Oval Nuclei Research Articles

Tumores neuroendócrinos pancreáticos: revisão histopatológica

Introduction: Pancreatic neuroendocrine tumors are considered rare. They are classified into functioning and non-functioning. Objective: To define and classify pancreatic neuroendocrine tumors according to their histopathological and immunohistochemical evaluation, associated with diagnostic criteria. Method: This is a narrative review of publications found in PubMed, SciELO and Google Scholar. Results: These tumors can be well or poorly differentiated and have distinct microscopic characteristics. Well-differentiated cells are small in shape, have uniform round or oval nuclei, finely granular cytoplasm indicating strong secretory capacity, and maintain the organoid structure. Presence of tumor necrosis, increased mitotic activity and high Ki-67 index indicate a high probability of neuroendocrine neoplasia. Chromogranin A and synaptophysin favor the diagnosis of well-differentiated. The positive staining of BCL 10 together with the absence of expression of chromogranin A and synaptophysin show poor tumor differentiation. The presence of positive staining for hormone expressions does not define the tumor as functioning. Conclusion: There was an increase in the diagnosis of pancreatic neuroendocrine tumors with the use of imaging techniques and awareness of the disease. Histopathological analysis with immunohistochemistry, especially when there are consuming symptoms, can indicate the type of carcinoma and lead to the most appropriate treatment.

PACAP Controls Endocrine and Behavioral Stress Responses via Separate Brain Circuits

BackgroundThe neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) is a master regulator of central and peripheral stress responses, yet it is not clear how PACAP projections throughout the brain execute endocrine and behavioral stress responses. MethodsWe used AAV (adeno-associated virus) neuronal tracing, an acute restraint stress (ARS) paradigm, and intersectional genetics, in C57BL/6 mice, to identify PACAP-containing circuits controlling stress-induced behavior and endocrine activation. ResultsPACAP deletion from forebrain excitatory neurons, including a projection directly from medial prefrontal cortex to hypothalamus, impairs c-fos activation and corticotropin-releasing hormone (CRH) messenger RNA elevation in the paraventricular nucleus after 2 hours of restraint, without affecting ARS-induced hypophagia, or c-fos elevation in nonhypothalamic brain. Elimination of PACAP within projections from lateral parabrachial nucleus to extended amygdala, on the other hand, attenuates ARS-induced hypophagia, along with extended amygdala fos induction, without affecting ARS-induced CRH messenger RNA elevation in the paraventricular nucleus. PACAP projections to extended amygdala terminate at protein kinase C delta type (PKCδ) neurons in both the central amygdala and the oval bed nucleus of the stria terminalis. Silencing of PKCδ neurons in the central amygdala, but not in the oval bed nucleus of the stria terminalis, attenuates ARS-induced hypophagia. Experiments were carried out in mice of both sexes with n ≥ 3 per group. ConclusionsA frontocortical descending PACAP projection controls paraventricular nucleus CRH messenger RNA production to maintain hypothalamic-pituitary-adrenal axis activation and regulate the endocrine response to stress. An ascending PACAPergic projection from the external lateral parabrachial nucleus to PKCδ neurons in the central amygdala regulates behavioral responses to stress. Defining two separate limbs of the acute stress response provides broader insight into the specific brain circuitry engaged by the psychogenic stress response.

Clear cell sarcoma of soft tissue arising in the supraclavicular region: A cytological diagnosis

Clear cell sarcoma of soft tissue is a rare malignant neoplasm which constitutes about 1% of soft tissue tumors. It most commonly arises in the distal extremities of young adults. Peak incidence is in the third decade. More commonly seen in women than men. A 30 year old female presented with swelling in right supraclavicular region associated with pain since 3 months. CT scan findings revealed irregular and non-enhancing, hypodense lesion measuring 2.5x2x1cm in right supraclavicular region. Cytological features revealed abundant cellularity comprising of atypical cells mainly dispersed singly and arranged in loose cohesive groups. The cytoplasm was abundant, vacuolated at places, pleomorphic round to oval nucleus, placed centrally to eccentrically with prominent nucleoli. Diagnosis of malignant mesenchymal neoplasm was made on the basis of the cytomorphological details. Clear cell sarcoma was included in the differential diagnosis. Cytomorphological diagnosis was confirmed by histological and immunohistochemical diagnosis. When cytology of a soft tissue tumor shows high cellularity alongwith dispersion and loosely cohesiveness of cells, nuclear pleomorphism and conspicuous nucleoli, diagnosis of clear cell sarcoma may be considered.

