T. Shulaia1, N. Kiladze2, A. Miriamidze3
1Medical Center “Marjani”
2Tbilisi State Medical University
3Pathology Research Center
Introduction. Skin tumors are one of the most important topics in dermatology. Due to the very complex anatomy of skin, these tumors have numerous types and subtypes. The incidence of benign skin tumors is high. It is important to recognize benign tumors for excellent prevention of skin cancer. Advanced diagnostic technique of skin tumors such as dermoscopy is very useful and shows high correlation with histopathology. Dermoscopic recognition of benign tumors may help to avoid unnecessary biopsies or surgical excision. The following article provides a brief overview of the literature and presents 2 cases of two different benign tumors. One of them is a clear cell acanthoma; originally it was thought that it is a rare benign epidermal tumor of unknown etiology, however, recent studies suggest that it is a reactive inflammatory dermatosis; and the other one – pseudolymphoma which is a reactive lymphocytic proliferation appearing in the skin and resembling a malignant lymphoma [17, 19]. Both of them are rare and benign, but they present such a problem as for differentiation as well for a possibility of pseudolymphoma to transform into malignant lymphoma. Distinguishing between cutaneous pseudolymphoma and true cutaneous lymphoma requires the complete synthesis of clinical, histopathologic, immunohistochemical, and molecular data; in many situations, patients need to be followed over time (particularly patients who present with a solitary small lesion) to determine which diagnosis fits best, especially given that many cutaneous lymphomas can take months to years to fully manifest themselves clinically .
The aim of the study is the analysis of the overview of the accessible literature and description of two clinical cases of skin tumors from the own practice.
Мaterials and methods. Content analysis, method of systemic comparative analysis, bibliosemantic method of studying actual scientific researches concerning the practice of noninvasive methods of evaluation were used. The search for sources was carried out in scientific meteorological databases: PubMedNCBI, Medline, CochraneLibrary, EMBASE, ResearchGate by keywords: “skin tumors”, “clear cell acanthoma”, “pseudolymphoma”, “dermatoscopy”.
Digital dermoscopic images were captured with a dermatoscope (DermLite DL3 dermatoscope) mounted on a digital camera (Galaxy S4 Samsung Corporation). Ultrasound gel was used for immersion dermatoscopy”. All images were evaluated using the algorithm of H. Kittler.
The analysis of available literature data indirectly confirms the role of development of skin tumors.
Literature review and clinical cases reports. Literature review. Clear cell acanthoma is also known as Degos acanthoma or acanthome à cellules claires. Clear cell acanthoma is a rare epithelial benign tumor with unknown etiology predominantly seen on the legs of adults, mostly those in their fifties or sixties. It has also been suggested that this lesion is an inflammatory psoriasiform dermatosis . Clear cell acanthoma has not been shown any gender, racial or ethnic preference. It is characterized by slow growth and may persist for years. The lesion is mostly solitary, most frequently found on the lower extremities of the middleaged adults and elderly individuals, sometimes a few lesions may be seen. Pinkbrown, slightly elevated, domeshaped papules or plaques may have peripheral scales and erosion on the surface . It is difficult to differentiate this lesion clinically from irritated seborrheic keratosis, Bowen disease, pyogenic granuloma, amelanotic melanoma, and basal cell carcinoma . Diagnosis is always based on histopathologic examination. Epidermis with psoriasiform acanthosis containing large, pale (clear) keratinocytes is the main histopathologic finding. A sharp demarcation from the surrounding epidermis is the rule [11, 20].
Pseudolymphomas of the skin are considered to be a group of benign reactive diseases sharing some common clinical and histopathologic features with cutaneous lymphomas. However, pseudolymphomas of the skin mostly demonstrate polyclonality with proliferation of both T and B lymphocytes. It is also possible that one lineage of a cell type may be predominant. Hence these pseudolymphomas are divided into B cell or T cell. Various entities with different etiologies and different clinical features, including actinic reticuloid, lymphomatoid contact dermatitis, and nodular scabies are described in the spectrum of pseudolymphoma with regard to their histopathologic features .
Lymphocytoma cutis is a Bcell pseudolymphoma presenting with erythematous papulonodular lesions. It is mostly idiopathic but may also develop following tick bites, injections, foreign body reactions, tattoos, or acupuncture . Pseudolymphomas triggered by these factors are also called the “reactive lymphoid hyperplasia” by some authors . Moreover, some systemic drugs may induce the development of pseudolymphoma, and this may be called “druginduced pseudolymphoma” [13, 15]. Borrelia burgdorferi infection may be a cause of lymphocytoma cutis in endemic areas . It is more common in children and young adults, but it may occur at any age. Women are more commonly affected. The nose, cheeks, forehead and earlobes are the most common locations of lymphocytoma cutis, but it may also be seen on the scalp, chest, nipple, arms and large skin folds. Generally, it appears as a solitary lesion, but in rare instances multiple, grouped, or generalized lesions may develop . Multiple lesions may be related to systemic drug use . Redbrown to redpurple, domeshaped, firm asymptomatic papules reach 0.5 to 2 cm size in a short time and then remain usually stable. Tiny papules with a tendency to confluence and plaques may be other presentations of pseudolymphoma. Some nodules may be lobulated. The surface of lymphocytoma cutis is usually intact .
