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A 68-year-old Chinese man was found to have a lobular mass in the sphenoid sinus which extended to the clivus and the roof of the nasopharynx on a staging MRI scan performed for his high-grade parotid salivary duct carcinoma. Further positron emission tomography scan showed that this lesion was fluorodeoxyglucose (FDG) avid. This proved to be a diagnostic dilemma. The patient underwent a total parotidectomy, left selective neck dissection and a transphenoidal biopsy of his nasal lesion. Final histology revealed that this lesion was a synchronous ectopic sphenoid sinus pituitary adenoma (ESSPA). Initial differential diagnoses that were considered included a chordoma, metastatic carcinoma and nasopharyngeal carcinoma. However, an important differential with a neoplastic appearance and a tendency for positive FDG uptake is an ESSPA. It requires dedicated immunohistochemical staining to diagnose, and its mainstay of treatment is surgical excision.

The 2019 WHO classification recognizes two morphologic variants of cholangiocarcinoma: 1) small duct type, and, 2) large duct type; the former is associated with IDH1/2 mutations and FGFR2 fusions. Therapies targeting these genetic alterations have recently been approved by the FDA. The liver is a favored site of metastasis in the body, and it is thus imperative to distinguish metastatic adenocarcinoma from cholangiocarcinoma. The traditional diagnostic approach employs immunohistochemical stains to exclude a metastatic carcinoma. Cholangiocarcinoma has been considered a diagnosis of exclusion and extensive clinical and imaging work-up has been necessary before this diagnosis can be made. The presence of cholangiolar pattern and positive albumin on in situ hybridization favor a diagnosis of cholangiocarcinoma. This review aims to update the reader on the new morphologic classification, and diagnostic and molecular advances in cholangiocarcinoma.

Background: Advances in systemic cancer therapies have improved survival for patients with metastatic carcinoma; however, it is unknown whether these advances have translated to improved survival for patients with appendicular metastatic bone disease (A-MBD) after orthopedic interventions. We conducted a study to evaluate the trend in overall survival for patients who underwent orthopedic surgery for A-MBD between 1968 and 2018. Methods: A systematic search of Embase and Medline to identify studies published since 1968 evaluating patients treated with orthopedic surgery for A-MBD was conducted for a previously published scoping review. We used a meta-regression model to assess the longitudinal trends in 1-, 2- and 5-year overall survival between 1968 and 2018. The midpoint year of patient inclusion for each study was used for analysis. We categorized primary tumour types into a tumour severity score according to prognosis for a further meta-regression analysis. Results: Of the 5747 studies identified, 103 were retained for analysis. Meta-regression analysis showed no significant effect of midpoint study year on survival across all time points. There was no effect of the weighted average of tumour severity scores for each study on 1-year survival over time. Conclusion: There was no significant improvement in overall survival between 1968 and 2018 for patients with A-MBD who underwent orthopedic surgery. Orthopedic intervention remains a poor prognostic variable for patients with MBD. This finding highlights the need for improved collection of prospective data in this population to identify patients with favourable survival outcomes who may benefit from personalized oncologic surgical interventions.

Anaplastic lymphoma kinase positive large B-cell lymphoma (ALK+LBCL) is a rare subtype of B-cell lymphoma with aggressive features and a poor prognosis. The rarity of this disease and similarity of microscopic features with undifferentiated epithelial neoplasm disturb the provision of proper treatment. A 57-year-old male presented with a rapidly growing and painless mass on the left side of the neck. Metastatic carcinoma of an unknown primary (CUP) lesion was initially suspected based on the pathologic results obtained from a core needle biopsy, but it was finally diagnosed as ALK+LBCL after a modified radical neck dissection. We herein report a case of ALK+LBCL mimicking CUP with a literature review.

Surgical treatment of patients with postoperative ventral hernias is one of the most pressing problems in herniology. Verification of the diagnosis of postoperative ventral hernia is usually not difficult. At the same time, there may be difficulties in diagnosis associated with determining the true size of the hernia orifices, the contents of the hernial sac. These moments are determined by various factors: the location of the hernia on the anterior abdominal wall, the age, sex of the patient, as well as anamnesis of hernia and the volume of surgery previously performed. One of the very rare situations in external abdominal hernias is the situation when the content of the hernial sac is the part of the parenchymal organ, the tumor process, as well as foreign bodies. The study presents the observation materials of three patients admitted for diagnosis and treatment to the surgical hospital clinics of Irkutsk State Medical University. When examined and treated, it was found that in one case the content of the hernia sac included a part of the left lobe of the liver, in another observation, the inguinal hernia sac contained metastatic carcinoma, in the third case – a foreign body was found. All patients underwent surgery (hernioplasty, hernioplasty). Diagnosis of hernia of the anterior abdominal wall was confirmed. A literary search was made for rare clinical examples in herniology. In the world literature, there are only eight observations when the content of the hernia sac was a part of the lobe of the liver; the presence of metastatic carcinoma and a free foreign body we found as single observations described by known specialists in herniology.

Bowel obstruction is a frequently encountered condition worldwide that causes numerous admissions to hospitals. Metastatic carcinoma has been identified as one of the infrequently encountered causes of bowel obstruction. Prostate cancer typically metastasizes to lymph nodes, bone, lungs, liver, and brain. In this article, we reported the case of a 75-year-old man who presented with bowel obstruction due to narrowing and stricture of the rectum. Primary rectal mass was initially diagnosed, but upon further investigation, it was found that the mass resembled prostate tissue. The bowel obstruction was managed surgically with a colostomy. The patient was later referred to oncology for chemotherapy and hormonal therapy.