Accuracy of different cytoarchitectural features in the diagnosis of papillary thyroid carcinoma by fine needle aspiration

Fine needle aspiration (FNA) has about 90% diagnostic accuracy for papillary thyroid carcinoma (PTC) in an adequate sample. Ignorance of relative significance of individual cytologic features may lead to misdiagnosis due to reliance on a single or few features. Our objective was to determine the usefulness of individual and most appropriate combined cytologic features, for diagnosis of PTC. H&E stained FNA smears of fifty cases each, of consecutive histologically confirmed PTC and benign thyroid cases (controls), reported over 3 years, were retrieved from the files. A total of 31 architectural, cytological and background features were assessed, blind to the final diagnosis and compared amongst the two groups. The statistical significance (p<0.05) of each parameter was determined by chi-square and odds ratio and combinations quality assessed by ROC curves.: Twenty features were found to be statistically significant. Fourteen highly significant (p<0.000) features included flat syncytial sheets, anatomical borders, true papillae, cellular swirls, individually dispersed cells with eosinophilic cytoplasm, anisonucleosis, elongated oval nuclei, powdery chromatin, nuclear outline irregularity, thickened nuclear membranes, crescent shaped nuclei, intranuclear inclusions, histocytoid cells and soap bubble cytoplasmic vacuolation. The six statistically significant features (p<0.05) included micro-acinar structures, cellular crowding, nuclear overlapping, nuclear grooves, squamoid cells and bubble gum colloid. The control group also showed some of these single cytologic features. All the combinations of ≥ 4 features had a statistical significance of p=0.000 and specificity and PPV of 100% with ROC showing excellent results. Using correct combination of cytologic features will increase accuracy of FNA diagnosis of PTC.

Epithelioid inflammatory myofibroblastic sarcoma: a pitfall in the differential diagnosis of ALK-positive anaplastic large cell lymphoma.

An 18-year-old female presented with a 4.5 cm abdominal mass. Biopsy showed sheet-like growth of large tumor cells with round to oval nuclei, 1-2 nucleoli, and abundant cytoplasm. Immunohistochemistry showed strong, uniform CD30 staining and cytoplasmic ALK staining. B-cell markers (CD20, CD79a, PAX5, kappa/lambda) and T-cell markers (CD2, CD3, CD4, CD5, CD43, granzyme B, T-cell receptor-β) were negative. Other hematopoietic markers (CD45, CD34, CD117, CD56, CD163, EBV) were negative, but CD138 was positive. Non-hematopoietic markers showed desmin positivity and negativity for S100, melan A, HBM45, PAX8, PAX2, WT1, MYO-D1, myogenin, pancytokeratin, and CAM5.2. Sequencing identified PRRC2B::ALK fusion. A diagnosis of epithelioid inflammatory myofibroblastic sarcoma (EIMS) was made. EIMS is a rare, aggressive form of inflammatory myofibroblastic tumor typically presenting in children and young adults. The tumor comprises large epithelioid cells that express ALK and often CD30. ALK-positive ALCL has a similar age range and also is a large-cell tumor expressing CD30 and ALK. Other ALK-positive neoplasms (e.g., carcinomas, ALK-positive large B-cell lymphoma, ALK-positive histiocytosis) typically lack CD30 and have distinct clinicopathologic features that aid diagnosis. Hematopathologists need to distinguish EIMS from ALK-positive ALCL, which frequently shows loss of pan-T-cell antigens. Careful morphologic evaluation for the hallmark cells of ALCL and comprehensive phenotyping are critical to avoid this diagnostic pitfall. If known, the ALK rearrangement partner gene may also provide diagnostic clues; for example PRRC2B::ALK and RANBP2::ALK occur in EIMS but not ALCL.

Oncocytic Papillary Cystadenoma, an Unusual Variant Presenting as a Laryngeal Ventricular Cyst.

