Histopathology of hepatocellular carcinoma - when and what

When do you need to take biopsies of the liver, and what information will you get is the topic of this review on hepatocellular carcinoma (HCC). If, clinically, the differential diagnosis of HCC after imaging is suggested, a biopsy has become obligatory as a diagnostic confirmation of HCC in the non-cirrhotic liver prior to definitive therapeutic interventions, as well as in a palliative therapy concept. In the case of hepatic lesions with an uncharacteristic contrast uptake, a biopsy should be performed immediately to confirm the diagnosis of HCC. After diagnosing HCC, a treatment strategy is evaluated. Further, the biopsy, or in case of surgical treatment, the resected tissue, shows us the different subtypes of HCC, with the steatohepatitic subtype being the most common and the lymphocyte-rich subtype being the least common. Further, the histological grade of HCC is determined according to the grading system of the WHO or the Edmonson and Steiner System. Through biopsies, HCC can be differentiated from intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma or metastases of other malignant tumors, especially metastases of the gastrointestinal tract. In summary, biopsies are fundamental in the diagnosis of HCC.

CT for estimating adequacy of lymph node dissection in patients with squamous cell carcinoma of the head and neck

Background Indices obtained from lymph node dissection specimens, specifically lymph node yield (LNY) and lymph node ratio (LNR), have prognostic significance in the setting of head and neck squamous cell carcinoma (HNSCCa). However, there are currently no validated tools to estimate adequacy of planned lymph node dissection using preoperative data. The present study sought to evaluate CT-derived estimates of lymphatic tissue volumes as a preoperative tool to guide cervical node dissection. Methods Fifteen cervical lymph node dissections were performed in 14 subjects with HNSCCa. Preoperative CT-derived estimates of lymphatic tissue volumes were compared with gross pathology tissue volume estimates and pathologically-determined LNY. Results Resected tissue volume (calculated using the triaxial ellipsoid method) correlates with CT-derived preoperative lymphatic volume estimates (r = 0.74, p = 0.003) while LNY does not(r = − 0.12, p = 0.67). When excluding pathologically enlarged lymph nodes (“refined” data), a negative correlation was observed between refined CT-derived volume estimates and refined LNY (r = − 0.65, p = 0.009). Conclusion In the setting of cervical lymph node dissection, CT-derived lymphatic volume estimates correlate with resected tissue volume, but refined CT-derived volume estimates correlate negatively with refined LNY. Trial registration Retrospectively registered. Level of evidence 4

EXTH-48. NOVEL COMBINATION THERAPY IN PRECLINICAL GLIOMA MODELS USING THE CELL CYCLE STABILIZING COMPOUND ARGYRIN F AND CHECKPOINT INHIBITION

Glioblastoma are incurable aggressive tumors and remain a therapeutic challenge. Glioblastoma frequently harbor alterations in the retinoblastoma pathway with subsequent cell cycle abnormalities. Here, we aimed to investigate the anti-glioma activity of the cell cycle-stabilizing compound Argyrin F and its potential treatment-induced vulnerabilities to exploit possibilities for novel combination therapies. We investigated cell viability, clonogenic survival, cell cycle status and immunoblots of human and murine glioma cells treated with Argyrin F. Moreover, we established an ex vivo glioma model using residual freshly resected tissue from patients, i.e. patient-derived microtumors (PDMs). Additionally, we extracted autologous tumor infiltrating lymphocytes (TILs) to perform co-culturing experiments. We performed mass spectrometry-based immunopeptidomics and used the orthotopic syngeneic SMA560/VM/Dk glioma mouse model. Argyrin F displayed anti-glioma efficacy in glioma cell lines in vitro and in PDM models ex vivo. Moreover, Argyrin F treatment induced cell cycle arrest, reduced clonogenic survival in vitro and prolonged survival in vivo. Argyrin F-treated SMA560 glioma displayed 4.6-fold more glioma-infiltrating CD8+ T cells. We discovered a distinctive treatment-induced immunopeptidome. Combination of Argyrin F plus PD-1 antibody increased cellular toxicity in PDM/TILs co-cultures ex vivo and prolonged overall survival compared with monotherapies in vivo. We conclude that our experimental data suggest a novel combination of Argyrin F plus PD-1 blockade and its clinical translation.

