Programmed cell death protein 1 is a marker for neoadjuvant chemotherapy response in triple-negative breast cancer

SUMMARY OBJECTIVE: Tumor-infiltrating lymphocytes are detectable in up to 75% of triple-negative breast cancer. The composition of these infiltrates may influence prognosis and is not known regarding regulatory or effector lymphocytes. The objectives of this study were to describe and quantify the composition of the tumor-infiltrating lymphocytes before and after chemotherapy (neoadjuvant chemotherapy) and to evaluate their association with complete pathological response and overall survival. METHODS: This was a retrospective observational study. Clinical and pathological data from 38 triple-negative breast cancer patients treated with neoadjuvant chemotherapy at the University Hospital (HUCFF/UFRJ), between November 2004 and November 2018, were analyzed. The Stromal tumor-infiltrating lymphocytes (Stromal tumor-infiltrating lymphocytes) have been identified on hematoxylin and eosin-stained sections according to the guidelines of the "International tumor-infiltrating lymphocytes Working Group." Immunohistochemistry studies were performed to identify T-cell subsets (i.e., CD3, CD4, CD8, and FOXP3) and T-cell exhaustion (i.e., programmed cell death protein 1). RESULTS: Statistically significant changes in stromal tumor-infiltrating lymphocyte categories were observed before and post-neoadjuvant chemotherapy, with 32% of intermediate cases becoming high. The correlation between pre-neoadjuvant chemotherapy stromal tumor-infiltrating lymphocytes and pathological response, pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy, and stromal tumor-infiltrating lymphocytes and overall survival was not statistically significant. However, we noticed an increase of cells that favor the antitumor activity (i.e., CD3, CD8, and CD8/FOXP3 ratio) and decreased levels of cells inhibiting tumor activities (i.e., FOXP3 and programmed cell death protein 1) post-neoadjuvant chemotherapy. Importantly, programmed cell death protein 1 expression pre-neoadjuvant chemotherapy showed an association with pathological response. CONCLUSION: In this study, we observed that chemotherapy significantly increases stromal tumor-infiltrating lymphocytes, CD8 T cells, as well as CD8/FoxP3 ratio. Most importantly, programmed cell death protein 1 expression before neoadjuvant chemotherapy positively correlates with pathological response suggesting the use of programmed cell death protein 1 as a prognostic marker before neoadjuvant chemotherapy.

Clinical-histopathological profile of the frontal fibrosing alopecia: a retrospective study of 16 cases of a university hospital

Abstract: Background: Frontal fibrosing alopecia is a condition of unknown origin, histologically similar to classic lichen planopilaris and generally observed in postmenopausal women with alopecia of the frontal-temporal hairline. Objectives: To describe the clinical, dermatoscopic, and histopathological characteristics and the treatment used in patients who have frontal fibrosing alopecia at the Alopecia Outpatient Clinic in a university hospital. Methods: Retrospective descriptive study performed by reviewing medical charts and biopsies of the scalp. Results: Sixteen patients were analyzed, all of them female, 93.75% of them postmenopausal, and 56.25% brown-skinned. All had frontal alopecia (100%), followed by temporal alopecia (87.5%) and madarosis (87.5%). On dermatoscopy, perifollicular erythema and tubular scales were found as a sign of disease activity. Of the patients, 68.75% had associated autoimmune diseases, including lupus, thyroid disease and vitiligo. Of the 13 biopsies from 8 patients, 10 showed microscopic aspects compatible with frontal fibrosing alopecia. Laboratory tests did not show major abnormalities and minoxidil was the most used treatment. Study limitation: Data collection limited by the study's retrospective design associated to flaws while filling in the medical charts and absence in standards to the collection and processing of the pathology and histopathological examination. Conclusions: A demographical, clinical, and histopathological description of 16 patients diagnosed with frontal fibrosing alopecia, which remains a challenging disease, of unknown origin, and frequently associated with autoimmune diseases. This study reinforces literary findings. However, more research is needed to establish the pathogenesis and effective treatments.

