Cytologic features of mesenchymal, melanocytic and haematolymphoid tumours of the central nervous system and metastases.

The current World Health Organization (WHO) classification of central nervous system (CNS) tumours includes several neoplasms that, while occurring in this location, are more frequently seen extracranially. These include mesenchymal, melanocytic and haematolymphoid neoplasms, as well as metastases. A few of these entities are exclusive of the CNS and have no extracranial counterpart. Despite their diverse histogenesis, these neoplasms share a peculiar predilection for involving meningeal structures. In fact, in the context of an intraoperative pathologic consultation of a meningeal tumour, virtually all these entities should be considered as potential diagnoses. Metastases in the CNS are very common. Most are carcinomas that cytologically resemble their site of origin. Loss of differentiation with cell dissociation and anaplasia and presence of accompanying fibrillary brain parenchyma can be a source of diagnostic problems. In this review, we intend to show the most relevant cytologic features of these tumours, and it is especially aimed at their analysis during intraoperative studies.

Cytologic features of meningioma: An analysis of common and uncommon subtypes and diagnostic difficulties during intraoperative procedures.

Despite common histogenesis meningiomas have a wide morphologic spectrum, and the World Health Organization (WHO) recognizes 15 subtypes. They are the most common brain tumour in adults and typically have an extra-axial location. Although there have been important advances in the molecular biology of meningiomas its diagnosis is based on histopathologic features. The great majority are benign WHO grade 1 tumours. There are specific criteria for assigning WHO grade 2 and 3 that can be applied to all meningioma subtypes. Regardless of these criteria, chordoid and clear cell morphologic subtypes are considered grade 2. WHO grade 3 tumours exhibit a very high mitotic index, frank anaplasia or specific molecular abnormalities. The impressive morphologic diversity shown by meningiomas makes them a diagnostic challenge, which can be even greater in intraoperative studies. The focus of this article is to describe and illustrate their main cytologic features, with emphasis on the most infrequent subtypes.

Cytological features of diffuse and circumscribed gliomas.

The current World Health Organization classification of gliomas is based on morphological, genetic, and molecular parameters. In this review, we intend to present the most relevant cytological features of these tumours, with a particular focus on their analysis during intraoperative studies. Rapid diagnosis is required in this context, and at present it is not possible to evaluate the genetic or molecular profile of a tumour intraoperatively. New terminology and diagnostic parameters have been introduced, but the essence of intraoperative recognition remains the same. The main challenge in astrocytoma IDH-mutant, grade 2 is recognising the tissue as neoplastic. Since glioma grades 3 and 4 are assigned based on histological and genetic variables that are not necessarily measurable on cytology, the term high-grade glioma is often used for intraoperative diagnosis. Oligodendroglioma, IDH-mutant and 1p/19q-codeleted shows peculiar cytological findings as well as the common subtypes of glioblastoma IDH-wildtype (giant cell, epithelioid, gliosarcoma and small cell). Many of the paediatric-type-diffuse gliomas have been described very recently and there are no cytological reports of proven cases. Finally, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, chordoid glioma, and astroblastoma MN1-altered constitute the group of circumscribed astrocytic gliomas. They are remarkable entities that the pathologist must be able to recognise since most are low-grade neoplasms that can show atypical morphological features.

Enigma portal: Undifferentiated thyroid malignant neoplasm in a patient with Hashimoto's thyroiditis.

Undifferentiated anaplastic thyroid tumours are uncommon and constitute a diagnostic challenge on fine needle aspiration. A case showing large, single neoplastic cells in a background of Hashimoto's disease is presented.

Cytologic features of a pleural effusion after silicone breast implant rupture.

Pleural effusion is an extremely rare complication of ruptured breast silicone implants. Rupture may be related to a recent trauma or occur spontaneously, making its diagnosis more difficult. In the few reported cases, cytology did not play a relevant role in its diagnosis. We describe and illustrate a silicone foreign body reaction in a pleural effusion. Cytologic findings were so remarkable as to permit a specific diagnosis. The patient, a 37-year-old female with a history of previous bilateral breast implant surgery was admitted because of a pleural effusion. Computed tomography scan showed a left effusion with secondary atelectasis and bilateral breast rupture with lymph node "siliconomas." Cytologic analysis of the effusion showed well-defined droplets or globules of transparent material, in addition to a microvacuolized background. Where abundant silicone droplets induced a staining artifact of the smears. These were cellular with numerous macrophages containing large vacuoles displacing the nuclei to the periphery. Some had a signet cell ring appearance, while others showed multinucleation. Flow cytometry revealed a predominant macrophagic cell population. With the increasing use of silicone breast implants, rare complications such as pleural effusion may become more common. The pathologist must consider this possibility when extracellular transparent droplets or evidence of a foreign body-type reaction are present. The artifact appearance of the smears may help to suspect it. This rare complication must be always considered when evaluating effusions in patients with silicone breast implants.