Cystadenoma arising from the larynx is a rare benign minor salivary gland tumor that can show mucinous or papillary morphology. The epithelial lining of the salivary gland tumor can present with oncocytic features, which is attributed to an increased number of mitochondria. We present a rare case of oncocytic papillary cystadenoma (OPC) of the larynx which has a combination of these features. The WHO defines OPC tumors as entities which closely resemble Warthin tumor, but lack its classic lymphoid component. The immunohistochemical profile and molecular genetic features are largely unknown. We present an 84-year-old female, former smoker, who presented with progressive dysphonia, dysphagia, and shortness of breath. Laryngoscopy revealed a large, smooth mass originating from the ventricle of the right vocal fold. Subsequent biopsy demonstrated cyst wall fragments lined by a bilayer of large columnar to cuboidal oncocytic cells that had granular eosinophilic cytoplasm, round to oval nuclei with finely dispersed chromatin, and small but distinct nucleoli. The surrounding stroma was slightly fibrotic with scant lymphoid elements. No nuclear pleomorphism, increased mitosis, or necrosis was identified. In the larynx, benign salivary gland tumors are rare and less frequent than malignant neoplasms. Awareness of rare benign entities like OPC help ensure proper management and aid in avoiding unnecessary therapy.

Ultrastructural study for the gonadotrophs and somatotrophs of the pituitary gland in aging rabbits of local bread (oryctolagus cuniculus)

Eighteen rabbit of local bread were classified into3 groups A, B, and C
 Group A were 6 rabbits of age one year
 Group B were 6 rabbits of age three year
 Group C were 6 rabbits of age five year
 The whole animals were accomidated for one month before the study, after that the whole animals were exposed to intensive dose of chloroform and then scarified to obtain the pituitary gland by doing anatomical technique EM processing technique. was done and finally the pituitary gland were examined at the anterior lobe ( pars distalis ) to demonstrate the somatotrophes and gonadotrophes ( FSH and LH ) secreting cells .
 The present study revealed that somatotrophes and gonado trophes were containing spherical and oval nuclei at one year of age with presence of abundant secretary granules in its cytoplasm associated with Golgi apparatus, these structures were decreased in number and size proportionally with increase of the age of animal at 3 and 5 years .

Low-grade oncocytic tumour (LOT) of the kidney is characterised by GATA3 positivity, FOXI1 negativity and mTOR pathway mutations.

Aims: We present a 5-case series of low-grade oncocytic tumour of the kidney to further discuss their clinicopathological characteristics. Methods and results: Five patients were included in this study. There were three females and two males aged 45-66years, with a median age of 65years. Four tumours were located in the right kidney, and one was located in the left kidney. Most of the tumour sections were yellow-brown in colour. Tumour sizes ranged from 2.5 to 4.5cm, with a median size of 3cm. Microscopically, the tumours were well-circumscribed but lacked a fibrous capsule; the tumours consisted of monomorphous oncocytic cells arranged mainly in solid and nested architectural patterns. The tumour cells had uniformly round to oval nuclei and often had perinuclear halos but lacked significant irregularities. Immunohistochemically, the tumour cells showed a diffuse and strong positivity for CK7 and were negative for CD117. The tumour cells were also positive for GATA3, E-cadherin, Pax-8, Succinate dehydrogenase B (SDHB) and Fumarate hydratase (FH), and negative for vimentin, Carbonic anhydrase 9 (CA9), CD10, P504s, CK20, TFE3, TFEB, HMB45, ALK and Forkhead box protein I1 (FOXI1). Next-generation sequencing identified genetic variations in these tumours, including MTOR gene mutations (4/5) and PIK3CA gene mutation (1/5). All patients were alive without disease progression at a median follow-up of 32months (range 10-57months). Conclusion: LOT is an emerging renal entity of indolent behaviour that has morphologic overlap with some renal tumours with eosinophilic cytoplasm, primarily with oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma. Familiarity with the distinctive morphological features, immunophenotype and molecular genetics of LOT helps avoid misdiagnosis.

