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Lung adenocarcinoma metastatic to the ovary is rarely detected in clinical practice, and only a few cases have been reported. Its clinicopathological features, molecular genetics, and prognosis have not been well characterised. The data of 17 patients diagnosed with this disease between 2013 and 2022 were analysed retrospectively. All patients were non-smokers, with a median age of 46 years (range 30-71 years). Unilateral ovarian involvement was more frequent than bilateral involvement (58.8% vs 41.2%). Lesions presented as solid ovarian or mixed cystic and solid masses, and nearly two-thirds of the tumours (11/17, 64.7%) had a diameter greater than 10 cm. Solid adenocarcinoma was the most common histological subtype (9/17, 52.9%), and three of the cases showed abundant intracellular mucin and signet ring cells. Acinar adenocarcinoma was the second most common type (6/17, 35.3%), usually of moderate to poor differentiation. The remaining two cases were identified as micropapillary adenocarcinoma and mucinous adenocarcinoma. Multinodular growth, necrosis, and lymphovascular invasion were observed in half of the cases, and most of them had a marked stromal response. The most prevalent molecular alteration was ALK-rearranged (8/17, 47.1%), followed by EGFR gene mutations (5/17, 29.4%). A total of 34 cases, comprising 17 from the cohort and 17 from the literature, were included in the survival analysis. Patients with ALK-rearranged genes demonstrated an 80.0% 2-year overall survival rate, whereas those without ALK rearrangement exhibited a lower rate of 33.7%. Although there appears to be a potentially better prognosis for patients with ALK-rearranged genes, further cases and an extended follow-up period are necessary to substantiate this observation.

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INTRODUCTION: Claudin-4 has been described as a highly sensitive immunocytochemical marker for detection of metastatic carcinoma cells in effusion cytology specimens. This study aims to challenge the performance of claudin-4 in different types of malignancies and low cellularity specimens, by comparison with other markers in a large cohort of carcinomatous effusion specimens. METHODOLOGY: Cell block preparations from peritoneal and pleural fluid specimens were retrieved, with malignant (carcinoma) diagnoses confirmed by review of hospital diagnosis code and pathology reports. Claudin-4, BerEP4, CEA, and MOC31 immunocytochemistry were performed and scored by expression proportion and intensity. Tumor cellularity was assessed for subgroup analysis of low cellularity specimens. RESULTS: Totally 147 specimens (70 pleural, 77 peritoneal) of 68 lung, 62 breast, 9 gynecological, and 7 gastrointestinal carcinomas were retrieved. The average proportion expression of claudin-4 was highest (89.6%, vs. CEA 40.5%, BerEp4 18.6%, MOC31 16.8%) and the percentage of strong expression was highest for claudin-4 (72.1%). Expression levels of claudin-4 were consistently higher than other markers in subgroups of all primary sites. The difference was more significant for low cellularity specimens. High (≥50%) proportion expression was seen for 96.61% of cases for claudin-4 (vs. BerEp4 8.77%, CEA 46.55%, MOC31 8.77%, p < 0.001). These factors contributed to a low concordance between claudin-4 and BerEp4, CEA and MOC31 (K = 0.010-0.043). CONCLUSION: Claudin-4 is more sensitive than CEA, BerEp4 and MOC31, suitable for low cellularity specimens of most types of metastatic carcinoma and is a robust immunocytochemical marker for carcinoma that can be used solitarily.