Complete spontaneous regression of a primary renal cell carcinoma. Report of a pathological proven case and review of the literature.

Regression of primary renal cell carcinoma (RCC) is a rare phenomenon and for several reasons many of the reported cases have been questioned. We present a case that can be considered a true spontaneous and complete regression of a primary RCC. A 79-year-old female underwent nephrectomy because a renal tumor. At the time of surgery image studies showed a small para-aortic lymph node. The tumor measured 3cm and was analyzed completely. Histology showed a fibro-inflammatory lesion with necrosis, foamy macrophages and inflammatory cells. No neoplastic cells were observed and the lesion was interpreted as a localized type of xanthogranulomatous pyelonephritis. One year later a CT control scan, showed that the para-aortic lymph node had increased in size to 4cm. Fine needle aspiration revealed features of clear RCC. Metastatic dissemination was limited so surgical removal of the para-aortic lymph node was performed and the cytologic diagnosis confirmed.

A comprehensive review of the "tigroid" background cytological concept: what, when, where and why?

The concept of "tigroid" background is used in cytology to describe a peculiar smear background characterized by the presence of a relatively granular, reticulated material that was described as "foamy, lazy, tiger-striped or astrakhan". It was used to describe the background seen in smears obtained from seminoma. In addition to seminoma, we now know that it can be present in different tumours, mostly carcinomas and round cell sarcomas. These share with seminoma a cytoplasm with high glycogen content and many times clear cell morphology. The "tigroid" background is seen when smears are air-dried and Romanowsky-based stains are used (May-Grunwald-Giemsa and Diff-Quik stains). It is only seen in fine needle aspiration or intraoperative squashing or scrapping samples, but not in specimens obtained from effusions or liquid-based cytology. Wet-fixed cytologic samples with alcohol or with formaldehyde tend to dissolve the background so it is not usually present in Papanicolaou stained smears. In this review, we discuss tumours in which the "tigroid" background is observed and its potential diagnostic utility and aetiology. It is interesting to remark that except for parathyroid adenoma and adenomatoid tumour all the neoplasms in which this background has been observed are malignant.

A Cytological Review of Follicular Dendritic Cell-Derived Tumors with Emphasis on Follicular Dendritic Cell Sarcoma and Unicentric Castleman Disease.

Follicular dendritic cells (FDCs) are antigen-presenting cells located in the germinal centers of the lymph nodes. Among the few tumors showing FDC differentiation are follicular dendritic cell sarcoma (FDCS) and Castleman disease (CD), more precisely the unicentric hyaline vascular (HV) variant. Both are relatively rare tumors, and the diagnostic cytological experience is limited to descriptions of isolated cases or small series. The purpose of this review is to bring together all the available cytological published information, and our personal experience, in order to obtain a global idea of the cytological features of these peculiar FDC-derived tumors. The different descriptions of FDCS are very similar, reflecting a tumor that shows repetitive and characteristic cytological features. It shows a dimorphic population of mature lymphocytes and large tumoral cells with partial spindle morphology. Most cases of HV variant of CD can be recognized as benign upon cytology, however a precise diagnosis seems more difficult. It is characterized by reactive lymphocytes mixed with vessels and FDCs, either single or forming syncytial aggregates. Both, FDCS and CD are challenging for cytological diagnosis in which a high index of suspicion is necessary for a correct preoperative assessment. Cytology is very useful for follow-up of recurrences and metastases.

Tumor-Associated Granulomas Preceding a Diagnosis of Thoracic Sarcoidosis: A Retrospective, Single-Center Cohort Study.

There is a relationship between systemic sarcoidosis (SS) and malignancy. Sarcoidosis results from an exaggerated immune response in genetically susceptible individuals. In oncologic patients with sarcoidosis, tumoral antigens and antineoplastic treatment are considered potential triggering factors. The observation of a patient with granulomas in a parotid carcinoma who later developed SS led us to review the previous tumors of patients with SS. The aim of the study is to see whether granulomas were already present in the tumors that preceded sarcoidosis. We identified 196 sarcoidosis patients, 47 of whom had previously had a tumor. We were able to review 29 cases, 12 of which showed tumor-associated granulomas (TAGs) (41.4%). This ratio is much higher than that of the normal population (4.4-13.8). We analyzed five control patients without sarcoidosis for each tumor. In conclusion, we observed an increased number of TAGs in patients who later developed SS. This finding reinforces a pathogenic relationship between SS and neoplasia. The histology of tumors in patients with SS should be reviewed in an attempt to identify granulomas.