NIMG-28. PROSPECTIVE HISTOPATHOLOGY-VALIDATED MACHINE LEARNING FOR DISTINGUISHING TRUE PROGRESSION FROM TREATMENT-RELATED CHANGES IN GLIOBLASTOMA PATIENTS

PURPOSE Decision making about the best course of treatment for glioblastoma patients becomes challenging when a new enhancing lesion appears in the vicinity of the surgical bed on follow-up MRI (after maximal safe tumor resection and chemoradiation), raising concerns for tumor progression (TP). Literature indicates 30-50% of these new lesions describe primarily treatment-related changes (TRC). We hypothesize that quantitative analysis of specific and sensitive features extracted from multi-parametric MRI (mpMRI) via machine learning (ML) techniques may yield non-invasive imaging signatures that distinguish TP from TRC and facilitate better treatment personalization. METHODS We have generated an ML model on a retrospective cohort of 58 subjects, and prospectively evaluated on an independent cohort of 58 previously unseen patients who underwent second resection for suspicious recurrence and had availability of advanced mpMRI (T1, T1-Gd, T2, T2-FLAIR, DTI, DSC). The features selected by our retrospective model, representing principal components analysis of intensity distributions, morphological, statistical, and texture descriptors, were extracted from the mpMRI of the prospective cohort. Integration of these features revealed signatures distinguishing between TP, mixed response, and TRC. Independently, a board-certified neuropathologist evaluated the resected tissue by blindly classifying it in the above three categories, based on mitotic figures, pseudopalisading necrosis, geographic necrosis, dystrophic calcification, vascular changes, and Ki67. RESULTS Tissues classified as TRC by the neuropathologist were associated with imaging phenotypes of lower angiogenesis (DSC-derived features), lower cellularity (DTI-derived features), and higher water concentration (T2, T2-FLAIR features). Our ML model characterized TP with 78% accuracy (sensitivity:86%, specificity:70%, AUC:0.80 (95%CI, 0.68-0.92)) and TRC with 81% accuracy (sensitivity:80%, specificity:81%, AUC:0.87 (95%CI, 0.72-1.00)). CONCLUSION Our proposed ML model reveals distinct non-invasive markers of TP and TRC, directly associated with histopathological changes in prospective glioblastoma patients. Reliable stratification of TP and TRC entities may help to noninvasively determine whether the course of treatment should change.

Microcalcifications without a thyroid nodule as the sole sign of papillary thyroid carcinoma

Summary Our objective is to demonstrate the importance of considering microcalcifications even without evidence of nodules as a potential sign of malignancy. Current guidelines, such as those of the British Thyroid Association, acknowledge the clinical significance of microcalcifications only when found within nodules. In this case, they are considered a suspicious feature, classifying the nodules as U5 (i.e. high risk) where fine-needle aspiration biopsy (FNAB) is warranted, following the high likelihood of cancer in these nodules. In addition, there is a dearth of evidence of ultrasound scan (USS) detection of microcalcifications in the thyroid gland outside of nodules, along with their associated clinical implications. Yet, this clinical manifestation is not so infrequent considering that we do encounter patients in the clinic showing these findings upon ultrasound examination. Three patients who presented to our clinic with thyroid-related symptoms were shown to have areas of microcalcifications without a nodule upon sonographic evaluation of their thyroid gland. These incidentally detected hyperechoic foci were later confirmed to correspond to areas of papillary thyroid carcinoma (PTC) on histopathological examination of resected tissue following thyroidectomy. Four more cases were identified with sonographic evidence of microcalcifications without nodules and given their clinical and other sonographic characteristics were managed with active surveillance instead. Learning points Echogenic foci known as microcalcifications may be visible without apparent association to nodular structures. Microcalcifications without nodules may not be an infrequent finding. Microcalcifications are frequently indicative of malignancy within the thyroid gland even without a clearly delineated nodule. Empirically, the usual guidelines for the management of thyroid nodules can be applied to the management of microcalcifications not confined to a nodule, but such a finding per se should be classified as a ‘high-risk’ sign.

Management of parapharyngeal space cavernous sinus haemangioma using transoral robotic surgery

Cavernous haemangiomas are a very rare occurrence in the parapharyngeal space (PPS). Here, we present a case of a 58-year-old woman with an incidentally identified left PPS mass thought to be a pleomorphic adenoma that underwent excision by transoral robotic surgery (TORS). Intraoperative findings demonstrated no solid mass present and histological assessment of resected tissue confirmed a cavernous haemangioma. We discuss our experience in the management of a radiological and surgical mismatch of a PPS mass in what we believe to be the first cavernous haemangioma to be excised by TORS in this region.