Perivascular epithelioid cell tumor of the uterine cervix identified on the liquid-based cytology: a case report

BackgroundPerivascular epithelioid cell tumor (PEComa) occurring in the female genital tract are rare, and typically found in the uterine corpus. PEComa occurring in the cervix is extremely rare, and very few cases have been reported till now. Cytological diagnosis of cervical PEComa is even rarer. So far, only two cases of PEComa diagnosed by conventional cervical smears have been reported.Case presentationA 55-year-old postmenopausal woman presented with abnormal vagina discharge for 3 months. A liquid-based cytology test was performed. Microscopically, some loosely cohesive epithelioid cells were uniform with abundant clear cytoplasm, showing predominantly round or oval nuclei with finely stippled chromatin. Distinct round nucleoli were visible in some cells, notably with numerous melanin pigments in the cytoplasm. The cytopathological features were well correlated with cell block and histopathological findings. Upon immunohistochemistry (IHC), the tumor cells were positive for HMB45 and TFE3, focally positive for MelanA, while negative for muscle marker. Fluorescence in situ hybridization (FISH) confirmed TFE3 gene rearrangement. The final pathological diagnosis was PEComa identified by the liquid-based cytology, cell block, cervical biopsy, IHC and FISH result. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy and was followed up for 2 years with no evidence of disease.ConclusionThe cytologic characteristics of the tumor can provide sufficient clues for PEComa diagnosis, which includes loosely cohesive, epithelioid morphology with abundant clear or eosinophilic cytoplasm, low-grade nuclear atypia, cytoplasmic melanin pigments. This will help cytopathologists to recognize this rare tumor that occurred in the cervix, and the combination of predictive morphology evaluation, immunophenotype, and molecular testing can achieve the definitive diagnosis of PEComa.

What is your diagnosis? Perineal swelling in a dog.

What is your diagnosis? Perineal swelling in a dog.

Chondroblastoma: Cytomorphologic Analysis of 10 Cases with Review of the Literature

Introduction: Chondroblastoma (CB) is a rare, benign cartilage-producing tumor, typically affecting the epiphysis of long bones in skeletally immature individuals. There have been only limited case reports describing the cytomorphologic features of this tumor, and thus the cytopathologic diagnostic criteria are controversial. Herein, we report the cytologic findings of 10 CB cases, discuss the diagnostic criteria and critical differential diagnosis, along with a comprehensive review of the literature. Methods: We performed a retrospective search of our cytopathology and surgical pathology databases for cases diagnosed as CB that had corresponding cytology specimens from four large medical institutions. All available cytopathology specimens were retrieved and reviewed. Clinicopathologic and radiologic data were recorded. Results: Ten cases were retrieved from 8 patients aged 15–42 years (mean, 24 years), five of whom were males. Eight cases represented primary tumors while 2 cases were recurrences. Three cases occurred in the femur, two cases occurred in the humerus, while 1 case occurred in each of the glenoid, talus, and proximal phalanx of the 3rd toe. The cytologic diagnosis of CB was achieved in 7 cases. The neoplastic mononuclear cells were present in all cases and their cytologic features were similar. These cells displayed round to oval eccentric nuclei, evenly distributed chromatin, and inconspicuous nucleoli; few of which had nuclear indentations. Multinucleated giant cells were present in 9 cases (90%). Fragments of chondromyxoid matrix were present in 4 cases on cytologic preparations (40%). Cell blocks were available in 8 cases. Mononuclear and multinucleated giant cells were present in all adequate cell blocks and their cytologic features were identical to those seen in the smears. The chondroid matrix was present in only three of the adequate cell blocks (43%). Conclusion: We concluded that with the appropriate clinical and radiologic setting, the diagnosis of CB can be achieved on cytology if characteristic chondroblasts are present. The presence of chondromyxoid matrix is a helpful clue but is not necessary for the diagnosis. As in surgical pathology, cytologic evaluation of bone tumors should be interpreted in conjunction with clinical and radiologic findings.