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INTRODUCTION AND IMPORTANCE: Hand metastases are notably rare, comprising around 0.1% of all metastatic diseases, mainly originating from lung cancer, which is responsible for 30-40% of such cases. This report highlights a rare occurrence of distal phalangeal metastasis in a patient with Lynch syndrome, underscoring the diagnostic challenges associated with hand metastases. CASE PRESENTATION: A 70-year-old male diagnosed with Lynch syndrome 35 years ago, following colon adenocarcinoma, presented with severe inflammatory lesions on his right index finger. Patient had previous liver segmentectomies to remove metastatic lesions and had multiple cutaneous squamous cell carcinomas in various regions. Recent diagnostics, including a chest CT, identified a thoracic mass suggestive of squamous cell lung carcinoma. Histopathological analysis confirmed the metastasis of lung cancer to the index finger, necessitating a transphalangeal amputation. CLINICAL DISCUSSION: Hand metastases are extremely infrequent, often mimicking other conditions and requiring a high index of suspicion for accurate diagnosis. This case reinforces the lung as a frequent origin of hand metastases and the significance of elevated EGFR expression in facilitating metastatic spread. CONCLUSION: The rarity of hand metastasis in patients with genetic predispositions like Lynch syndrome calls for heightened vigilance and an integrated management approach. It highlights the critical role of histopathology in diagnosis and the need to consider genetic factors in treatment planning. Further research is encouraged to understand the mechanisms enabling certain cancers to metastasize to the hand and the role of genetic conditions in these processes.

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Ascites cytology is a cost-effective test for metastatic colorectal cancer (CRC) in the abdominal cavity. However, metastatic carcinoma of the peritoneum is difficult to diagnose based on biopsy findings, and ascitic aspiration cytology has a low sensitivity and specificity and a high inter-observer variability. The aim of the present study was to apply artificial intelligence (AI) to classify benign and malignant cells in ascites cytology patch images of metastatic CRC using a deep convolutional neural network. Datasets were collected from The OPEN AI Dataset Project, a nationwide cytology dataset for AI research. The numbers of patch images used for training, validation, and testing were 56,560, 7068, and 6534, respectively. We evaluated 1041 patch images of benign and metastatic CRC in the ascitic fluid to compare the performance of pathologists and an AI algorithm, and to examine whether the diagnostic accuracy of pathologists improved with the assistance of AI. This AI method showed an accuracy, a sensitivity, and a specificity of 93.74%, 87.76%, and 99.75%, respectively, for the differential diagnosis of malignant and benign ascites. The diagnostic accuracy and sensitivity of the pathologist with the assistance of the proposed AI method increased from 86.8% to 90.5% and from 73.3% to 79.3%, respectively. The proposed deep learning method may assist pathologists with different levels of experience in diagnosing metastatic CRC cells of ascites.

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Subglottic masses is very rare. The clinical data of five cases of subglottic mass in our hospital from 2017 to 2022 were summarized, and their clinical manifestations, auxiliary examination findings, treatment plan and pathological features were analyzed. Among the 5 patients, 1 case was subglottic pleomorphic adenoma, 1 case was subglottic granuloma, 1 case was subglottic breast cancer metastasis, 1 case was subglottic primary adenoid cystic carcinoma, and 1 case was immunoglobulin G4-related disease. No recurrence was observed in the patients so far. Subglottic mass is easy to be missed. Therefore, when the lesion is suspected in this area, the examination of ear, nose and throat should be carried out systematically to detect the lesion early and improve the prognosis.

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Breast sarcomatoid carcinoma, which are malignant tumors that form from the mesenchymal tissue of the mammary gland, are extremely uncommon and come in two varieties: primary and secondary (development associated to therapy). Breast sarcomas are malignancies that are aggressive and have a bad prognosis. Multidisciplinary surgery, chemotherapy, and radiotherapy are among the treatment possibilities. This case report reports a case of 35-year-old female presented to our hospital with a palpable tumor in her right breast and pungent discharge from her nipples. These signs persisted for over five years. A sarcomatoid breast cancer was discovered by postoperative histology.

