Modern Concepts in Melanocytic Tumors. / Conceptos modernos en tumores melanocíticos.

The advent of molecular pathology has fueled unprecedented advances in the diagnosis and understanding of melanocytic tumors. These advances, however, have also generated concepts that may be difficult to grasp for clinical practitioners, who are not always conversant with the array of genetic techniques employed in the laboratory. These same practitioners, however, are being increasingly called on to provide treatments that are often based on the latest molecular findings for melanocytic tumors. We review the most recent concepts in the pathway classification of melanocytic tumors, including intermediate lesions known as melanocytomas. We examine the genetic and molecular techniques used to study these tumors, look at where they overlap, and discuss their limitations and some of the most difficult-to-interpret results.

[Translated article] Histopathologic and Trichoscopic Correlations in Nonscarring Alopecias.

Trichoscopy is an essential tool in the evaluation of alopecia. The current compilation of trichoscopic signs in this setting helps distinguish between different forms of hair loss and has improved our understanding of the pathogenic mechanisms involved. The trichoscopic signs are always linked to the pathogenic mechanisms of the alopecia being examined. We examine correlations between the main trichoscopic and histopathologic findings in nonscarring alopecias.

Vascular Malformations: A Histopathologic and Conceptual Appraisal.

In the field of vascular anomalies, distinguishing between vascular malformations and tumors has become crucial for a correct therapeutic approach. However, the differential diagnosis between these two groups is not always well explained in classical texts, mainly because many vascular malformations are still known with old names that suggest a tumoral nature. Also, genetic and pathogenic knowledge of these entities has greatly increased in recent decades, so researchers and clinicians now have a better understanding of vascular malformations. In this paper, we present the main histopathological tips to recognize and identify a vascular malformation as such. We also contextualize such information in the clinical and pathogenic knowledge for a better understanding of these entities.

Vascular Malformations: A Histopathologic and Conceptual Appraisal. / [Artículo traducido] Malformaciones vasculares: un enfoque histopatológico y conceptual.

In the field of vascular anomalies, distinguishing between vascular malformations and tumors has become crucial for a correct therapeutic approach. However, the differential diagnosis between these two groups is not always well explained in classical texts, mainly because many vascular malformations are still known with old names that suggest a tumoral nature. Also, genetic and pathogenic knowledge of these entities has greatly increased in recent decades, so researchers and clinicians now have a better understanding of vascular malformations. In this paper, we present the main histopathological tips to recognize and identify a vascular malformation as such. We also contextualize such information in the clinical and pathogenic knowledge for a better understanding of these entities.

Protocol for the Histologic Diagnosis of Cutaneous Melanoma: Consensus Statement of the Spanish Society of Pathology and the Spanish Academy of Dermatology and Venereology (AEDV) for the National Cutaneous Melanoma Registry. / Protocolo de diagnóstico histológico para muestras de pacientes con melanoma cutáneo. Documento de consenso de la SEAP y la AEDV para el Registro Nacional de Melanoma.

This article describes a proposed protocol for the histologic diagnosis of cutaneous melanoma developed for the National Cutaneous Melanoma Registry managed by the Spanish Academy of Dermatology and Venereology (AEDV). Following a review of the literature, 36 variables relating to primary tumors, sentinel lymph nodes, and lymph node dissection were evaluated using the modified Delphi method by a panel of 8 specialists (including 7 pathologists). Consensus was reached on the 30 variables that should be included in all pathology reports for cutaneous melanoma and submitted to the Melanoma Registry. This list can also serve as a model to guide routine reporting in pathology departments.

Granulomas in Dermatopathology: Principal Diagnoses - Part 1. / Granulomas en dermatopatología: principales entidades. Parte I.

This series of 2 articles on dermatopathologic diagnoses reviews conditions in which granulomas form. Part 1 clarifies concepts, discusses the presentation of different types of granulomas and giant cells, and considers a large variety of noninfectious diseases. Some granulomatous diseases have a metabolic origin, as in necrobiosis lipoidica. Others, such as granulomatous mycosis fungoides, are related to lymphomas. Still others, such as rosacea, are so common that dermatologists see them nearly daily in clinical practice.

Granulomas in Dermatopathology: Principal Diagnoses - Part 2. / Granulomas en dermatopatología: principales entidades. Parte II.

Part 2 of this series on granulomatous diseases focuses on skin biopsy findings. Whereas the first part treated noninfectious conditions (metabolic disorders and tumors, among other conditions), this part mainly deals with various types of infectious disease along with other conditions seen fairly often by clinical dermatologists.

Clinical and Histopathologic Characteristics of the Main Causes of Vascular Occusion - Part II: Coagulation Disorders, Emboli, and Other. / Dermatopatología de la oclusión intraluminal vascular: parteII (coagulopatías, émbolos y miscelánea).

Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. It also has a wide variety of causes, including thrombi, which we recently addressed in partI of this review. In this second part, we look at additional causes of vascular occlusion.

Clinical and Histopathologic Characteristics of the Main Causes of Vascular Occlusion - Part I: Thrombi. / Dermatopatología de la oclusión intraluminal vascular: parte I (trombos).

Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. The causes of vascular occlusion are also highly variable, ranging from thrombi triggered by the uncontrolled activation of coagulation mechanisms, on the one hand, to endothelial dysfunction or occlusion by material extrinsic to the coagulation system on the other. In a 2-part review, we look at the main causes of vascular occlusion and the key clinical and histopathologic findings. In this first part, we focus on vascular occlusion involving thrombi.

Cutaneous leiomyomas and leiomyosarcomas: an immunohistochemical study with p53.

BACKGROUND: Cutaneous smooth muscle tumors are rare and sometimes the differential diagnosis between leiomyoma and leiomyo-sarcoma is difficult and based in very subtle criteria. We therefore tried to investigate the use of p53 in such a conundrum. This marker has rarely been reported in cutaneous leiomyomas and even in more rare occasions, in cutaneous leiomyomas. MATERIAL AND METHODS: We studied 30 benign cutaneous smooth muscle tumors, including angioleiomyomas, common leiomyomas and a symplastic leiomyoma, as well as four leiomyosarcomas and one cutaneous metastasis of leiomyosarcoma. All cases were reviewed in order to confirm the diagnosis, before the cases were included in the study. In all cases, we performed an immunohistochemical study in all cases with p53 and the percentage of positive cells was estimate counting a total of 1000 cells per case. RESULTS: Six cases from the 31 (19.35%) benign cutaneous smooth muscle tumors showed some expression of p53. The expression of it varied from only occasional cells to 1% of the cells. On the contrary, all leiomyosarcomas investigated showed expression of p53, and in three of the four cases (75%), the marker was expressed by at least 80% of the tumoral cells. Only in one leiomyosarcoma, the marker was expressed by a low percentage (0.5%) of cells. No expression of p53 was found in the only case of symplastic leiomyoma, which was investigated. The case of a cutaneous metastasis of leiomyosarcoma showed expression of p53 by 20% of cells. CONCLUSIONS: We conclude that expression of p53 by a high percentage of cells in a cutaneous smooth muscle cell tumor should be considered as highly suspicious for malignancy.

Comparative study of Congo red fluorescence and immunohistochemistry in cutaneous amyloidosis.

BACKGROUND: Detection of amyloid can be done by several techniques either histochemical or immunohistochemical. Among them, one of the less mentioned in texts of reference and in reports on amyloidosis, is the examination with ultraviolet light of the stain of Congo red. We intend to examine cases of amyloidosis stained with Congo red with ultraviolet light and to see if such method offers advantages with respect to Congo red only and to immunohistochemistry. MATERIAL AND METHODS: We examined 12 cases of cutaneous amyloidosis Hematoxylin-Eosin, Congo red stains (with and without permanganate treatment), Thioflavin T and immunohistochemical stains. We also evaluated Congo red fluorescence (CRF). RESULTS: 66.66% were women and 33.34% were men. The traditional methods for the detection of amyloid (Congo red and Thioflavin T) were positive in 87.50% while immunohistochemistry was positive in 100% of the cases. In one case, immunohistochemistry detected Congo red negative deposits of amyloid. In another case, immunohistochemistry was strong while CRF was weak. CRF was always weak in all the cases in which it was seen. CONCLUSIONS: Immunohistochemistry is superior in the detection of cutaneous amyloid over the other techniques tested. CRF did not result, in our experience, to be so useful.

Mucin is not a rare finding in rosacea.

Mucin deposit is a feature that is not commonly mentioned in textbooks when talking about rosacea. Nevertheless, it is one of the prominent findings of a severe variant of the phymatous type of rosacea known as the fibrous type. We retrospectively investigated 20 cases of early stages of rosacea and examined the mucin deposit in them, with histochemical stains (Alcian Blue and Periodic Acid-Schiff). We found granulomas in 20% of these cases. Alcian Blue positive deposits of mucin were found in all cases with granulomas. The mucin was located in the granulomas (four cases) as well as in the infundibulum (one case). No deposits of mucin were evidenced in the dermis out of the granulomas, apart from the normal mucin of papillary and adventicial dermis. Periodic Acid-Schiff did not show any deposits in any case. Serologic lupus markers were negative in all patients with mucin deposits. We conclude that: (a) mucin is a common finding in granulomas of rosacea; (b) this mucin is probably not related to any progression to the mucinous variant of rhinophyma; (c) since discoid erythematosus lupus is a clinical differential of rosacea, it is important to be aware of the fact that mucin is a common finding in the granulomas, in order not to misdiagnose both entities.

