An Immunohistochemical Study of Breast Cancer Brain Metastases: The Role of CD44 and AKT in the Prognosis.

Breast cancer is a major health burden, and up to one-third of patients with breast cancer develop brain metastases, which are linked to a very poor prognosis. Few biomarkers are available to predict the prognosis of patients with metastases. Assessment by immunohistochemistry may be used as a tool to predict the behavior of these tumors. A retrospective transversal study including 114 patients (diagnosed between 2000 and 2016) with breast cancer brain metastases was carried out using archival biological material from 114 patients with breast cancer brain metastases. Expression of CD44, HER2, ER, PR, CA9, PDL-1, CD133, ALDH1, PTEN, AKT, PI3K, and AR markers was assessed by immunohistochemistry. The overexpression of CD44 and AKT was associated with worse overall survival ( P =0.047 and P =0,034, respectively), on univariate analysis, in the cohort of parenchymal and bone metastases; the impact of AKT expression was also evident in the parenchymal cohort on uni ( P =0.021) and multivariate analysis ( P =0.027). The remaining markers did not exhibit a statistical correlation. Immunohistochemistry markers such as CD44 and AKT may have a prognostic impact on survival in patients with breast cancer brain metastases. The conjugation with other markers may help with the stratification of patients and therapy.

Digital pathology implementation in a private laboratory: The CEDAP experience.

Introduction: The transition to digital pathology has been carried out by several laboratories across the globe, with some cases described in Portugal. In this article, we describe the transition to digital pathology in a high-volume private laboratory, considering the main challenges and opportunities. Material and methods: Our process started in 2020, with laboratory workflow adaptation and we are currently using a high-capacity scanner (Aperio GT450DX) to digitize slides at 20×. The visualization system, Aperio eSlide Manager WebViewer, is integrated into the Laboratory System. The validation process followed the Royal College of Pathologists Guidelines. Results: Regarding validation, the first phase detected an error rate of 6.8%, mostly due to digitization errors. Phase optimization and collaboration with technical services led to improvements in this process. In the second validation phase, most of the slides had the desired quality for evaluation, with only an error rate of 0.6%, corrected with a new scan. The interpathologist correlation had a total agreement rate of 96.87% and 3.13% partial agreement. Conclusion: The implementation and validation of digital pathology was a success, being ready for prime time. The total integration of all laboratory systems and the acquisition of new equipment will maximize their use, especially with the application of artificial intelligence algorithms.

Clinical and Pathological Features of Double-Hit and Triple-Hit High-Grade B-Cell Lymphomas: A Retrospective Study from Three Portuguese Tertiary Centers.

Background: High-grade B-cell lymphoma (HGBL) with rearrangements of MYC and BCL2 and/or BCL6, called double and triple-hit lymphomas (DTH-HGBL), are lymphoid malignancies with inferior outcomes when treated with standard chemotherapy. The identification of DTH-HGBL cases is challenging, considering their variable clinical, morphologic, and immunohistochemical features. Materials and Methods: Retrospective revision of medical data of patients diagnosed with DTH-HGBL confirmed by FISH, between January 2010 and January 2020, in three Tertiary Portuguese Hospitals (Coimbra Hospital and University Center, Portuguese Oncology Institute - Coimbra and Portuguese Oncology Institute - Porto). Pathological features, morphology, and immunohistochemical profile were evaluated by at least two experienced pathologists in hematopoietic and lymphoid neoplasms. Results: The cohort included 24 patients: 33.3% triple-hit, 58.3%, MYC/BCL2 double-hit and 8.3% MYC/BCL6 double-hit. There was no gender predominance, with a median age of 62.5±14.3y, 33.3% were diagnosed as nodal disease, and 66.7% as extranodal. Morphologic features of DLBCL were present in 50% of cases, morphological features of both DLBCL and Burkitt lymphoma (DLBCL/BL) in 45.8% and 4.2% of blastoid morphology. Immunohistochemical evaluation, regarding the Hans algorithm, revealed a Germinal center (GC)/GC-like subtype in 83.3% of cases and a non-GC/non-GC-like subtype in 16.7%.  MYC was positive in 42.9% and the median proliferative index was 80±12.4%. Conclusion: DTH-HGBL has a very broad range of features. We consider that a cost-effective approach would be to perform cytogenetic analysis in DLBCL and DLBCL/BL cases with GC/GC-like subtype. MYC and BCL2 immunohistochemistry can be useful to identify patients who may benefit from more aggressive therapies, but not as tools for case selection for FISH.

Sebaceous Carcinoma of the Vulva: An Unexpected Diagnosis and Literature Review.