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Acute appendicitis is the most common cause of abdominal pain that requires surgery. Appendiceal cancer is rare, comprising nearly 4% of all gastrointestinal diagnoses. It is common to find neuroendocrine neoplasms due to metastasis in this site. Appendix tumors are usually asymptomatic; however, if they are advanced or have metastases, they can cause abdominal symptoms. Computed tomography (CT) is commonly used to diagnose acute appendicitis in these cases. CT usually shows an increased appendiceal diameter with thickening (>3 mm) of the appendiceal wall, an intraluminal fluid depth >2.6 mm, and periappendiceal inflammation. Histopathological findings confirm the diagnosis. Medical and surgical management depends on physical characteristics such as size, location, and degree of evolution. We present the case of a 77-year-old woman with a family history of well-controlled type 2 diabetes mellitus and hypertension. She was referred to our institution after four days of abdominal pain in the epigastrium and both flanks accompanied by fever. An abdominal CT showed left pleural effusion and appendicular thickening. Laboratory tests showed high blood glucose levels, leukocytosis at the expense of neutrophils, an increased platelet count, and decreased albumin and total proteins. The CT scan also showed a calcified granuloma in the anterior segment of the right upper lobe and an irregular image with partially defined hypodense borders in the liver in segment IVb. We report our experience with the diagnosis, management, and treatment decisions of this case. It is important to mention that the first diagnosis was acute appendicitis. This diagnosis motivated us to seek other symptoms and signs by direct questioning and imaging studies leading us to diagnose metastatic lung cancer.

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BACKGROUND: We present an unusual case of a left axillary lymph node metastasis from a primary dedifferentiated endometrial carcinoma. This pattern of metastasis is likely the result of circulating tumor cells reaching the node through its arterial blood supply. CASE PRESENTATION: In this report, a 68-year-old white woman with a dedifferentiated endometrial carcinoma underwent a hysterectomy. She later developed an enlarged axillary lymph node due to metastatic dedifferentiated endometrial carcinoma, treated with chemotherapy and anti-programmed cell death protein 1 immunotherapy resulting in a complete clinical and radiological response. CONCLUSION: A review of the literature reveals the rarity of blood-borne lymph node metastasis, especially with uterine carcinoma. Immunotherapy has shown promising results in the treatment of some subtypes of metastatic uterine carcinoma.

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BACKGROUND: The supraclavicular lymph node (SCN) is a common metastatic site for malignancies of supra and infra-diaphragmatic origin and is easily accessible for small biopsy and fine needle aspiration (FNA). In this study, the utility of SCN biopsies was analyzed for diagnosis and ancillary studies. METHODS: The electronic pathology archive was searched for cases of FNA of SCNs accompanied by small core biopsies (1/2016-12/2018). The patients' demographics, diagnosis, and ancillary studies were recorded. RESULTS: Eighty-eight cases were reviewed (49 females and 39 males), with patients' ages ranging from 23 to 84 years (mean = 52.85 years). Fifty-four (61.4%) specimens were from the left SCN and thirty-four (38.6%) from the right. All FNA cases were performed by a radiologist under ultrasound guidance and rapid on-site evaltion (ROSE) was performed by a cytologist. Nineteen cases (21.6%) were benign and sixty-nine cases were malignant (78.4%). Carcinoma was the most common malignant neoplasm (52.3%) including 38.2% (13/34) of the right SCN and 61.1% (33/54) of the left SCN cases. Metastatic lung and breast adenocarcinomas (9.1% each) were the most common carcinomas overall. Lymphoma was the second most common malignancy (17.0%) including 17.6% (6/34) of the right SCN and 16.7% (9/54) of the left SCN cases. The majority of cases were accomponied by ancillary studies for diagnosis and prognostic markers. Ancillary studies included immunostains (63 cases, 71.6%), PD-L1 testing (21 cases, 23.9%), FISH testing (7 cases, 8.0%), flow cytometry (20 cases, 22.7%) and NGS studies (8 cases, 9.1%). CONCLUSION: Supraclavicular lymph nodes are easily accessible and diagnostically useful sites for detection of malignancies and molecular alterations responsive to targeted or immune therapy.

