Ricardo Macarenco - Academia.edu (original) (raw)

Papers by Ricardo Macarenco

Anais Brasileiros de Dermatologia, 2016

The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and tr... more The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In this second part, the following clinical questions were answered: 1) which patients with primary cutaneous melanoma benefit from sentinel lymph node biopsy? 2) Follow-up with body mapping is indicated for which patients? 3) Is preventive excision of acral nevi beneficious to patients? 4) Is preventive excision of giant congenital nevi beneficious to patients? 5) How should stages 0 and I primary cutaneous melanoma patients be followed?

Anais brasileiros de dermatologia, 2015

The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and tr... more The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In the first part, the following clinical questions were answered: 1) The use of dermoscopy for diagnosis of primary cutaneous melanoma brings benefits for patients when compared with clinical examination? 2) Does dermoscopy favor diagnosis of nail apparatus melanoma? 3) Is there a prognostic difference when incisional or excisional biopsies are used? 4) Does revision by a pathologist trained in melanoma contribute...

Surgical and Experimental Pathology, 2019

Despite the immunotherapeutics and target therapy agents, the survival of patients with advanced ... more Despite the immunotherapeutics and target therapy agents, the survival of patients with advanced melanoma is still low. Notch signaling is able to regulate many aspects of melanomagenesis. Comparative analyses of common melanocytic nevi, dysplastic nevi and melanomas demonstrated increased expression of Notch1, Notch2 and their ligands, indicating that a positive regulation of these components may be related to the progression of melanoma. Some strategies such as gamma-secretase inhibitors (GSI) have been explored in patients with refractory metastatic disease or locally advanced disease of solid tumors. Two major classes of Notch inhibitors are currently in clinical development: GSI and monoclonal antibodies against Notch receptors or their ligands. Inhibition of Notch by GSI has been shown to decrease melanoma growth. GSI RO4929097 co-administered with cisplatin, vinblastine and temozolomide promotes greater elimination of tumor cells. The Notch pathway needs to be explored in the...

The American Journal of Dermatopathology, 2009

Myositis ossificans is a benign pseudosarcomatous bone-forming lesion, histologically characteriz... more Myositis ossificans is a benign pseudosarcomatous bone-forming lesion, histologically characterized by 2 components: a spindle (myo)fibroblastic cell population and a bony component that is arranged in a "zonal" pattern. It mainly affects the deep soft tissues of limbs, but its occurrence in other unusual locations, such as abdomen, inside nerves, and the subcutaneous fat, has been reported. The existence of myositis ossificans restricted to the skin has rarely been published under the term "fibro-osseous lesion of the external auditory canal." Here, we describe an additional case in the external auditory canal, emphasizing its differential diagnosis and alerting dermatopathologists and pathologists to the possibility of encountering such lesion in this anatomic location. For purposes of unifying terms, we propose that cases similar to ours be called "cutaneous myositis ossificans" instead of fibro-osseous lesion of the external auditory canal.

The American Journal of Dermatopathology, 2009

Fox-Fordyce disease is a condition with protean histopathological alterations whose pathogenesis ... more Fox-Fordyce disease is a condition with protean histopathological alterations whose pathogenesis remains a mystery. Although recent studies have addressed histological changes specific of this disease, including perifollicular xanthomatosis, no attention has been given to apocrine acini dilation as an adjunct histopathological finding to the diagnosis. Moreover, although previous efforts were done to demonstrate that perifollicular foamy histiocytes harbor apocrine secretion content, this concept has not been proved to date. In this study, we report 2 cases harboring prominent dilation of apocrine coils with mucinous content. Such mucinous content showed mucin profile identical to the dermal mucin deposits in both cases. Of note, perifollicular foamy histiocytes demonstrated cytoplasmic mucin, supporting the suggestion that these cells phagocytose apocrine secretion. Although not specific, apocrine coil dilation is another histopathological feature of Fox-Fordyce disease and it may be used as a low-power magnification clue for the correct diagnosis. We also propose that the so-called perifollicular xanthomatosis may be composed of muciphages or mixed cell (muciphages/xanthomatous) population, an issue that should be further investigated in future studies.

