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Anais Brasileiros de Dermatologia

Print version ISSN 0365-0596On-line version ISSN 1806-4841

An. Bras. Dermatol. vol.84 no.4 Rio de Janeiro July/Aug. 2009 



Skin biopsy and its histopathologic analysis. Why? What for? How? Part I



Betina Werner

Specialist in Dermatopathology from the International Society of Dermatopathology. Master's degree in Surgical Clinic, concentration area in Surgical Pathology, from the Universidade Federal do Paraná. PhD in Child and Adolescent Health, concentration area in Dermatopathology, from the Universidade Federal do Paraná. Volunteer/invited lecturer/dermatopathologist at Services of Pathological Anatomy and Dermatology and Discipline of Pathological Anatomy, Universidade Federal do Paraná (UFPR) – Curitiba (PR), Brazil

Mailing Address




Histopathologic study is considered gold-standard for diagnosis of skin lesions, either neoplastic or inflammatory, most of the times. To take the most out of a skin biopsy, physicians should be aware of the reasons for performing the procedure followed by microscopic examination, the objectives to be achieved and the best manner to do the biopsy, including the best technique and best anatomical site for a particular disease.

Keywords: Biopsy; Microscopy; Skin; Skin/pathology




Different from what it may seem, skin biopsy with histopathologic study is a complex process. The peculiarity of this process is the number of variables involved to achieve its objective, that is, a correct and precise diagnosis. From the moment the dermatologist decides to perform a skin biopsy until receiving the microscopic analysis report, many factors can hinder the success of the procedure. The decision concerning the anatomical site and lesion where the specimen will be collected; choice of biopsy technique; identification, handling and fixation of the specimen; filling in the pathological order; macroscopic analysis of the skin specimen; histological processing and preparation of slides; microscopic study with diagnosis; and interpretation of the histopathologic report, are all very important steps that directly influence in the final result.

This article is divided into two parts. The first aims to discuss "why"skin biopsy should be done with histopathologic study and "what for", i.e., the reasons to perform the procedure. The first part also introduces "how"it should be carried out to obtain an adequate skin biopsy, discussing the importance of clinical information that should accompany the skin specimen sent for analysis. The second part is designed to further the "how", addressing the decision about technique and choice of most appropriate lesion or skin region for microscopic study of some specific diseases, besides dealing with some special situations, such as approach of melanocytic lesions and scalp.



According to an opinion of the Federal Medical Council, in 1995 (PC/CFM 44/95), "the pathological examination of specimens or parts removed from a human body should be performed by physicians acting with utmost care and using the best of their professional expertise, always to benefit patients and never as an obligation". 1 On the other hand, the Brazilian Society of Pathology, in the opinion 43/2006, stated that "the patient is the owner of his/her cells, tissues and organs, which cannot be simply discarded at the discretion of physicians. It is necessary to explain why tissues are excised, as well as to inform the objectives of a pathological procedure, and the patient consents or not about discarding his/her [remaining] material". 2 The same Society highlighted that "such decision must be documented using an Informed Consent, without which the assistant physician may be latter made accountable by the patient or relative, shall the outcome be unsatisfactory or unexpected".2 Independent of the opinion of the regulatory bodies, ultimately and most of the times it is the Dermatologist, Dermatologic Surgeon, Plastic Surgeon or other physician, specialist or not, who will decide by themselves what to do with the skin specimen removed from the patient. Different from inflammatory diseases, tumors and skin cysts are not always sent to pathologic study, depending on the certainty of the clinician or surgeon on it being a benign lesion. In a country as large as Brazil, the ability of physicians to make clinical diagnosis of skin lesions is heterogeneous, even among dermatologists, especially during the first years of their practical experience. In addition, two facts must be taken into account: the eyes of physicians may make mistakes judging a lesion as benign and incidental findings of neoplasm in benign lesions may occur.