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BACKGROUND: Metastatic carcinoma of the thyroid gland is a rare encounter in clinical practice, but autopsy series showed that it is not so rare. Thyroid metastasis from colorectal cancer (CRC) is rare and has a poor prognosis. We herein report a rare case of solitary thyroid metastasis from rectal cancer combined with needle tract implantation after fine-needle aspiration (FNA) of the thyroid nodule and review the relevant literature. CASE SUMMARY: A 54-year-old woman with a history of TNM stage III CRC presented a 1.3 cm × 1.0 cm mass in the left thyroid gland. FNA and histological examination of the left thyroid lobe surgical specimen confirmed the diagnosis of isolated metastatic adenocarcinoma from the rectum. Needle tract implantation was observed in the neck 11 mo after the FNA examination. The 2.5-cm seeding lesion was successfully removed by surgery, and the patient recovered well. The literature relevant to this clinical condition, the diagnostic workup, spread pathway, and surgical management of these rare lesions is reviewed. CONCLUSION: For a patient with a thyroid mass and a history of CRC, metastatic thyroid carcinoma should be considered even if the patient has no evidence of other organ metastasis from CRC. FNA cytological examination of the thyroid mass is useful in the differential diagnosis between primary thyroid disease and metastatic thyroid carcinoma. Thyroid lobectomy of the gland containing the metastatic tumor is suggested in patients with metastatic carcinoma of the thyroid.

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Objective: The aim of this study was to evaluate the post-marketing safety, tolerability, immunogenicity and efficacy of Bevacizumab (manufactured by Hetero Biopharma) in a broader population of patients with solid tumors. Patients And Methods: This phase IV, prospective, multi-centric clinical study was carried out in Indian patients with solid malignancies (metastatic colorectal cancer, non-squamous non-small-cell lung cancer, metastatic renal cell carcinoma) treated with Bevacizumab between April 2018 and July 2019. This study included 203 patients from 16 tertiary care oncology centers across India for safety assessment, of which a subset of 115 patients who have consented were also evaluated for efficacy and immunogenicity. This study was prospectively registered in the Clinical Trial Registry of India (CTRI), and was commenced only after receiving approval from the competent authority (Central Drugs Standard Control Organization, CDSCO). Results: Out of the 203 enrolled patients, 121 (59.6%) patients reported 338 adverse events (AEs) during this study. Of 338 reported AEs, 14 serious adverse events (SAEs) were reported by 13 patients including 6 fatal SAEs, assessed as unrelated to the study medication and 7 non-fatal SAEs, 5 assessed as related, and 3 unrelated to Bevacizumab. Most AEs reported in this study (33.9%) were general disorders and administration site conditions, followed by gastrointestinal disorders (29.1%). The most frequently reported AEs were diarrhea (11.3%), asthenia (10.3%), headache (8.9%), pain (7.4%), vomiting (7.9%), and neutropenia (5.9%). At the end of the study, 2 (1.75%) of 69 patients reported antibodies to Bevacizumab without affecting safety and efficacy. However, at the end of 12 months, no patient had reported antibodies to Bevacizumab. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were reported in 18.3%, 22.6%, 9.6%, and 8.7% of patients, respectively. The overall response rate (CR + PR) was reported in 40.9% of patients at the end of the study. Disease control rate (DCR), also known as the clinical benefit rate (CBR) was reported in 50.4% of patients. Conclusions: Bevacizumab (Cizumab, Hetero Biopharma) was observed to be safe, well tolerated, lacking immunogenicity, and efficacious in the treatment of solid tumors. The findings of this phase IV study of Bevacizumab, primarily as a combination therapy regimen suggest its suitability and rationality for usage in multiple solid malignancies. Clinical Trial Registry Number: CTRI/2018/4/13371 [Registered on CTRI http://ctri.nic.in/Clinicaltrials/advsearch.php : 19/04/2018]; Trial Registered Prospectively.