The American Journal of Dermatopathology, 2013

Recently, 2 putatively novel clinicopathological entities, macular arteritis (MA) and lymphocytic... more Recently, 2 putatively novel clinicopathological entities, macular arteritis (MA) and lymphocytic thrombophilic arteritis (LTA), have been described. Both exhibit an indolent chronic course and erythematous and hyperpigmented macules (MA > LTA) and papules/plaques (LTA > MA), often in a reticulated pattern on the lower limbs. Histopathologically, they show varying degrees of lymphocyte infiltration and disruption of the arterial wall, concentric luminal fibrin deposition, and in some cases, fibrointimal scarring (endarteritis obliterans). This spectrum of histology overlaps with the subacute, reparative, and healed stages reported for cutaneous polyarteritis nodosa (CPAN). Herein, we report 2 cases of cutaneous lymphocytic arteritis, 1 with persistent indolent disease and the second with acute self-limited disease. Comparing these 2 patients' findings with that reported for MA, LTA, and CPAN highlights a clinicopathologic spectrum, which exhibits increasing disease severity moving from MA to LTA to CPAN to systemic polyarteritis nodosa. Given the clinicopathologic similarities, we conclude that our cases and cases previously reported as MA or LTA likely represent an indolent form of CPAN.

Journal of Oral Pathology and Medicine, 2006

Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm that usually arises in the pleur... more Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm that usually arises in the pleura. Although this tumor has been described in other sites, including the head and neck area, in the oropharynx it is extremely rare. We report the first case of a SFT arising from the palatine tonsil of a 62-year-old man. The tumor consisted of spindle-shaped cells distributed in a haphazard pattern and presented atypical histological features such as hypercellular areas and high mitotic count. Immunohistochemical studies showed strong positivity for CD34 and bcl-2, and weak positivity for desmin. Smooth muscle actin, S-100 protein and cytokeratines were negative. The patient was well without disease 1 year after surgery.

International Journal of Gynecological Cancer, 2006

Silva-Filho AL, Traiman P, Triginelli SA, Reis FM, Pedrosa MS, Miranda D, Abreu ES, Macarenco R, ... more Silva-Filho AL, Traiman P, Triginelli SA, Reis FM, Pedrosa MS, Miranda D, Abreu ES, Macarenco R, Cunha-Melo JR. Association between CD31 expression and histopathologic features in stage IB squamous cell carcinoma of the cervix. Int J Gynecol Cancer 2006;16:757-762.

Cancer Genetics and Cytogenetics, 2007

Cancer Genetics and Cytogenetics, 2006

Dedifferentiated liposarcoma, a subtype of liposarcoma, is characterized by juxtaposition of well... more Dedifferentiated liposarcoma, a subtype of liposarcoma, is characterized by juxtaposition of well-differentiated liposarcoma with a nonadipocytic sarcoma. A peculiar form of dedifferentiated liposarcoma has been described, characterized by a nonlipogenic component with a neural-like whorling pattern of growth and metaplastic bone formation. We report the cytogenetic and molecular genetic findings of this peculiar form of dedifferentiation in a retroperitoneal tumor found in a 58-year-old woman. The neoplasm had the typical histologic findings and a complex karyotype characterized by several numeric and structural chromosome abnormalities, including the presence of ring and giant rod chromosomes. Molecular genetic studies found high levels of amplification of the MDM2 oncogene, consistent with the amplification of the 12q14 chromosome band, a cytogenetic abnormality commonly found in these tumors. These findings indicate that, despite its unique and peculiar morphologic features, this unusual type of dedifferentiated liposarcoma shares many of the cytogenetic and molecular genetic abnormalities found in other forms of dedifferentiation. However, the specific cytogenetic and molecular determinants of these peculiar morphologic findings remain unknown.