On analyzing the cost/benefit ratio of sending the whole skin specimen for pathology, Lowy, Willis and Abrams 3 demonstrated a not significant increase in the number of lesions considered as "severe"by the authors when the group of general practitioners (GPs) studied began to send any and all skin specimens for histological analysis. The authors compared two periods - the first, in which 257 GPs selected material to send for pathologic examination; and the second, when the same physicians were oriented to send everything that was excised from the skin of their patients. Although the number of cases referred to pathology services raised by 29%, there was no statistically significant change in the number of malignant neoplasms sent for examination. Some articles showed an opinion different from these authors, speculating on diagnostic accuracy and reliability of conducting only macroscopic analysis of the lesion, at the risk of missing the diagnosis of malignant tumors. 4,5,6

Seborrheic keratoses, fibroepithelial polyps (acrochordons), epidermal cysts and "common"melanocytic nevi are some examples of skin lesions not always sent for pathological examination and discarded in the bin. Izikson et al. 7 reviewed 9204 pathological examinations in which the skin lesion has been clinically diagnosed as seborrheic keratosis and found 61 cases of melanoma. Due to clinical similarities between melanoma and pigmented seborrheic keratosis, these authors emphasized the need for microscopic exam of all seborrheic keratoses excised from patients. In another study, Cascajo, Reichel and Sanchez 8 found an association between seborrheic keratosis and basal cell carcinoma, Bowen's disease, keratoacanthoma and melanoma. Eads et al., 9 with the objective of analyzing the need to send seborrheic keratosis lesions to histopathologic study, reported the diagnosis of malignancy in 6.4% of cases. When considering acrochordons, there is a study suggesting no obligation to microscopically analyze these lesions 10. The authors observed five cases of malignancy among 1335 lesions studied with clinical suspicion of fibroepithelial polyp. 10 On the other hand, schwanoma 11 or eccrine nevus 12 are rarely clinically misdiagnosed as acrochordons. Epidermal cysts may also contain non-clinically diagnosed neoplasms, such as basal cell carcinoma 13,14 and epidermoid carcinoma.15 Finally, the usefulness of histologically assessing all lesions with clinical diagnosis of melanocytic nevi was discussed in an article by Reeck et al. 16 The authors mentioned the opinion of the American Academy of Dermatology, stating that "even experienced clinicians sometimes are not able to correctly diagnose pigmented lesions, based on only clinical criteria; therefore, when doubt remains, biopsy with pathologic examination are necessary". They reviewed 7734 pathological reports of a Dermopathology Service (received during a 40-day period, in 1995) and separated all cases in which the clinician or surgeon suspected of some type of nevus and made or not the differential diagnosis with melanoma. The authors found that 1.6% of lesions with no clinical suspicion of malignancy were diagnosed as melanoma. And 2.3% of lesions with clinical diagnosis of nevus and some comments, such as "atypical", "irritated", "that grew", etc, or when the physician asked for "malignancy to be excluded", were diagnosed as malignant neoplasm on histology, including 12 melanomas, 30 basal cell carcinomas and 3 epidermoid carcinomas. The researchers suggested that such study should be taken into account when considering whether biopsy with pathologic examination for melanocytic is mandatory or not.



The most traditional indication for skin biopsy with pathologic examination is diagnostic. 17 Inflammatory skin lesions with dubious clinical diagnosis and skin tumors or lesions that may be malignant need this study to define treatment and management. Another interesting use of the method is to confirm a well established clinical diagnosis. The histopathological examination often ratifies the dermatologist opinion to make therapeutic decisions. The psychological effect in patients (and, sometimes, in dermatologists) is also undeniable when the clinical diagnosis is ratified by the examination, especially when response to treatment chosen is not perfect. 17 The histopathologic report may be asked to authorize the use of some medications supplied by the National Unified Health System. And lastly, skin biopsy with histopathologic examination may be used for diagnostic records in the follow-up of patients for many years. Particularly in case of pigmented lesions that may recur, it may be difficult for the dermatologist to recall and prove in the future that the benign presumptive diagnosis and the choice of surgical technique were correct in the past. The histopathology order and report are formal documents and may be taken into court in favor of or against the physician. 17