Evaluation of the Cutaneous Lymphoma International Prognostic Index in patients with early stage mycosis fungoides

Abstract: Background: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. TNMB system is the staging method used in MF, and it not only guides therapeutic management, but represents the main prognostic factor. In order to improve the prognostic evaluation, the Cutaneous Lymphoma International Prognostic Index (CLIPi) was proposed. Objective: To evaluate the performance of CLIPi score for prognostic analysis in patients with early stage MF. Methods: This is a retrospective cross-sectional observational study, with exploratory analysis. The outcome variables were disease progression and related death. Results: One hundred and two patients were stratified according to CLIPi score, being the majority classified as low risk. Patients with intermediate or high risk presented disease progression more frequently than those with low risk (PR: 1.2 / p = 0.004 / 95%CI: 1.0 - 1.6). The same did not occur with the variable related death. In addition, survival rates were not consistent with risk stratification. Study Limitations: Small sample and its retrospective analysis. Conclusions: Since CLIPi score was proposed, four other studies that we could consult showed conflicting results, similar to the present study. Further studies are necessary for a recommendation of its use.

Clinical and epidemiological profile of patients with early stage mycosis fungoides

Abstract: Background: Mycosis fungoides is the most common form of primary cutaneous lymphoma, with an indolent, slowly progressive course and 88% five-year survival rate. The diagnosis is challenging, especially in the early stages, and usually relies on a good clinical-histopathological correlation. Objective: The aim was to establish the clinical and epidemiological profile of patients with early-stage mycosis fungoides. Methods: This was a retrospective cross-sectional observational study with an exploratory analysis. Outcome variables were disease progression and mycosis fungoides-related death. Results: One hundred and two patients were included. The majority were white males, with a mean age of 55.6 years. Mean time from onset of lesions to diagnosis was 51.08 months. The majority of patients were classified as IB stage according to TNMB. Mean follow-up time was 7.85 years. Disease progression was seen in 29.4% of the patients. Death related to the disease occurred in 7.9% of patients. Plaque lesions, involvement of more than 10% of the body surface, altered lactate dehydrogenase and beta-2-microglobulin, and stage IB were significantly associated with disease progression, and altered lactate dehydrogenase and beta-2-microglobulin also correlated with higher frequency of deaths. Study limitations: Small sample and retrospective design. Conclusions: The clinical and epidemiological profile of patients with early-stage mycosis fungoides in our sample corroborates reports in the literature. Diagnostic delay in our series is also consistent with previous findings, but the rate of disease progression, despite treatment, was higher than reported in the literature.

Histopathological diagnosis of small melanocytic lesions suspicious for malignant melanoma

Abstract The concern about malignant skin neoplasms leads to the excision of smaller lesions. This study on small melanocytic lesions aims to evaluate the range of possible histopathological diagnoses, describe histopathological aspects, and assess the usefulness of serial histological sections. We performed a cross-sectional descriptive histopathological study examining 76 pigmented skin lesions up to 6 mm in diameter. Histopathological diagnoses included atypical melanocytic nevi (n=38), common melanocytic nevi (n=18), atypical lentiginous melanocytic hyperplasia with architectural features of atypical melanocytic nevi (n=7), lentigo simplex (n=2), and malignant melanoma (n=1). Ten cases were non-diagnostic. Cytological atypia was not an exclusive finding of atypical lesions. Examination of serial sections did not change histopathological impression. Early detection of malignant melanoma is important, but clinical and dermoscopy exams may be leading to the resection of a great number of benign lesions. Strict attention to histopathological criteria results in a large number of non-diagnostic cases.

Sarcoid-like cutaneous lesions in chronic adult paracoccidioidomycosis: report of two cases

ABSTRACT This study reports two cases of chronic paracoccidioidomycosis with sarcoid-like cutaneous lesions. The patients began the treatment in 2013 at Hospital Universitário Clementino Fraga Filho (HUCFF) of the Universidade Federal do Rio de Janeiro (UFRJ). The first case (mild form) was treated with trimethoprim-sulfamethoxazole (8 mg /kg per day, orally) for three months and, then, with half the dose for nine months; the second (moderate form), with itraconazole (200 mg per day, orally) for 12 months. We point out the rareness of the sarcoid-like cutaneous lesions and the differential diagnoses for other granulomatous diseases.