Genes, Chromosomes and Cancer, 2008

Giant cell fibroblastoma (GCF) is a subcutaneous mesenchymal neoplasm characterized by the chromo... more Giant cell fibroblastoma (GCF) is a subcutaneous mesenchymal neoplasm characterized by the chromosomal t(17;22), which results in the formation of the fusion gene COL1A1-PDGFB. This same fusion gene is also seen in the supernumerary ring chromosome of dermatofibrosarcoma protuberans (DFSP). Several studies have addressed the molecular genetics of DFSP but molecular cytogenetic characterization of individual areas and cell components in pure GCF and GCF/DFSP hybrids have not been performed. Herein, we studied the frequency and genomic copy number of COL1A1-PDGFB in pure GCF and GCF/ DFSP hybrids, and identified the molecular cytogenetic signatures in individual cells in each component. Four pure GCF and nine GCF/DFSP hybrids were studied. All tumors exhibited classical histological features and CD34 expression. COL1A1 and PDGFB rearrangements were evaluated by fluorescence in situ hybridization (FISH) using probes for COL1A1 and PDGFB on paraffin-embedded thin tissue sections. All GCF and GCF/DFSP hybrids showed unbalanced rearrangements of COL1A1-PDGFB at the molecular cytogenetic level. Genomic gains of COL1A1-PDGFB were found predominantly in the DFSP component of GCF/DFSP hybrids but in none of the pure GCF, suggesting that these gains are associated with the histologic evolution of GCF into DFSP. The molecular cytogenetic abnormalities were found not only in the spindle/stellated cells but also in individual nuclei of the multinucleated giant cells, suggesting that these cells may result from the fusion of individual neoplastic cells. V V C 2007 Wiley-Liss, Inc.

Modern Pathology, 2008

Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, the two most common being... more Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, the two most common being adenoid cystic carcinoma and mucoepidermoid carcinoma. Although they usually have an indolent behavior, adenoid cystic carcinomas can be more aggressive, with 5-year survival as low as 55%. Unfortunately, these tumors do not respond well to chemotherapy. In contrast to the most common subtypes of lung carcinomas, epidermal growth factor receptor studies have not been carried out in this group of tumors. Herein we report a series of 24 cases (12 adenoid cystic and 12 mucoepidermoid carcinomas) tested for epidermal growth factor receptor protein expression, epidermal growth factor receptor gene copy gains, and epidermal growth factor receptor gene mutational status, through immunohistochemistry, fluorescence in situ hybridization, and sequencing of the exons 18-21, respectively. Overall, 91 and 92% of the adenoid cystic carcinomas and mucoepidermoid carcinomas expressed epidermal growth factor receptor protein. Chromosome 7 polysomy occurred in 25% of the cases (four adenoid cystic carcinomas and two mucoepidermoid carcinomas). No epidermal growth factor receptor gene amplification was detected and no mutation was found in exons 18-21 of the epidermal growth factor receptor gene. Immunoexpression of epidermal growth factor receptor in salivary gland-type lung carcinomas is not related to epidermal growth factor receptor gene copy number or mutational status.

Anais Brasileiros de Dermatologia, 2016

The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and tr... more The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In this second part, the following clinical questions were answered: 1) which patients with primary cutaneous melanoma benefit from sentinel lymph node biopsy? 2) Follow-up with body mapping is indicated for which patients? 3) Is preventive excision of acral nevi beneficious to patients? 4) Is preventive excision of giant congenital nevi beneficious to patients? 5) How should stages 0 and I primary cutaneous melanoma patients be followed?

Anais brasileiros de dermatologia, 2015

The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and tr... more The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In the first part, the following clinical questions were answered: 1) The use of dermoscopy for diagnosis of primary cutaneous melanoma brings benefits for patients when compared with clinical examination? 2) Does dermoscopy favor diagnosis of nail apparatus melanoma? 3) Is there a prognostic difference when incisional or excisional biopsies are used? 4) Does revision by a pathologist trained in melanoma contribute...

Surgical and Experimental Pathology, 2019

Despite the immunotherapeutics and target therapy agents, the survival of patients with advanced ... more Despite the immunotherapeutics and target therapy agents, the survival of patients with advanced melanoma is still low. Notch signaling is able to regulate many aspects of melanomagenesis. Comparative analyses of common melanocytic nevi, dysplastic nevi and melanomas demonstrated increased expression of Notch1, Notch2 and their ligands, indicating that a positive regulation of these components may be related to the progression of melanoma. Some strategies such as gamma-secretase inhibitors (GSI) have been explored in patients with refractory metastatic disease or locally advanced disease of solid tumors. Two major classes of Notch inhibitors are currently in clinical development: GSI and monoclonal antibodies against Notch receptors or their ligands. Inhibition of Notch by GSI has been shown to decrease melanoma growth. GSI RO4929097 co-administered with cisplatin, vinblastine and temozolomide promotes greater elimination of tumor cells. The Notch pathway needs to be explored in the...