Sebaceous carcinoma of the vulva is a rare malignancy of the sebaceous glands, with potentially aggressive behaviour, that is usually found in the peri-ocular area. Nonetheless, there are sebaceous glands in the vulva and this diagnosis is especially rare, with only ten cases described in the literature. We report a case of 78-year-old female patient who presented with vulvar pruritus, previously treated with topical steroid and antifungal treatments, without improvement. The vulvar examination showed a visible yellow papule, 12 x 10 mm on the right major labia, which was biopsied and the microscopic examination revealed an invasive sebaceous carcinoma of the vulva, with an in situ component. We performed an uneventful excisional biopsy, followed by a subsequent margin widening. Three months after the diagnosis, she presented with the first recurrence. Two and half years after the diagnosis, she recurred with a larger lesion (13 mm) in the upper half of small right lip, more than 10 mm away from the midline. In a multidisciplinary meeting it was decided that the patient should undergo partial right vulvectomy with homolateral inguino-femoral sentinel node biopsy (one negative node). There was no evidence of recurrence one-year post-surgery.

O carcinoma sebáceo da vulva é uma neoplasia maligna rara das glândulas sebáceas com comportamento potencialmente agressivo, mais comummente encontrada na área periocular. Este diagnóstico é particularmente raro nas glândulas sebáceas da vulva, com apenas dez casos previamente descritos na literatura. Relatamos o caso de uma paciente de 78 anos que se apresentou com prurido vulvar, anteriormente tratado com corticóides tópicos e antifúngicos, sem melhoria evidente. Ao exame objetivo apresentava uma pápula amarela visível, com cerca de 12 x 10 mm no grande lábio direito, que foi biopsada. O exame microscópico revelou um carcinoma sebáceo invasivo da vulva, com componente in situ. Posteriormente, foi realizada uma biópsia excisional, com alargamento de margens, sem intercorrências. Três meses após o diagnóstico, surgiu a primeira recidiva, pelo que foi realizada uma nova biópsia excisional. Dois anos e meio após o diagnóstico, a doente apresentava uma lesão com 13 mm, na metade superior do pequeno lábio direito, mais de 10 mm afastada da linha mediana. Em reunião multidisciplinar decidiu-se que deveria ser submetida a uma vulvectomia parcial direita, com pesquisa de gânglio sentinela inguino-femoral homolateral (um gânglio negativo). Um ano após a cirurgia, a doente encontra-se sem evidência de recorrência.

When the uterine mass is not a leiomyoma.

A 37-year-old nulliparous woman with abnormal uterine bleeding and a uterine mass suggestive of a leiomyoma not responding to medical therapy was submitted to two hysteroscopies with histological analysis. The first one showed a 'leiomyoma' and the second a 'uterine smooth muscle tumour of uncertain malignant potential/epithelioid leiomyosarcoma, with positivity for hormonal receptors'. The patient was submitted to a total hysterectomy with bilateral salpingo-oophorectomy, and the microscopic examination of the tumour revealed a 'uterine tumour resembling ovarian sex-cord tumours'. According to the literature, most cases are diagnosed in postmenopausal women and have a favourable prognosis. These rare tumours have uncertain malignant potential and have no established treatment protocol, but it appears that a fertility-sparing approach is possible once they are well diagnosed.

Myeloid sarcoma of the small intestine in a patient without overt acute myeloid leukaemia: a challenging diagnosis of a rare condition.

Myeloid sarcoma (MS) is a rare condition that most commonly occurs in the setting of acute myeloidleukaemia (AML) or other chronic myeloproliferative disorders. It presents as an abnormal growth that can develop anywhere in the human body, and its clinical manifestations are often non-specific.We present the case of a patient admitted to the emergency room with bowel obstruction. After careful clinical assessment, she underwent a right hemicolectomy. After a thorough examination of the surgical pathology specimen, including testing a wide array of immunohistochemical markers, the patient was timely diagnosed with MS, allowing for the implementation of the appropriate treatment to achieve complete remission. This is crucial, since non-leukaemic patients with untreated MS always progress to AML, and have a better prognosis if adequate therapy is implemented early. Our patient is now in the second postoperative year and shows no signs of relapse.