Влияние введения мексидола на фоне 60-дневного воздействия тартразина на ультраструктуру эндокриноцитов коркового вещества надпочечных желёз крыс

Methods. In the experiment, 30 white mature rats were divided into 5 groups: Group 1 — control, Group 2 and Group 3 — rats exposed to tartrazine at the rate of 750 and 1500 mg/kg for 60 days. In the Group 4 and Group 5, mexidol was injected intramuscularly at the rate of 50 mg/kg against the background of the conditions of the Group 2 and Group 3. Electron microscopic examination of the adrenal glands was performed according to the standard protocol. Results. In the Group 2, epithelial cells of the glomerular and fascicular zones have a round or oval nucleus with uneven contours. The nucleus contains accumulations of heterochromatin under the karyolemma and in the karyoplasm. Large mitochondria with vesicular cristae are observed in the cytoplasm. The cisterns of the smooth endoplasmic reticulum are poorly developed. Lipid inclusions are located in groups or singly. In the Group 3, mitochondria with partially destroyed cristae were detected in the cytoplasm of endocrinocytes of the zona glomerulosa, and in the epithelial cells of the zona fasciculata, loosely packed lamellar structures were detected in the center or periphery of mitochondria, as well as cells with apoptosis. Endocrinocytes of the zona reticularis have a small size, an oval nucleus with slightly tortuous contours and accumulations of heterochromatin in the karyoplasm in the rats of the Group 2. Mitochondria were large and medium in size with spherical cristae in cross section, the cisterns of the smooth endoplasmic reticulum are unevenly expanded and fill the gaps between mitochondria. In the Group 3, almost half of the large mitochondria have densely packed lamellar structures along the periphery or in the center. Conclusion. The above-established ultramicroscopic features of endocrinocytes of the adrenal cortex after 60 days of exposure to tartrazine indicate a decrease in their secretory activity, which depends on the dose of the supplement administered. The introduction of mexidol against this background helps to restore the disturbed ultramicroscopic picture of cells to control values, which is more pronounced in the Group 4.

Evaluation of Risk Factors for Malignancy Obtained by Means of Fine Needle Aspiration Biopsies in Thyroid Nodules and Surgical Outcomes of Patients with Bethesda Category III (AUS/FLUS).

Background: The nodules diagnosed as the "atypia of undetermined significance" category are a heterogenous group with an indeterminate risk of malignancy. This study aimed to perform a detailed cytological examination of the preparations to determine the cytomorphological criteria that may be useful to distinguish benign cases from malignant ones, correlate them with ultrasonographic findings, and compare them with the final pathological result in surgically treated patients. Methods: The preparations of patients classified as Bethesda 3 were re-evaluated; presence or absence of one of 11 parameters (hypochromasia, oval nucleus, colloid, intra-nuclear pseudoinclusions, nuclear grooving, nuclear moldering, isolated nuclear enlargement, nuclear irregularity, nuclear size, microfollicular pattern, distinct nucleoli) and correlating with surgical outcomes by adding ultrasonographic findings to statistically significant parameters. Results: Two hundred and six fine needle aspirations (FNA) procedures were classified as Bethesda 3. A total of 53 patients underwent surgery; 28 (52.8%) of them were benign, and 25 (47.1%) were malignant. Thirty-two (15.5%) accepted direct surgery; 53 patients underwent repeat FNA at 3-6 month intervals and those with malignancy and repeated Bethesda 3 interpretation were operated. One hundred twenty-one (69.5%) patients who did not undergo biopsy were invited for ultrasonographic controls at 3-6 month intervals. Among the 11 cytomorphologic parameters evaluated, 7 were found to be statistically significant (p 0.05) with malignancy. When at least 3 of these parameters were positive, the malignancy rate was 92%. Malignancy was present in 19 (61.3%) of the patients with high risk nodules (TIRADS = 4), compared to only 6 (35.8%) of the low-risk (TIRADS = 3); there was a significant correlation between the presence of malignancy and TIRADS score (p=0.015). The preparations that displayed nucleus atypia were closely associated with the ultrasonographically high-risk group. Conclusion: The parameters indicating nuclear atypia, presence of more than 3 cytomorphological factors, TIRADS score 4 were significantly associated with malignancy; nuclear atypia were closely associated with the ultrasonographically high TIRADS. No significant correlation was found between the presence of "microfollicular pattern" and malignancy.

