDRL and FTA-Abs results (Figure 3B). Surveys for micobacteria, treponema and leishmania, by immunohistochemistry, produced negative results. In addition: hemogram, hepatic and renal function, ESR, dosage of immunoglobulins and protein electrophoresis, without changes.
A. Infiltrate occupying the deep dermis (HE, 100x); B. Infiltrate composed of plasmocytes (HE, 400x)
Thus, total excision of the lesions was initiated, to diagnostic and therapeutic ends. The histopathological exam revealed the same histopatholoogical pattern as before. The immunohistochemical study of the biopsy material revealed histological characteristics of dermal lymphoid proliferation of small, perivascular and adnexal, T and B lymphocytes, with a low proliferative index (Figure 4 and Chart 1).
The patient is undergoing outpatient follow-up, with no signs of recurrence at present.
DISCUSSION
Acral pseudolymphomatous angiokeratoma, known by the acronym APACHE (Acral Pseudolymphomatous Angiokeratoma of Children), is a rare entity, first described by Ramsay et al in 1988. Since then, approximately 25 cases have been described in the literature.77. Tokuda Y, Arakura F, Murata H, Koga H, Kawachi S, Nakazawa K. Acral pseudolynphomatous angiokeratoma of children: A case report with immunohistochemical study of antipodoplanin antigen. Am J Dermatopathol. 2012;34:e128-32.
Initially considered a vascular malformation, today it is classed as a distinct type of pseudolymphoma. Immunohistochemical studies of cell markers and gene receptors using Southern blotting analysis have shown the poyclonal nature of the cellular infiltrate.77. Tokuda Y, Arakura F, Murata H, Koga H, Kawachi S, Nakazawa K. Acral pseudolynphomatous angiokeratoma of children: A case report with immunohistochemical study of antipodoplanin antigen. Am J Dermatopathol. 2012;34:e128-32.
Its etiology remains unknown. Many authors consider that terms such as "papular angiolymphoid hyperplasia", "acral angiokeratoma-like pseudolymphoma" and "pseudolymphomatous angiokeratoma", are more appropriate given that there have been cases involving dif ferent locations and age groups.22. Freire FMZ, Filho JBS, Cintra LC, Diniz LM. Acral pseudolymphomatous angiokeratoma - a case report. An Bras Dermatol. 2006;81:S277-80.,66. Chedraoui A, Malek J, Tamraz H, Zaynoun S, Kibbi AG, Ghosn S. Acral pseudolynphomatous angiokeratoma of children in an elderly man: report of a case and review of the literature. Int J Dermatol. 2010;49:184-8.
Clinically, it is characterized by asymptomatic, grouped erythematous-violaceous papules
and nodules, of angiomatous character and a keratotic surface, located mainly in the
extremities of children aged between 2 and 13.11. Ramsay B, Dahl MC, Malcolm AJ, Wilson-Jones E. Acral
pseudolymphomatous angiokeratoma of children. Arch Dermatol.
1990;126:1524-5.
2. Freire FMZ, Filho JBS, Cintra LC, Diniz LM. Acral pseudolymphomatous
angiokeratoma - a case report. An Bras Dermatol. 2006;81:S277-80.
3. Okada M, Funayama M, Tanita M, Kudoh K, Aiba S, Tagami H. Acral
angiokeratoma-like pseudolymphoma: one adolescent and two adults. J Am Acad Dermatol.
2001;45:S209-11.
4. Murakami T, Ohtsuki M, Nakagawa H. Acral pseudolymphomatous
angiokeratoma of children: a pseudolymphoma rather than an angiokeratoma. Br J
Dermatol. 2001;145:512-4.
5. Hagari Y, Hagari S, Kambe N, Kawaguchi T, Nakamoto S, Mihara M. Acral
pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses
of the infiltrating cells. J Cutan Pathol. 2002;29:313-8.-66. Chedraoui A, Malek J, Tamraz H, Zaynoun S, Kibbi AG, Ghosn S. Acral
pseudolynphomatous angiokeratoma of children in an elderly man: report of a case and
review of the literature. Int J Dermatol. 2010;49:184-8.
In a recent review of reported APACHE cases, Tokuda et al found that 77% of patients were female, 52% of lesions were acral and 70% of the affected individuals were made up of children and adolescents.77. Tokuda Y, Arakura F, Murata H, Koga H, Kawachi S, Nakazawa K. Acral pseudolynphomatous angiokeratoma of children: A case report with immunohistochemical study of antipodoplanin antigen. Am J Dermatopathol. 2012;34:e128-32.
Histologically, it presents with dense inflammatory infiltrate made up of lymphocytes, histiocytes, plasmocytes, multinucleated giant cells and a varying number of eosinophils (Chart 2).55. Hagari Y, Hagari S, Kambe N, Kawaguchi T, Nakamoto S, Mihara M. Acral pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses of the infiltrating cells. J Cutan Pathol. 2002;29:313-8.-66. Chedraoui A, Malek J, Tamraz H, Zaynoun S, Kibbi AG, Ghosn S. Acral pseudolynphomatous angiokeratoma of children in an elderly man: report of a case and review of the literature. Int J Dermatol. 2010;49:184-8.The infiltrate may (or not) affect annexes. Histological changes can affect the epidermis, revealing variable inflammatory changes such as exocytosis, vacuolar changes, spongiosis and eosinophilic bodies, though the meaning of these histological changes is still unknown.77. Tokuda Y, Arakura F, Murata H, Koga H, Kawachi S, Nakazawa K. Acral pseudolynphomatous angiokeratoma of children: A case report with immunohistochemical study of antipodoplanin antigen. Am J Dermatopathol. 2012;34:e128-32.