Invasive bladder urothelial carcinoma, plasmacytoid variant: case report / Carcinoma urotelial invasor de bexiga, variante plasmocitoide: relato de caso

ABSTRACT Invasive bladder urothelial carcinoma, plasmacytoid variant is a rare entity with scarce cases reported in the literature. We report a case of a 79 years old male, subjected to transurethral resection of bladder tumor, which histological examination revealed a pT1 high-grade urothelial carcinoma. Subsequently, he underwent radical cystoprostatectomy, which showed urothelial carcinoma with lack of cohesion, plasmacytoid variant, positive for citokeratin 7 (CK7), citokeratin 20 (CK20) and trans-acting T-cell-specific transcription factor (GATA-3), and negative for E-cadherin and CD138. It is important to recognize the plasmacytoid variant of the invasive urothelial carcinoma, since it avoids a potential misdiagnosis of metastatic cancer.

RESUMO Carcinoma urotelial invasor da bexiga, variante plasmocitoide, é uma entidade rara, com poucos casos descritos na literatura. Relatamos o caso de um homem, 79 anos, submetido à resseção transvesical de tumor da bexiga, cuja histologia revelou carcinoma urotelial de alto grau pT1. Posteriormente, foi submetido à cistoprostatectomia radical, que mostrou carcinoma urotelial invasor, descoeso, de tipo plasmacitoide, positivo para citoqueratina 7 (CK7), citoqueratina 20 (CK20) e fator de transcrição de ação"trans" específico de células T (GATA-3) e negativo para E-caderina e CD138. É importante reconhecer a variante plasmocitoide do carcinoma urotelial invasor, uma vez que se evita potencial diagnóstico errado de doença metastática.

Inflammatory myofibroblastic tumour arising incidentally as a polypoid lesion in the gallbladder / Tumor miofibroblástico inflamatório surgindo incidentalmente como lesão polipoide na vesícula biliar

ABSTRACT Inflammatory myofibroblastic tumour (IMT) is a rare mesenchymal neoplasm that usually originates from abdominal soft tissues. A female patient aged 50 years presented with a 1.2 cm gallbladder polyp. The microscopic study showed spindle cell proliferation in an edematous background rich in lymphocytes and plasma cells. Immunohistochemistry showed positivity for vimentin, smooth muscle actin, and anaplastic lymphoma kinase (ALK), and negativity for other markers. Fluorescent in situ hybridization (FISH) revealed ALK gene rearrangement. The diagnosis was IMT of the gallbladder, a unique case considering that it was identified at the early stage of development of these neoplasms.

RESUMO Tumor miofibroblástico inflamatório (IMT) é uma neoplasia mesenquimatosa rara, geralmente com origem nos tecidos moles abdominais. Uma paciente do sexo feminino com 50 anos apresentou-se com pólipo da vesícula biliar com 1,2 cm. No estudo microscópico, observou-se proliferação de células fusiformes em fundo edematoso, rico em plasmócitos e linfócitos. Imuno-histoquicamente, notou-se positividade para vimentina, actina músculo liso e cinase do linfoma anaplásico (ALK), com negatividade de outros marcadores. Observou-se rearranjo do gene ALK por hibridização fluorescente in situ (FISH). O diagnóstico foi IMT da vesícula biliar, um caso único, considerando que foi identificado no estadio inicial de desenvolvimento dessas neoplasias.

Pulmonary Peripheral Carcinoids after Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia and Tumorlets: Report of 3 Cases.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and tumorlets are neuroendocrine cells proliferations smaller than 5 mm. The former confines to bronchial/bronchiolar wall, while the latter broke through epithelial basement membrane. The authors present 3 cases of DIPNECH and tumorlets associated with a typical peripheral carcinoid tumor without underlying lung disease. The patients presented with nonspecific pulmonary symptoms: 3 females, 60, 72, and 84 years old, whose CT-scans showed well-defined pulmonary nodules, 2.2, 1.6, and 1.4 cm, respectively; first patient was submitted to lobectomy and the others underwent surgical biopsy. Whitish/brownish lobulated tumors corresponded to typical carcinoids (less than 2 mitoses/2 mm(2) and without necrosis); polygonal/elongated cells under lobular pattern expressed CD56, chromogranin A, synaptophysin, and CK7; Ki-67 positivity was between 1 and 3%. Bronchial/bronchiolar wall neuroendocrine cell hyperplasia and several neuroendocrine nodules under 5 mm, with identical morphologic and immunoexpression, were observed, without lung disease. Typical carcinoid associated with DIPNECH and tumorlets without other pulmonary diseases is rare. Sporadic cases may recall embryonal neuroendocrine differentiation potentiality to develop peripheral hyperplasia, most commonly in underoxygenated parenchyma. The described cases are elucidative of peripheral spectrum of neuroendocrine cell tumour evolution, reinforcing higher female incidence as in central carcinoids, still without a clear preneoplastic lesion.