Occurrence of ocular and adnexal neoplasms in canines with special reference to pigmented sebaceous gland epithelioma of eyelids

The eyelid tumours are uncommon in dogs. In the present study, out of 102 ocular and adnexal samples from the dogs examined for a period of 2.5 years, 11 cases (10.78 per cent) were neoplastic in nature. The major location of the neoplasms was eyelids (8/11). One case (0.98 per cent) was diagnosed as pigmented sebaceous gland epithelioma. The tumour mass was present in the palpebral conjunctiva of the lower eyelid near the medial canthus of the left eye in a five-yearold Labrador dog. Grossly, the tumour mass appeared to be a greyish-black, firm, cauliflower-like growth. The mass was resected and submitted for histopathology. Microscopic examination of the mass showed a preponderance of basaloid reserve cells in the tumour tissue. The proliferating reserve cells formed irregular islands or trabeculae separated by thin fibrous connective tissue. They showed minimal to no pleomorphism, scanty amphophilic cytoplasm and oval nuclei. Melanin-containing cells were frequent, while mature sebocytes were infrequent. Mitotic figures were occasional. Pigmented sebaceous gland epithelioma was diagnosed based on gross and histopathological features. Apart from this, neoplasms such as fibrosarcoma, meibomian gland adenocarcinoma, well differentiated squamous cell carcinoma, papilloma and non-pigmented sebaceous gland epithelioma involving eyelids, histiocytoma of third eyelid, periglobular lymphoma and leukemic infiltration of choroid were also recorded. The present research underlines the lower incidence of eyelid tumours in dogs.

Cytodifferentiation of pinealocytes (I and II) and astrocyte types of mature male sheep epiphysis cerebri with special emphasis on the presence of neuronal and pigmented-like cells.

The epiphysis cerebri (pineal gland) is a small-sized, photo neuroendocrine organ in the brain of most vertebrates. Their effect is through secretion of melatonin, a serotonin-derived hormone which is stimulated by darkness and inhibited by light and modulates the circadian rhythm; light and dark cycle like a biological clock, sleep patterns (sleep-wake cycle), and sexual development. This study aimed to identify and differentiate the different cell types filling the pineal gland parenchyma of mature male sheep. Pineal glands were collected and sliced parasagitally then processed histologically for light and electron microscopic examinations. Two main cell types; pinealocytes and astrocytes were recognized within the gland parenchyma. Pinealocytes were the chief parenchymatus cells that occupied the largest volume of the gland and were classified according to the nuclear pictures (activity status) into two subtypes; pinealocytes I (pale subtype, active) and II (dark subtype, inactive). Astrocyte neuroglial cells had cytoplasmic processes which form a huge supportive framework between the pinealocytes and clarified two types; type I were elongated cells with elongated snake shaped nucleus and type II were smaller in size, with oval nuclei. Another marginal cell type was identified as a neuron-like cell which appeared larger in size than others and distributed sporadically, has eccentric oval nucleus with prominent nucleoli and single, long cytoplasmic process that branched at its terminal forming T-shaped process looks like pseudo unipolar neuron. Moreover, aggregations of pigment granules were markedly observed in the intercellular spaces and also near the blood capillaries. With transmission electron microscope (TEM) a special characteristic feature of pinealocytes; synaptic ribbons were recognized that appeared as bands of electron-dense material with several synaptic spherules; vesicles adjacent to its surface helping in the multivesicular release. The gland parenchyma revealed two main cell types; pinealocytes and astrocytes. Each one was subdivided into two subtypes; I and II. The first one was classified according to their nuclear pictures (activity status) and the second one was according to their shape, size, and cytoplasmic processes. Other cell types were also identified as neuronal and pigmented-like cells in the pineal matrix.