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The mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may spread to the human brain are poorly understood, and the infection of cancer cells in the brain by SARS-CoV-2 in Coronavirus disease 2019 (COVID-19) patients has been the subject of only one previous case report. Here, we report the detection of SARS-CoV-2 RNA by in situ hybridization in lung-cancer cells metastatic to the brain and adjacent brain parenchyma in a 63-year-old male patient with COVID-19. These findings suggest that metastatic tumors may transport the virus from other parts of the body to the brain or may break down the blood-brain barrier to allow for the virus to spread to the brain. These findings confirm and extend previous observations that cancer cells in the brain can become infected by SARS-CoV-2 in patients with COVID-19 and raise the possibility that SARS-CoV-2 can have a direct effect on cancer growth and outcome.

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We present a case of a 68-year-old female with a history of hypertension and hypothyroidism who presented to the emergency department with right lower extremity pain and difficulty ambulating. An initial evaluation revealed an abnormal appearance of the right hip on MRI, concerning avascular necrosis versus acetabular compression fracture. Subsequent diagnostic procedures, including joint aspiration and radiologic bone biopsy, led to the surprising discovery of metastatic lung carcinoma on tissue pathology. Further work-up reveals lung primary adenocarcinoma with additional metastases to the brain as well. The patient underwent resection of acetabulum and complex surgical pelvis reconstruction, irradiation for brain metastases, and rehabilitation. This case highlights the importance of considering atypical presentations of metastatic malignancies and the need for a multidisciplinary approach to optimize patient management.

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Currently, there is a paucity of highly specific and sensitive markers to identify breast carcinoma in male patients. Immunohistochemical stains commonly used for unmasking primary breast carcinomas include estrogen receptor (ER) and GATA3. However, these markers are commonly expressed in carcinomas originating from other organ systems and can be reduced in breast carcinomas with higher histologic grades. Androgen receptor (AR) may be used to highlight primary male breast cancer, but this marker can also be expressed in other carcinomas. We evaluated TRPS1, a highly sensitive and specific marker for female breast carcinoma, in cases of male breast carcinoma. Through an institutional database search, we identified 72 cases of primary invasive breast carcinoma in male patients. Among ER/progesterone receptor (PR)-positive cancers, 97% showed intermediate or high positivity for both TRPS1 and GATA3. Among HER2-positive cancers, 100% showed intermediate or high positivity for TRPS1 and GATA3. One case of triple-negative breast cancer was collected, showing high positivity for TRPS1 and negativity for GATA3. AR staining was non-specific and heterogeneous: 76% showed high positivity, but the remaining 24% showed low or intermediate positivity. Additionally, among 29 cases of metastatic carcinoma to male breast tissue, 93% were negative for TRPS1, and the remaining 2 cases (7%), which were carcinomas from salivary gland primary tumors, were intermediate positive. TRPS1 is a sensitive and specific marker in the unmasking of male primary invasive breast carcinoma across different subtypes. Additionally, TRPS1 is not expressed in metastatic carcinomas of multiple primaries, with the exception of salivary gland primaries.

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Extramedullary hematopoiesis (EMH) is a rare complication of solid tumor malignancies. We describe the first case of a patient who developed EMH in the pericardium secondary to metastatic gastrointestinal or pancreaticobiliary cancer. A 58-year-old man presented with recurrent episodes of fatigue and shortness of breath and was treated with thoracocentesis and pericardiocentesis for pleural and pericardial effusions, respectively. Owing to a markedly elevated alkaline phosphatase, a bone scan was performed and demonstrated diffuse sclerotic lesions. Evaluation of pleural effusion diagnosed metastatic adenocarcinoma, and cytospin morphology of the pericardial fluid demonstrated EMH. While EMH secondary to solid tumors is commonly suggested to be due to cytokine signaling, we propose the mechanism of EMH in this patient was due to extensive disruption of bone marrow hematopoiesis, similar to what is seen in myeloproliferative neoplasms.