Fine needle aspiration cytology of a myxoid adrenocortical adenoma. A case report.

The myxoid variant of adrenocortical (AC) tumors is characterized by peculiar histologic features that differ from conventional ones. It shows a prominent myxoid stromal component and is composed of small cells with mild atypia arranged in cords, pseudoglandular structures and microcysts. Reflecting the rarity of this variant, very few cytologic descriptions are available. We describe one case in a 41-year-old woman with a previous diagnosis of breast carcinoma and BRCA1 mutation. During follow-up controls, an adrenal tumor was discovered. Fine needle aspiration cytology and Tru-Cut biopsies were performed simultaneously. Smears showed numerous groups of cohesive cells of intermediate to small size. Within the largest groups, aggregates of myxoid metachromatic material were evident. This myxoid material could also be observed as isolated acellular fragments. While the cytoplasm of most tumoral cells was homogenously stained some showed small vacuoles. Histologically, the tumor grew, forming anastomosing cords, separated by myxoid material that determined microcystic spaces. Immunohistochemistry was characteristic of AC myxoid tumor. After surgery, pathologic analysis confirmed this diagnosis. The tumor showed no necrosis or invasion, had a low mitotic index (3/50 high power fields) and Ki-67 proliferative index of 15%. According to the different diagnostic systems the tumor was classified as an adenoma. In conclusion, the myxoid variant of AC tumors shows peculiar cytologic features. If unaware of the existence of this variant, it can easily be misinterpreted as a metastatic tumor.

Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage: an autopsy study with clinical correlation and review of the literature.

Pulmonary megakaryocytes participate in the pathogenesis of lung damage, particularly in acute lung injury. Although megakaryocytes are not mentioned as a characteristic histologic finding associated to pulmonary injury, a few studies reveal that their number is increased in diffuse alveolar damage (DAD). In this autopsy study, we have observed a relevant number of pulmonary megakaryocytes in COVID-19 patients dying with acute lung injury (7.61 ± 5.59 megakaryocytes per 25 high-power fields vs. 1.14 ± 0.86 for the control group, p < 0.05). We analyzed samples of 18 patients, most of whom died after prolonged disease and use of mechanical ventilation. Most patients showed advanced DAD and abnormal coagulation parameters with high levels of fibrinogen, D-dimers, and variable thrombocytopenia. For comparison, pulmonary samples from a group of 14 non-COVID-19 patients dying with DAD were reviewed. They showed similar pulmonary histopathologic findings and an increase in the number of megakaryocytes (4 ± 4.17 vs. 1.14 ± 0.86 for the control group, p < 0.05). Megakaryocyte count in the COVID-19 group was greater but did not reach statistical significance (7.61 ± 5.59 vs. 4 ± 4.17, p = 0.063). Regardless of the cause, pulmonary megakaryocytes are increased in patients with DAD. Their high number seen in COVID-19 patients suggests a relation with the thrombotic events so often seen these patients. Since the lung is considered an active site of megakaryopoiesis, a prothrombotic status leading to platelet activation, aggregation and consumption may trigger a compensatory pulmonary response.

Increased miR-7641 Levels in Peritoneal Hyalinizing Vasculopathy in Long-Term Peritoneal Dialysis Patients.

Peritoneal hyalinizing vasculopathy (PHV) represents the cornerstone of long-term peritoneal dialysis (PD), and especially characterizes patients associated with encapsulating peritoneal sclerosis. However, the mechanisms of PHV development remain unknown. A cross sectional study was performed in 100 non-selected peritoneal biopsies of PD patients. Clinical data were collected and lesions were evaluated by immunohistochemistry. In selected biopsies a microRNA (miRNA)-sequencing analysis was performed. Only fifteen patients (15%) showed PHV at different degrees. PHV prevalence was significantly lower among patients using PD fluids containing low glucose degradation products (GDP) (5.9% vs. 24.5%), angiotensin converting enzyme inhibitors (ACEIs) (7.5% vs. 23.4%), statins (6.5% vs. 22.6%) or presenting residual renal function, suggesting the existence of several PHV protective factors. Peritoneal biopsies from PHV samples showed loss of endothelial markers and induction of mesenchymal proteins, associated with collagen IV accumulation and wide reduplication of the basement membrane. Moreover, co-expression of endothelial and mesenchymal markers, as well as TGF-ß1/Smad3 signaling activation were found in PHV biopsies. These findings suggest that an endothelial-to-mesenchymal transition (EndMT) process was taking place. Additionally, significantly higher levels of miR-7641 were observed in severe PHV compared to non-PHV peritoneal biopsies. Peritoneal damage by GDPs induce miRNA deregulation and an EndMT process in submesothelial vessels, which could contribute to collagen IV accumulation and PHV.