NUT Carcinoma: A Diagnostically Challenging Rare Entity with an Aggressive Course: A Case Series

Nuclear Protein in Testis (NUT) carcinomas are rare, extremely aggressive, poorly differentiated squamous carcinoma, characterised by the presence of NUT gene (NUTM1) rearrangement. NUT carcinoma most commonly arises in head and neck region and thorax however, they can occur in other parts of the body also. Here, we are presenting a case series of three cases of NUT carcinoma.All patients were females with disease involving head and neck region. The first case was an eight-year-old girl. The second case was a 36-year-old woman. The third case was a 61-year-old woman. Histopathology of all cases showed poorly differentiated neoplasm, comprising of sheets of monotonous cells with minimal indistinct, clear cytoplasm, round to oval nuclei with prominent nucleoli. High mitotic rate with areas of tumour necrosis were also present. Areas of abrupt keratinisation classically described in this entity were seen in two of the cases. Speckled nuclear positivity for NUT1 monoclonal antibody by immunohistochemistry, which is sensitive and specific for diagnosis was observed in all three cases. There is no definite treatment for this disease, and most patients respond poorly to conventional chemotherapy and radiation. Targeted therapy targeting the BRD4 portion of BRD4-NUT, termed BET bromodomain inhibitors, are in clinical trials. Two of our patients succumbed to disease within one year of diagnosis. Third patient is on follow-up for eleven months after diagnosis.

Recurrent IDH2 Mutations in Salivary Gland Striated Duct Adenoma Define an Expanded Histologic Spectrum Distinct From Canalicular Adenoma.

Striated duct adenoma (SDA) is a rare salivary gland neoplasm defined by histologic similarity to normal striated ducts. However, doubt persists about whether SDA represents a genuine entity distinct from canalicular adenoma and if a malignant counterpart exists. This study aims to evaluate the molecular underpinnings of SDA to clarify its pathogenesis and classification. We identified 10 SDA and 2 tumors called low-grade adenocarcinoma not otherwise specified that were retrospectively recognized to resemble SDA. All cases showed recurrent histologic features including (1) discrete monophasic tubules, (2) tall columnar eosinophilic cells, (3) monotonous oval nuclei, and (4) scant fibrous stroma, and most were positive for S100 protein (91%), SOX10 (80%), and CK7 (80%). Although 1 case was previously called adenocarcinoma based on interdigitation with normal acini, this pattern was also seen in some SDA, and likely does not indicate malignancy; the significance of growth surrounding nerve in 1 other case is less clear. Targeted sequencing identified IDH2 R172X mutations in all 8 cases with sufficient tissue, with positivity for IDH1/2 mutation-specific immunohistochemistry in 9 cases stained. In contrast, 5 canalicular adenomas lacked IDH2 mutations or other oncogenic alterations. Overall, IDH2 R172X mutations are a defining feature of SDA that, in combination with its recognizable pathologic profile, confirm it is a unique entity separate from canalicular adenoma. IDH1/2 mutation-specific immunohistochemistry may provide a convenient tool to facilitate diagnosis. Both morphology and IDH2 mutations raise parallels between SDA and breast tall cell carcinoma with reverse polarity.

CD 30 Positive Large B Cell Lymphoma, Mimicking Metastatic Carcinoma: A Case Report

Diffuse large B-cell lymphoma can selectively and predominantly infiltrate lymph node sinuses this pattern has been recognized as an unusual morphologic variant of this entity. Sinusoidal large B-cell lymphomas with CD30 expression are even more rare.We present a 63-year-old female, who came in with a chief complaint of mass in the axillar region for 2 months. The lymphnode ultrasound revealed multiple suspicious lymphadenopathes in the right upper jugular, both axilla and inguinal region sized 0.5 cm to 3 cm. HE staining from the axillar mass biopsy showed sinusoidal growth pattern, composed of large atypical cells, round to oval nuclei, pleomorphic, and prominent nucleoli, with some large bizzare cells mimicking hallmark cells, and we proposed it as metastatic carcinoma with a differential diagnosis of Anaplastic Large Cell Lymphoma, but the immunohistochemical staining showed uncommon feature of Large B Cell Lymphoma with CD 30 expression.