An immunohistochemical study is needed to rule out cutaneous lymphomas.22. Freire FMZ, Filho JBS, Cintra LC, Diniz LM. Acral pseudolymphomatous angiokeratoma - a case report. An Bras Dermatol. 2006;81:S277-80.It reveals B and T lymphocytes (CD4 and CD8) staining.44. Murakami T, Ohtsuki M, Nakagawa H. Acral pseudolymphomatous angiokeratoma of children: a pseudolymphoma rather than an angiokeratoma. Br J Dermatol. 2001;145:512-4.-55. Hagari Y, Hagari S, Kambe N, Kawaguchi T, Nakamoto S, Mihara M. Acral pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses of the infiltrating cells. J Cutan Pathol. 2002;29:313-8. Some reports indicate a predominance of T cells over B cells in the adult population, while the reverse is reported among the pediatric population.66. Chedraoui A, Malek J, Tamraz H, Zaynoun S, Kibbi AG, Ghosn S. Acral pseudolynphomatous angiokeratoma of children in an elderly man: report of a case and review of the literature. Int J Dermatol. 2010;49:184-8.Studies with polymerase chain reaction (PCR) showed the polyclonality of the inflammatory infiltrate, thus suggesting the reactional process of this entity.44. Murakami T, Ohtsuki M, Nakagawa H. Acral pseudolymphomatous angiokeratoma of children: a pseudolymphoma rather than an angiokeratoma. Br J Dermatol. 2001;145:512-4.,55. Hagari Y, Hagari S, Kambe N, Kawaguchi T, Nakamoto S, Mihara M. Acral pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses of the infiltrating cells. J Cutan Pathol. 2002;29:313-8.-66. Chedraoui A, Malek J, Tamraz H, Zaynoun S, Kibbi AG, Ghosn S. Acral pseudolynphomatous angiokeratoma of children in an elderly man: report of a case and review of the literature. Int J Dermatol. 2010;49:184-8.
Tokuda et al., through an immunostaining study of the lesion's vessels, obtained positive results for specific markers of the endothelium of the lymphatic vessels (podoplanin) and blood vessels (CD 34).
Linking these findings to the epidemiology of the disease, they again considered the hypothesis that the histogenesis of APACHE could be a type of vascular malformation or hemangioma.77. Tokuda Y, Arakura F, Murata H, Koga H, Kawachi S, Nakazawa K. Acral pseudolynphomatous angiokeratoma of children: A case report with immunohistochemical study of antipodoplanin antigen. Am J Dermatopathol. 2012;34:e128-32.
The elective therapeutic choice is total excision of the lesion, but intralesional corticotherapy, cryotherapy and radiotherapy are also described, though they entail recurrence.22. Freire FMZ, Filho JBS, Cintra LC, Diniz LM. Acral pseudolymphomatous angiokeratoma - a case report. An Bras Dermatol. 2006;81:S277-80.
REFERENCES
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1Ramsay B, Dahl MC, Malcolm AJ, Wilson-Jones E. Acral pseudolymphomatous angiokeratoma of children. Arch Dermatol. 1990;126:1524-5.
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2Freire FMZ, Filho JBS, Cintra LC, Diniz LM. Acral pseudolymphomatous angiokeratoma - a case report. An Bras Dermatol. 2006;81:S277-80.
-
3Okada M, Funayama M, Tanita M, Kudoh K, Aiba S, Tagami H. Acral angiokeratoma-like pseudolymphoma: one adolescent and two adults. J Am Acad Dermatol. 2001;45:S209-11.
-
4Murakami T, Ohtsuki M, Nakagawa H. Acral pseudolymphomatous angiokeratoma of children: a pseudolymphoma rather than an angiokeratoma. Br J Dermatol. 2001;145:512-4.
-
5Hagari Y, Hagari S, Kambe N, Kawaguchi T, Nakamoto S, Mihara M. Acral pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses of the infiltrating cells. J Cutan Pathol. 2002;29:313-8.
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6Chedraoui A, Malek J, Tamraz H, Zaynoun S, Kibbi AG, Ghosn S. Acral pseudolynphomatous angiokeratoma of children in an elderly man: report of a case and review of the literature. Int J Dermatol. 2010;49:184-8.
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7Tokuda Y, Arakura F, Murata H, Koga H, Kawachi S, Nakazawa K. Acral pseudolynphomatous angiokeratoma of children: A case report with immunohistochemical study of antipodoplanin antigen. Am J Dermatopathol. 2012;34:e128-32.
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* Study undertaken at the University Hospital of Taubaté - University of Taubaté (HUT-UNITAU) - Taubaté (SP), Brazil.
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Financial Support: None
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Conflict of Interest: None
Publication Dates
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Publication in this collection
Nov-Dec 2013
History
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Received
08 Jan 2013 -
Accepted
25 Jan 2013