The interdependence of clinic and pathology in diagnosis of skin diseases is unquestionable. Paraphrasing Miller, 18 skin biopsy transcends the mere technical act of removing a skin specimen from the patient. The author emphasizes the need of non-dermatologist physicians to be also trained in clinical differential diagnosis of skin lesions as well as in interpretation of histopathologic results. In other words, to perform the skin biopsy, the technical side of the procedure, is not the main issues when one is concerned with its practical use, that is, correct pathological diagnosis. 19 For this very reason, there is no question that dermatologists are the most skilled professionals to perform an adequate skin biopsy. Sellheyer and Bergfeld 20 compared the diagnostic accuracy of skin lesions between dermatologists and non-dermatologists. They concluded that dermatologists are twice more able to obtain correct clinical-pathological correlation. García-Solano et al. 21 demonstrated that histopathologic diagnoses made in skin specimens referred by a dermatology service are more specific (77%) than those obtained in biopsies referred by non-dermatological services (41%). This shows the direct importance of dermatologists in skin biopsy result. Choice of the technique and site of the biopsy, pertinent clinical information and presumptive diagnoses influenced the degree of accuracy of microscopic diagnosis, according to those authors. On the other hand, the experience of the pathologist who performs the microscopic analysis also influences the exactitude of the diagnosis of skin diseases. 21,22,23

Since the universe of diagnostic difficulties in dermatopathology is not the focus of the current article, we will now discuss the first part of "how"dermatologists can improve the pathological results obtained in a skin biopsy, beginning by filling in the order for the histopathological examination.

Clinical information. Every text on the relation skin lesion/histopathologic examination emphasizes the importance of clinical information to diagnostic conclusion. 17-25 Ideally, some data, such as sex and age, site and technique of the biopsy, duration of the disease and/or lesion that was biopsied, distribution and configuration of lesions, individual morphologic aspects of the lesions, symptoms, use of medication, presumptive diagnoses and/or differential diagnosis, should always be part of the pathological examination order. Actually, information is never too much, on the contrary, insufficient data may highly compromise interpreting pathological findings by the pathologist. In the specific case of inflammatory skin lesions, it is worth mentioning that they share histological features common to more than one disease. 17,19 Diseases clinically different as Grover disease and Darier disease, for instance, are identical under the microscope. Chart 1 shows three common histological patterns and the corresponding diseases that are part of each group. Basic clinical information can avoid the shame of a pathologist identifying lichen planus in the case of a benign lichenoid keratosis, for instance.



The histological diagnosis of a skin lesion is not considered definitive in very rare situations, and the histolopathological report is considered a medical and legal document. When physicians excise a skin specimen from a patient, they may or may not miss the chance of having the diagnosis established by a gold standard exam. Skin biopsy with histopathologic study may be indicated for any doubt in clinical judgment, be it diagnostic or therapeutic. The histopathologic report not only clarifies or confirms diagnosis and helps in clinical or surgical management, but it can also be a determinant factor in the medical-patient relationship, with psychological impact on both parties, enhancing the physician certainty about clinical diagnosis and the patient trust in the management.



1. Legislação. Pareceres do Conselho Federal de Medicina. [homepage]. [Acesso em 6 de abril de 2009]. Disponível em: pareceres/cfm/1995/44_1995.htm         [ Links ]

2. Pareceres da Sociedade Brasileira de Patologia. [homepage]. [Acesso em 6 de abril de 2009]. Disponível em pareceres.aspx?id=52         [ Links ]

3. Lowy A, Willis D, Abrams K. Is histological examination of tissue removed by general practitioners always necessary? Before and after comparison of detection rates of serious skin lesions. BMJ. 1997;315(7105):406-8         [ Links ]

4. Parslew R, Rhodes L. Is histological examination of tissue removed by GP's always necessary. Clinically important skin lesions would have been missed with a selective histological approach. BMJ. 1998; 316 (7133):778         [ Links ]

5. Cross P. Is histological examination of tissue removed by GPs always necessary? Even specialists get the clinical diagnosis wrong. BMJ. 1998;316(7133):778.         [ Links ]

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8. Cascajo CD, Reichel M, Sanchez JL. Malignant neoplasms associated with seborrheic keratoses. An analysis of 54 cases. Am J Dermatopathol. 1996;18:278-82         [ Links ]

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25. Boyd AS, Neldner KH. How to submit a specimen for cutaneous pathology analysis. Using the '5 D's' to get the most from biopsies. Arch Fam Med. 1997;6:64-6        [ Links ]



Mailing Address:
Betina Werner
Rua. Dr. Nelson de Souza Pinto, 759
CEP: 82200-060 - Curitiba, PR.
Tel./Fax: 41 3232 1906 41 3232 3524



Conflict of interest: None
Financial funding: None
How to cite this article: Werner B. Biópsia de pele e seu estudo histológico. Por quê? Para quê? Como? Parte I. An Bras Dermatol. 2009;84(4)

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