INNV-28. A PILOT STUDY EVALUATING THE FEASIBILITY OF USING AN ULTRA-FAST DIGITAL CONFOCAL MICROSCOPY SCANNER FOR REAL-TIME INTRA-OPERATIVE BRAIN TUMOUR DIAGNOSIS

Abstract INTRODUCTION Real-time intra-operative brain tumour tissue analysis in the operating room (OR) can shorten turnaround times and facilitate repeated sampling; the latter can improve diagnostic accuracy and guide resection to maximise extent. We evaluated the feasibility of using an ultra-fast confocal microscopy scanner (Histolog®, SamanTree Medical SA) in the OR for real-time intra-operative brain tumour tissue diagnosis. This study is the first use of Histolog® on primary human brain tissue globally. METHODS An observational pilot study with varying brain tumour types was conducted in a tertiary UK brain tumour centre. Multiple, freshly excised tissue samples were stained with Acridine Orange, and images captured within 60 seconds on Histolog® in the OR in parallel to current diagnostic pathways. A Consultant Neuropathologist performed a blinded correspondence assessment between Histolog® and current gold standard histopathology. Qualitative logging of diagnostic features was performed. RESULTS Cases studied (n=12) included glioma, metastasis, meningioma, schwannoma, and pituitary adenoma. Concordance between Histolog® and traditional (frozen section) intra-operative histopathological diagnosis was 83% (10/12 cases). One Histolog® case demonstrated superior diagnostic accuracy to frozen section. Histolog® images demonstrated specific diagnostic features such as clusters of cohesive epithelioid cells (metastatic carcinoma), sheet-like variably cellular and pleomorphic cells (gliomas), diffuse sheet-like monomorphic round nuclei (pituitary adenoma), elongated spindle cells (schwannoma), and nodular architecture and oval nuclei (meningioma). DISCUSSION Ultra-fast confocal microscopy scanning with Histolog® is feasible in the OR and Histolog® image resolution is adequate to identify histopathological features necessary for intra-operative brain tumour diagnosis. Training and clinico-radiological details are important in minimising discordance. A larger study with greater numbers and tumour types will now be performed to define an optimal scanning protocol and determine the strengths and limitations of the technology. Future studies should investigate the effect of real-time margin zone analysis on extending resection.

Serous Cystadenocarcinoma of Pancreas: A Rare Find

Abstract Introduction/Objective Pancreatic cystic neoplasms comprise 1-2% of pancreatic lesions and most of these lesions are cystadenomas. Serous cystadenocarcinoma is an extremely rare but known malignant condition described in the literature and the diagnosis is restricted to cases with distant metastasis of tumor beyond the pancreas. Per WHO, cytologic atypia, vascular, perineural, and adjacent organ and lymph node involvement by direct spread are insufficient for the diagnosis of serous cystadenocarcinoma. Methods/Case Report We report an interesting case of serous cystadenocarcinoma of pancreas in a 55-year-old male with medical history of prostate cancer was found to have a 15 cm mass pancreatic tail suspicious for neuroendocrine tumor and 5 small hepatic lesions suspicious for metastasis. The patient underwent subtotal pancreatectomy and splenectomy, and wedge resection of liver lesions. On gross examination, a yellow cystic mass was present in the pancreatic tail measuring 13.2 cm in the maximum dimension. H&E slides from the pancreas and liver demonstrated a neoplasm composed of cystic and solid areas, within a background of fibrosis and focal hemorrhage. Cystic areas showed microcysts composed of cells with clear cytoplasm and round to oval bland nuclei. Solid areas demonstrated almost no microcysts but sheets and clusters of cells with clear to scant cytoplasm, oval to round nuclei, few areas of atypical hyperchromatic cells, and occasional mitosis. Very focal clusters and cords of neuroendocrine cells, constituting less than 5% of the tumor volume were also identified. Immunohistochemical stains demonstrated the neoplastic cells both in cystic and solid areas were positive for CK7, CK19, MUC6, and inhibin. Ki67 demonstrated an overall proliferation index of 3%. Chromogranin and synaptophysin were negative within the solid and cystic components of the tumor, however, showed positive staining within neuroendocrine foci. Neoplastic cells were negative for all other tested markers including beta-catenin, ER, Hep-par 1, HMB45, IMP3, MART-1, PAX-8, and trypsin. RB1 expression was retained within neoplastic cells. Results (if a Case Study enter NA) N/A. Conclusion The differentiation between benign and malignant serous cystadenoma both histologically and clinically may be very difficult as some cases of serous cystadenocarcinoma may not show overt cytologic atypia. The presence of metastasis, which most often occurs in the liver is required for the diagnosis of serous cystadenocarcinoma.