Clinical differentiation from primary cutaneous lymphomas such as CD4+ small/medium pleomorphic Tcell lymphoma, and marginal zone lymphoma is difficult . Granuloma faciale, nonulcerated lesions of basal cell carcinoma, and keloid may also be considered in the differential diagnosis. In addition to basic histopathologic studies immunoprofile and molecular biological diagnostic procedures should be evaluated together to establish a correct diagnosis. Predominant lymphocytic nodular infiltration without atypia accompanied by plasma cells in the superficial dermis and intermingled eosinophils, and reactive germinal centers are the main histologic hallmarks . Infiltration sometimes invades the reticular dermis. As opposed to cutaneous lymphomas, monoclonality is absent, but staining with Bcell markers is predominant.
Descriptions of clinical cases. Two cases are discussed in the report. Both patients have solitary, well demarcated domeshape, pink papulouse lesion.
Patient N, male 53 y.o. The lesion located on inner side of right leg, upper third part. It was pink shiny, well demarcated ovalshaped solitary plaque 20 mm in diameter, with peripheral scales on the surface and stuck round edges. Patient found this lesion 2 years ago and it had little growth on the periphery. The lesion was unsuccessfully treated as psoriatic plaque (misdiagnosis) with topical steroids; he didn’t mention remission at all. This lesion was neither itchy nor painful. General condition was good, height 190.0 cm, body weight 97.0 kg. The structure of the body was correct. Skin was pale, regional lymph nodes were not palpable. Laboratory test results including complete blood cell count, urine analysis, and liver function test were within normal limits. We provided digital dermoscopy examination, which has shown that the most characteristic is the pattern of blood vessels. Linear pattern of vessels were observed on the periphery, on the central part, multiple dotted vessels arranged partly in linear, pearllike distribution and partly in reticular appearance. These dotted vessels, which represent the dilated capillaries, oriented mainly perpendicular to the skin surface in the elongated dermal papillae, formed a reticular appearance due to the regular distribution over the surface. Additionally, the multiple dotted vessels were circumscribed by a translucent collarette scaling (fig. 1). In pathology images, acanthotic epidermis containing larger than usual keratinocytes (~2x normal epidermal keratinocytes) are seen, well demarcated from adjacent epidermis. Also hypergranulosis, minimal nuclear pleomorphism, the vessels within the dermal papillae are dilated, tortuous and run vertically up the papillae (fig. 2).
The second case is presented by 37 year old female, who came to the outpatient clinic with main complaints of fast growing pink solitary lesion on the left eyebrow. General condition was satisfactory, consciousness was clear, gait was not broken. Height – 167.0 cm, body weight – 61.0 kg. During clinical examination, a lesion were found on the face. The lesion was presented by pink domeshaped papule, with sharply demarcated boarders on left eyebrow, located on the medial edge, size 7×7 mm (fig. 1, 2). Under dermatoscopy examination we observed homogenic structurless pink area, with reticular white lines, no chaos in pattern (fig. 3). Histology shows a nodular inflammatory infiltrate in the dermis. An infiltrate containing middle size, well formed lymphocytes with hyperchromic nuclear located mostly in the papillary and upper reticular dermis (topheavy) favors pseudolymphoma. The key histologic features favoring pseudolymphoma include the presence of a mixed infiltrate that includes histiocytes, eosinophils, and plasma cells, in addition to lymphocytes, no deep invasion, no prominent sclerosis was marked. Was prepared immunohistochemistry study with CD20, Ki67, CD3, CD5, CD43 was prepared. In the dermis, CD20 positive small B lymphocytes formating infiltration and containing in ~5 % Ki 67 positive germinal centers limited to the papillary and upper reticular dermis (topheavy) indicating pseudolymphoma, and a large number CD3, CD5, CD43 positive small sized T lymphocytes infiltration were found (fig. 4).
Conclusions. An overview of the modern literature and clinical presentations from our own practice suggests that clinically similar pink solitary skin lesions can be recognized by advanced dermoscopy examination. Der moscopic recognition of benign tumors may help to avoid unnecessary biopsies or surgical excision. Careful clinical and dermatoscopy monitoring gives additional ben efits for better recognition of skin tumors, but, of course in case of suspicious lesions special tests like histology from a skin biopsy, immunohistochemical stains and/or electron microscopy must be done. This kind of studies will be useful for better dermatoscopy description and make easier diagnostic of skin tumors.
- Potekaev NS, Sergeev YV. Skin Pseudolymphomas. Medical Аbstract Journal. 1978;11:13-19. (Russian).