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Ancillary tests are commonly used in the surgical pathology setting for diagnosing challenging neoplastic diseases of the liver and biliary tract, while histology and clinical correlation remain to be critically important. With continuous discoveries, more and more useful ancillary tests have become available, which can help distinguish between malignant and benign hepatocellular neoplasms, malignant and benign biliary tract entities, and intrahepatic and metastatic carcinomas. This review will focus on existing and emerging biomarkers (such as glutamine synthetase, organic anion transporting polypeptide 1B3, insulin-like growth factor-II mRNA binding protein-3, S100P, SMAD4, enhancer of zeste homolog 2, albumin, hepatocyte nuclear factor-1ß, etc.) that can be used for the diagnosis, classification and prognostication of hepatobiliary neoplasms.

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INTRODUCTION: Malignant serous effusions are common in metastatic carcinomas. Although cytomorphology is recognized as the gold standard diagnostic method, it exhibits moderate sensitivity. This study aimed to assess the diagnostic value of immunophenotyping with a single epithelial marker, known as the epithelial cell adhesion molecule (EpCAM, CD326), in discriminating malignant metastatic carcinomas of serous fluids. METHODS: This prospective study was conducted on suspicious or confirmed cases of malignant tumors from September 16, 2019, to June 21, 2020. Serous fluid samples were assessed via cytomorphology using the Wright-Papanicolaou method and the anti-EpCAM mouse monoclonal antibody (clone VU-1D9) flow cytometry. The EpCAM(+)/CD45(-) immunophenotype was defined as the metastatic involvement of carcinoma in the serous cavity. RESULTS: A total of 118 samples (90 females and 28 males; mean age, 54.04 ± 16.14 years), collected from peritoneal and pleural fluids, were examined in this study. Five samples (4.24%) were positive in both EpCAM flow cytometry and cytology, while 102 samples (86.44%) were negative for both EpCAM flow cytometry and cytology, yielding an overall agreement of 92%, 84%, and 90.7% for the peritoneal, pleural, and total samples, respectively. Based on the Bayesian latent class model, the EpCAM flow cytometry showed sensitivity and specificity of 58.5% (95% CI: 0.3, 99.7) and 96.2% (95% CI: 47.8, 100), respectively. The corresponding values were 68.7% (95% CI: 0.3, 99.9) and 96.1% (95% CI: 47, 100) for cytology, respectively. CONCLUSION: The EpCAM flow cytometry and cytology showed comparable performance in detecting metastatic effusions. The EpCAM flow cytometry might have a diagnostic value in decreasing the false-negative rate of cytomorphology, while maintaining excellent specificity.

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BACKGROUND: Prostate cancer development and progression to androgen-independent disease is correlated with increased expression of growth factors and receptors capable of establishing autocrine and/or paracrine growth-stimulatory loops. Overexpression of the Her2/neu receptor tyrosine kinase has been associated with the progression to androgen independence in prostate cancer cells. OBJECTIVE: Our primary aim was to investigate the frequency of HER2/neu amplification in prostate biopsy specimens in newly diagnosed metastatic carcinoma prostate and its correlation to progression of androgen independent carcinoma. MATERIALS AND METHODS: In our study, expression of HER2/neu was carried out by immunohistochemical analysis in TRUS biopsy specimen of newly diagnosed metastatic carcinoma prostate. RESULTS: Out of 36 patients, seven (19.4%) showed her2neu overexpression on immunohistochemical staining. Five out of seven (71%) were associated with higher histological grade >7 at diagnosis (p < 0.05). Her2neu overexpression was not significantly associated with age and serum PSA at diagnosis. However progression to castration resistant stage was not dependant on Her2/neu status (p > 0.05). CONCLUSION: Overexpression of her2/neu was associated with high grade carcinoma prostate at diagnosis, however progression to castration resistant stage was not related with her2neu expression.

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