Age-related changes in Tau and Autophagy in human brain in the absence of neurodegeneration

Tau becomes abnormally hyper-phosphorylated and aggregated in tauopathies like Alzheimers disease (AD). As age is the greatest risk factor for developing AD, it is important to understand how tau protein itself, and the pathways implicated in its turnover, change during aging. We investigated age-related changes in total and phosphorylated tau in brain samples from two cohorts of cognitively normal individuals spanning 19-74 years, without overt neurodegeneration. One cohort utilised resected tissue and the other used post-mortem tissue. Total soluble tau levels declined with age in both cohorts. Phosphorylated tau was undetectable in the post-mortem tissue but was clearly evident in the resected tissue and did not undergo significant age-related change. To ascertain if the decline in soluble tau was correlated with age-related changes in autophagy, three markers of autophagy were tested but only two appeared to increase with age and the third was unchanged. This implies that in individuals who do not develop neurodegeneration, there is an age-related reduction in soluble tau which could potentially be due to age-related changes in autophagy. Thus, to explore how an age-related increase in autophagy might influence tau-mediated dysfunctions in vivo, autophagy was enhanced in a Drosophila model and all age-related tau phenotypes were significantly ameliorated. These data shed light on age-related physiological changes in proteins implicated in AD and highlights the need to study pathways that may be responsible for these changes. It also demonstrates the therapeutic potential of interventions that upregulate turnover of aggregate-prone proteins during aging.

Visceral Mycotic Aneurysm: Superior Mesenteric Artery Aneurysm Caused by K. pneumoniae

We herein report a rare case of mycotic aneurysm of the superior mesenteric artery caused by <i>Klebsiella pneumoniae</i>. A 66-year-old man, a known case of hypertension and aorto-oesophageal fistula with stented aorta in 2010 and 2018, presented to the emergency department multiple times over 2 months with severe postprandial abdominal pain associated with vomiting and fever. On his last presentation, the obtained blood cultures grew ESBL positive <i>K. pneumoniae</i> and a repeated computed tomography (CT) showed a growing aneurysm at the origin of the ileocecal branch of the superior mesenteric artery measuring 17 × 10 mm (the aneurysm was 8 × 7.5 mm in the CT angiography on the previous admission). Extensive workup did not reveal the underlying cause of the mycotic aneurysm, thus we believe the cause to be the infected aortic stent, leading to bacteraemia and vegetations to the mesenteric artery causing the aneurysm. The management plan was placed by a multidisciplinary team consisting of vascular surgeons and infectious disease specialists along with review from a dietician to evaluate the patient’s nutritional status. The patient was started on total parenteral nutrition due to his postprandial pain and on antibiotic therapy according to the infectious disease team’s recommendation. He underwent surgical resection of the mycotic aneurysm, which showed a thrombosed aneurysm in the jejunoileal mesenteric area. The histopathology of the resected tissue demonstrated inflammatory aneurysm of the mesenteric artery. Following the surgery, the patient continued his antibiotic therapy and was discharged on the 13th post-operative day with follow-up appointments in the vascular surgery and infectious disease clinic.

Minimally invasive spinal surgery in a young cat with vertebral hypertrophy

Case summary A 2-year-old neutered female Scottish Fold cat was presented with an 8-week history of progressive back pain, paraparesis and decrease of postural reactions in both pelvic limbs. MRI showed spinal cord compression from both ventral sides, which originated from the T4 vertebral body and pedicle. The lesion compressing the spinal cord had a bone-like density on CT, and endoscopic surgery was performed to excise it. Histopathological examination of the resected tissue showed no evidence of malignancy and the lesion was diagnosed as vertebral hypertrophy. After surgery, the neurological status of the cat gradually improved. The cat was ambulant at the follow-up evaluation 2 weeks after surgery. Six months later, hindlimb paresis had improved considerably, and no recurrence was observed on CT. Relevance and novel information This is the first description of thoracic vertebral canal stenosis due to hypertrophy of a single vertebra in a young cat. Excision of the hypertrophic vertebra by endoscopic surgery is less invasive than open surgery and may give a good prognosis.

Use of Polarized Light in the Diagnosis of “Fuzz” Granuloma in the Conjunctiva of a Child

Synthetic fiber granulomas, also known as “Teddy Bear” granulomas or “Fuzz Ball granulomas,” are usually seen in childhood. We present a case of a 5-year-old child with a “Fuzz Ball” granuloma of the conjunctiva. The resected specimen was processed routinely. The use of polarized light during microscopic examination of the resected tissue made the diagnosis evident due to the prominent birefringence of the synthetic foreign material fibers.