- Ackerman AB, Breza TS, Capland L. Spongiotic simulants of mycosis fungoides. Arch Dermatol. 1974;109(2):218-219. https://doi.org/10.1001/archderm.1974.01630020034008
- Aguilar JL, Barcelo CM, Martin-Urda MT, Rodellas AC. Generalized cutaneous pseudolymphoma induced by neuroleptics. Arch Dermatol. 1992;128(1):121-123. https://doi.org/10.1001/archderm.1992.01680110135026
- Blum A, Metzler G, Bauer J, Rassner G, Garbe C. The dermatoscopic pattern of clear-cell acanthoma resembles psoriasis vulgaris. 2001;203:50-52. https://doi.org/10.1159/000051703
- Blumental G, Okun MR, Ponitch JA. Pseudolymphomatous reaction to tattoos. J Am Acad Dermatol. 1982;6(4 Pt 1):485-488. https://doi.org/10.1016/S0190-9622(82)70041-6
- Bocquet H, Bagot M, Roujeau JC. Drug-indced pseudolymphoma and drug hypersesivity syndrome (Drug Rash with Eosinophilia and Systemics Symptoms: DRESS). Semin Cutan Med Surg. 1996;15(4):250-257. https://doi.org/10.1016/S1085-5629(96)80038-1
- Can Baykal, Didem Yazganog K. Clinical Atlas of Skin Tumors. Springer, 2014. 499 p. https://doi.org/10.1007/978-3-642-40938-7
- Ecker RI, Winkelmann RK. Lymphomatoid contact dermatitis. Contact Dermat. 1981;7(2):84-93. https://doi.org/10.1111/j.1600-0536.1981.tb03985.x
- Figen Yazkan Akin,Ilgen Ertam, Can Ceylan, Alican Kazandi, Fezal Ozdemir. Clear cell acanthoma: New observations on dermatoscopy. Department of Dermatology, Ege University Medical Faculty. Bornova-Izmir, Turkey; 2008;74(3 issue):285-287. https://doi.org/10.4103/0378-6323.41396
- Gupta AK, Cooper KD, Ellis CN, Nickoloff BJ, Hanson CA, Brown MD et al. Lymphocytic infiltrates of the skin in association with cyclosporine therapy. J Am Acad Dermatol. 1990;23(6 Pt 1):1137-1141. https://doi.org/10.1016/0190-9622(90)70347-K
- Lyons G, Chamberlain AJ, Kelly JW. Dermoscopic features of clear cell acanthoma: five new cases and a review of existing published cases. Australas J Dermatol. 2015;56(3):206-211. https://doi.org/10.1111/ajd.12206
- Harris DW, Ostlere L, Buckley C, Whittaker S, Sweny P, Rustin MH. Phenytoin-induced pseudolymphoma. A report of a case and review of the literature. Br J Dermatol. 1992;127(4):403-406. https://doi.org/10.1111/j.1365-2133.1992.tb00463.x
- Kardaun SN, Scheffer E, Vermeer BJ. Drug-induced pseudolymphomatous skin reactions. Br J Dermatol. 1988;118(4):545-552. https://doi.org/10.1111/j.1365-2133.1988.tb02465.x
- Magro CM, Crowson PN. Drugs with antihistaminic properties as a cause of atypical cutaneous limphoid hyperplasia. J Аm Acad Dermatol. 1995;32(3):419-428. https://doi.org/10.1016/0190-9622(95)90063-2
- Sigal M, Pulic M. Pseudolymphomes medicamenteux a expression cutanee predominate. Ann Dermatol Venerol. 1993;120(2):175-180.
- Wall LM. Lymphomatoid contact dermatitis due to ethylenediamine dihydrochloride. Contact Dermatitis. 1982;8(1):51-54. https://doi.org/10.1111/j.1600-0536.1982.tb04135.x
- Charlesworth EN. Phenytoin-induced pseudolymphoma syndrome: an immunologic study. Arch Dermatol. 1977;113(4):477-480. https://doi.org/10.1001/archderm.1977.01640040085013
- Zalaudek I, Hofmann-Wellenhof R, Argenziano G. Dermoscopy of clear-cell acanthoma differs from dermoscopy of psoriasis. 2003;207(4):428-429. https://doi.org/10.1159/000074137
- Zalaudek I, Kreusch J, Giacomel J, Ferrara G, Catricalà C, Argenziano G. How to diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part I. Melanocytic skin tumors. J Am Acad Dermatol. 2010;63(3):361-374. https://doi.org/10.1016/j.jaad.2009.11.698
- Zalaudek I, Kreusch J, Giacomel J, Ferrara G, Catricalà C, Argenziano G. How to diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part II. Nonmelanocytic skin tumors. J Am Acad Dermatol. 2010;63(3):377-386. https://doi.org/10.1016/j.jaad.2009.11.697