The American Journal of Dermatopathology, 2009

Myositis ossificans is a benign pseudosarcomatous bone-forming lesion, histologically characteriz... more Myositis ossificans is a benign pseudosarcomatous bone-forming lesion, histologically characterized by 2 components: a spindle (myo)fibroblastic cell population and a bony component that is arranged in a "zonal" pattern. It mainly affects the deep soft tissues of limbs, but its occurrence in other unusual locations, such as abdomen, inside nerves, and the subcutaneous fat, has been reported. The existence of myositis ossificans restricted to the skin has rarely been published under the term "fibro-osseous lesion of the external auditory canal." Here, we describe an additional case in the external auditory canal, emphasizing its differential diagnosis and alerting dermatopathologists and pathologists to the possibility of encountering such lesion in this anatomic location. For purposes of unifying terms, we propose that cases similar to ours be called "cutaneous myositis ossificans" instead of fibro-osseous lesion of the external auditory canal.

The American Journal of Dermatopathology, 2009

Fox-Fordyce disease is a condition with protean histopathological alterations whose pathogenesis ... more Fox-Fordyce disease is a condition with protean histopathological alterations whose pathogenesis remains a mystery. Although recent studies have addressed histological changes specific of this disease, including perifollicular xanthomatosis, no attention has been given to apocrine acini dilation as an adjunct histopathological finding to the diagnosis. Moreover, although previous efforts were done to demonstrate that perifollicular foamy histiocytes harbor apocrine secretion content, this concept has not been proved to date. In this study, we report 2 cases harboring prominent dilation of apocrine coils with mucinous content. Such mucinous content showed mucin profile identical to the dermal mucin deposits in both cases. Of note, perifollicular foamy histiocytes demonstrated cytoplasmic mucin, supporting the suggestion that these cells phagocytose apocrine secretion. Although not specific, apocrine coil dilation is another histopathological feature of Fox-Fordyce disease and it may be used as a low-power magnification clue for the correct diagnosis. We also propose that the so-called perifollicular xanthomatosis may be composed of muciphages or mixed cell (muciphages/xanthomatous) population, an issue that should be further investigated in future studies.

The American Journal of Dermatopathology, 2013

Recently, 2 putatively novel clinicopathological entities, macular arteritis (MA) and lymphocytic... more Recently, 2 putatively novel clinicopathological entities, macular arteritis (MA) and lymphocytic thrombophilic arteritis (LTA), have been described. Both exhibit an indolent chronic course and erythematous and hyperpigmented macules (MA > LTA) and papules/plaques (LTA > MA), often in a reticulated pattern on the lower limbs. Histopathologically, they show varying degrees of lymphocyte infiltration and disruption of the arterial wall, concentric luminal fibrin deposition, and in some cases, fibrointimal scarring (endarteritis obliterans). This spectrum of histology overlaps with the subacute, reparative, and healed stages reported for cutaneous polyarteritis nodosa (CPAN). Herein, we report 2 cases of cutaneous lymphocytic arteritis, 1 with persistent indolent disease and the second with acute self-limited disease. Comparing these 2 patients' findings with that reported for MA, LTA, and CPAN highlights a clinicopathologic spectrum, which exhibits increasing disease severity moving from MA to LTA to CPAN to systemic polyarteritis nodosa. Given the clinicopathologic similarities, we conclude that our cases and cases previously reported as MA or LTA likely represent an indolent form of CPAN.

Journal of Oral Pathology and Medicine, 2006

Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm that usually arises in the pleur... more Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm that usually arises in the pleura. Although this tumor has been described in other sites, including the head and neck area, in the oropharynx it is extremely rare. We report the first case of a SFT arising from the palatine tonsil of a 62-year-old man. The tumor consisted of spindle-shaped cells distributed in a haphazard pattern and presented atypical histological features such as hypercellular areas and high mitotic count. Immunohistochemical studies showed strong positivity for CD34 and bcl-2, and weak positivity for desmin. Smooth muscle actin, S-100 protein and cytokeratines were negative. The patient was well without disease 1 year after surgery.

International Journal of Gynecological Cancer, 2006

Silva-Filho AL, Traiman P, Triginelli SA, Reis FM, Pedrosa MS, Miranda D, Abreu ES, Macarenco R, ... more Silva-Filho AL, Traiman P, Triginelli SA, Reis FM, Pedrosa MS, Miranda D, Abreu ES, Macarenco R, Cunha-Melo JR. Association between CD31 expression and histopathologic features in stage IB squamous cell carcinoma of the cervix. Int J Gynecol Cancer 2006;16:757-762.