Birefringent particles in granulomatous dermatitis, sarcoidal-type, as well as in other non-granulomatous skin disorders in patients without sarcoidosis.

Silica granuloma (SG) is a rare entity in literature. The relationship between SG and sarcoidosis has not always been clear. We tried to find out how common birefringent particles are in cutaneous biopsies from patients with and without sarcoidal granulomas. We studied the most recent 200 skin biopsies that came to our service. We also studied 10 cases of sarcoid-type granulomatous dermatitis. All of them were studied under the polarized light. Quantification of particles was classified from negative to very abundant. We found birefringent particles in 39.5% of the biopsies without a sarcoid-type granulomatous infiltrate. We found birefringent particles in 7 out of the 10 cases of the group with a sarcoid-type cutaneous dermatitis (70%). 5 of the 10 cases presented with systemic sarcoidosis, and from these, 4 presented with birefringent particles (80%). From the other 5 cases, we found birefringent particles in 3 cases (60%). Birefringent particles can be evidenced in the skin biopsy of patients with systemic sarcoidosis in a higher percentage than in non-granulomatous skin biopsies of subjects without a history of sarcoidosis. Therefore, evidence of those particles does not exclude sarcoidosis (Tab. 1, Fig. 4, Ref. 23).

Mammaglobin immunostaining in the differential diagnosis between cutaneous apocrine carcinoma and cutaneous metastasis from breast carcinoma.

The differential diagnosis between cutaneous apocrine carcinoma (CAC) and cutaneous metastases from breast carcinoma is commonly difficult. Many times, clinical information is crucial in the final diagnosis, because help that can be obtained from immunohistochemistry is usually limited concerning this subject. We used the antibody mammaglobin in order to study 10 cases of cutaneous metastasis of ductal breast carcinoma, and 2 cases of CAC. One of the CAC cases showed only scattered positive cells, while the other did not show any positivity. Four cases of metastatic breast carcinoma also showed scattered positive cells. In other five metastatic cases, positive cells were abundant, representing up to 60% of the tumoral cells. One case of metastatic breast carcinoma did not show any expression of mammaglobin at all. Although, more cases of CAC should probably be studied in the future before any categorical conclusion can be obtained, our results seem to indicate that a pattern of immunostaining with expression of mammaglobin in many cells would favor a metastatic origin of the tumor.

Irritated seborrheic keratosis with coarse keratohyalin granules.

AIMS: The viral etiology of certain types of seborrheic keratosis (SK) has been a controversial subject in literature, with different molecular results. On the contrary, to the molecular approach, some have suggested that certain types of SK are indeed warts, due to their morphologic features. We decided to investigate the presence of coarse keratohyalin granules in cases of irritated SK. MATERIAL, METHODS AND RESULTS: We examined the last 60 cases with such a diagnosis in our Service of Anatomic Pathology and found these granules in eight cases (7.5%). The granules were evidenced in squamous eddies in four cases, while they were seen in foci of hypergranulosis from the top part of the epidermis in five cases. These granules were evidenced in a few foci in three cases while they were seen in multiple foci in five cases. In these eight cases, we also looked for other morphologic signs suggesting a viral origin, such as papilated, exo-endophytic configuration, parakeratosis at the tips of digitations, dilated vessels in the papillae and koilocytes. While six cases presented at least any of these other features, in two of the eight cases (25%), the only clue suggesting a viral origin was the evidence of the thick granules of keratohyalin. CONCLUSIONS: We discuss the meaning of such a finding as described in literature, and conclude that it should be a specific feature to look out for, in cases of irritated SK, in order to exclude a diagnosis of verruca vulgaris.

Positive staining with Congo red in tissues with heat artifact due to cautery.

Congo red staining is rarely the source of false positives for amyloid. On the other hand, the heat artifact due to cautery in surgical specimens adopts some hyaline features, which can mimic amyloid deposits many times. Therefore, we decided to investigate the behavior of these artifacted areas with some of the ancillary techniques that are commonly used when diagnosing amyloidosis: Congo red staining (with and without treatment of the tissue by permanganate of potassium); Thioflavin T; polarized light and immunohistochemistry (for A amyloid, lambda chain and kappa chain). For that, 10 biopsies of different organs were selected with the condition that there was "evidence of heat artifact border". Our results showed that the artifacted border is strongly positive for Congo red (even after treatment with permanganate of potassium). It also showed apple-green birefringence when observed under polarized light. Nevertheless, it failed to express any of the markers investigated in the immunohistochemical study.