Cancer Genetics and Cytogenetics, 2007

Cancer Genetics and Cytogenetics, 2006

Dedifferentiated liposarcoma, a subtype of liposarcoma, is characterized by juxtaposition of well... more Dedifferentiated liposarcoma, a subtype of liposarcoma, is characterized by juxtaposition of well-differentiated liposarcoma with a nonadipocytic sarcoma. A peculiar form of dedifferentiated liposarcoma has been described, characterized by a nonlipogenic component with a neural-like whorling pattern of growth and metaplastic bone formation. We report the cytogenetic and molecular genetic findings of this peculiar form of dedifferentiation in a retroperitoneal tumor found in a 58-year-old woman. The neoplasm had the typical histologic findings and a complex karyotype characterized by several numeric and structural chromosome abnormalities, including the presence of ring and giant rod chromosomes. Molecular genetic studies found high levels of amplification of the MDM2 oncogene, consistent with the amplification of the 12q14 chromosome band, a cytogenetic abnormality commonly found in these tumors. These findings indicate that, despite its unique and peculiar morphologic features, this unusual type of dedifferentiated liposarcoma shares many of the cytogenetic and molecular genetic abnormalities found in other forms of dedifferentiation. However, the specific cytogenetic and molecular determinants of these peculiar morphologic findings remain unknown.

Genes, Chromosomes and Cancer, 2008

Giant cell fibroblastoma (GCF) is a subcutaneous mesenchymal neoplasm characterized by the chromo... more Giant cell fibroblastoma (GCF) is a subcutaneous mesenchymal neoplasm characterized by the chromosomal t(17;22), which results in the formation of the fusion gene COL1A1-PDGFB. This same fusion gene is also seen in the supernumerary ring chromosome of dermatofibrosarcoma protuberans (DFSP). Several studies have addressed the molecular genetics of DFSP but molecular cytogenetic characterization of individual areas and cell components in pure GCF and GCF/DFSP hybrids have not been performed. Herein, we studied the frequency and genomic copy number of COL1A1-PDGFB in pure GCF and GCF/ DFSP hybrids, and identified the molecular cytogenetic signatures in individual cells in each component. Four pure GCF and nine GCF/DFSP hybrids were studied. All tumors exhibited classical histological features and CD34 expression. COL1A1 and PDGFB rearrangements were evaluated by fluorescence in situ hybridization (FISH) using probes for COL1A1 and PDGFB on paraffin-embedded thin tissue sections. All GCF and GCF/DFSP hybrids showed unbalanced rearrangements of COL1A1-PDGFB at the molecular cytogenetic level. Genomic gains of COL1A1-PDGFB were found predominantly in the DFSP component of GCF/DFSP hybrids but in none of the pure GCF, suggesting that these gains are associated with the histologic evolution of GCF into DFSP. The molecular cytogenetic abnormalities were found not only in the spindle/stellated cells but also in individual nuclei of the multinucleated giant cells, suggesting that these cells may result from the fusion of individual neoplastic cells. V V C 2007 Wiley-Liss, Inc.

Modern Pathology, 2008

Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, the two most common being... more Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, the two most common being adenoid cystic carcinoma and mucoepidermoid carcinoma. Although they usually have an indolent behavior, adenoid cystic carcinomas can be more aggressive, with 5-year survival as low as 55%. Unfortunately, these tumors do not respond well to chemotherapy. In contrast to the most common subtypes of lung carcinomas, epidermal growth factor receptor studies have not been carried out in this group of tumors. Herein we report a series of 24 cases (12 adenoid cystic and 12 mucoepidermoid carcinomas) tested for epidermal growth factor receptor protein expression, epidermal growth factor receptor gene copy gains, and epidermal growth factor receptor gene mutational status, through immunohistochemistry, fluorescence in situ hybridization, and sequencing of the exons 18-21, respectively. Overall, 91 and 92% of the adenoid cystic carcinomas and mucoepidermoid carcinomas expressed epidermal growth factor receptor protein. Chromosome 7 polysomy occurred in 25% of the cases (four adenoid cystic carcinomas and two mucoepidermoid carcinomas). No epidermal growth factor receptor gene amplification was detected and no mutation was found in exons 18-21 of the epidermal growth factor receptor gene. Immunoexpression of epidermal growth factor receptor in salivary gland-type lung carcinomas is not related to epidermal growth factor receptor gene copy number or mutational status.