A 5-year-old male castrated Domestic Shorthair cat was presented to a veterinary specialty hospital for evaluation of large-volume pleural effusion. Echocardiography revealed a large intracardiac mass at the level of the interatrial septum impairing right atrial inflow resulting in lymphocytic pleural effusion and ascites. Differential diagnoses included lymphoma, hemangiosarcoma, rhabdomyosarcoma, chemodectoma, neurofibrosarcoma, myxoma, metastatic carcinoma or intracardiac thrombus, abscess or granuloma. Due to poor long-term prognosis and recurrent, large-volume pleural effusion, the cat was humanely euthanized. The heart was submitted for histopathologic evaluation. The mass was subsequently determined to be a malignant extra-adrenal nonchromaffin paraganglioma (chemodectoma) arising from the pulmonary trunk near its bifurcation in the region of the glomus pulmonale. Chemodectomas are rare in cats and to the authors' knowledge, there are no reports of one originating from the glomus pulmonale.

Background: Due to their low prevalence and variable clinical presentation, oral metastatic tumours present a diagnostic challenge to the clinician. This case describes the presentation of a mandibular metastatic tumour in an apparently healthy patient, initially managed as dento-alveolar infection by her general dental practitioner (GDP). Case description: A 56-year-old female attended her GDP with a small intraoral swelling buccal and lingual to the lower left incisors, canine and first premolar. Radiographic examination revealed gross caries in the lower left anterior dentition and periapical bone loss in the region. A week's course of antibiotics had no effect. The swelling increased rapidly and the involved teeth were extracted by the GDP before referral to Oral Surgery. The patient offered no history of weight loss, febrility or breathlessness. Her medical history was unremarkable. She smoked and did not consume alcohol. Histological examination revealed a poorly differentiated metastatic carcinoma. A computerized tomography scan of the neck showed a 4 cm mass in the left anterior mandible with adjacent bony destruction. There was bilateral cervical lymphadenopathy and a large right-sided upper lobe lung mass with metastasis to the contralateral upper lobe of the lung, the right adrenal gland and brain. A diagnosis of poorly differentiated non-small cell carcinoma of the lung was made, staged T4 N3 M1c. Nine weeks after her initial presentation to the GDP, the patient suffered a seizure and passed away. Conclusion: This case demonstrates an uncommon presentation of mandibular metastatic tumour as the first indicator of advanced malignant disease. The presentation of such tumours can often mimic more common, benign processes, making diagnosis challenging. At a time of increased remote assessment of patients due to the COVID-19 pandemic, it is particularly important for clinicians to consider the possibility of malignancy when faced with any unusual case of swelling. © 2021 British Association of Oral Surgeons and John Wiley & Sons Ltd.

Objective Gliosarcomas (GS) comprise ~ 2 - 8% of glioblastomas and are associated with a similar poor prognosis. GS have rarely been found with a primitive neuroectodermal component (PNET). We present a case of gliosarcoma with PNET features (GS-PNET) that mimicked a neuroendocrine carcinoma on initial biopsy. Materials and methods A 68-year-old male presented with 2 weeks of increasing headaches and difficulties with reading, writing, and word-finding. He was found to have a left-sided parieto-occipital heterogeneously enhancing mass. Results Pathologic analysis after surgical resection initially diagnosed a poorly differentiated carcinoma with neuroendocrine features, and adjuvant therapy was guided by this diagnosis as well as systemic imaging, which was suggestive of gastrointestinal primary malignancy with central nervous system (CNS) metastasis. Subsequent progression and re-resection established a diagnosis of GS with PNET component. Genomic profiling showed shared PTEN, TERT promotor, and TP53 mutations in the original and recurrent tumors. Conclusion There have only been 5 previously reported cases of GS-PNET, to our knowledge, with this case representing the first with comprehensive molecular profiling. The case also highlights the importance of further work-up of presumed metastatic carcinoma with indeterminate immunostaining and/or suspected non-epithelioid component.

Distal femoral endoprosthetic replacement has been successfully used to reconstruct distal femoral defects after tumor resection for over four decades. Despite continued advances, aseptic loosening continues to be the most common failure mode after infection. Debate still exists about a variety of design features and the optimal fixation method remains controversial. To date, no large-scale study or meta-analysis has demonstrated the superiority of one fixation technique over another. While the classic dichotomy of cemented versus cementless stems is well-known, the contemporary surgeon needs to fully understand the optimal clinical setting for each type of fixation technique and additional strategies to maximize implant stability. In clinical practice, the choice of fixation must be tailored to the individual patient. The surgeon must consider whether the operation is being performed for primary sarcoma or metastatic carcinoma, the presence of distant metastases, age, comorbidities, and whether radiotherapy has been previously given or will be required at the site of fixation. The best strategy for each patient optimizes tumor control and appropriately weighs risks of fixation failure versus the expected patient survival. This review will explore cemented and uncemented distal femoral replacement and highlight modern concepts to optimize each technique.

Background Krukenberg tumors are uncommon and are indicative of an ovarian metastatic carcinoma that originates from another site of primary malignancy. The majority of metastases to ovaries are derived from the stomach and colon. We present a rare case of a metastatic ovarian malignant tumor that originated from gallbladder adenocarcinoma. Case presentation A 45-year-old premenopausal Korean woman presented with abdominal distension. Bilateral multiseptated ovarian tumors and a wall-thickened gallbladder were found on abdominal computed tomography. The patient was diagnosed with metastatic ovarian carcinoma arising from gallbladder adenocarcinoma and was treated with adjuvant chemotherapy. Conclusions Metastases to the ovaries from other sites, including the gallbladder, are rare and usually resemble primary ovarian tumors. Therefore, potential metastatic ovarian tumors of newly diagnosed pelvic masses should be considered in differential diagnoses.

Background Axillary lymph node (ALN) ultrasound-guided fine needle aspiration biopsy (US-FNAB), a minimally invasive procedure, may be used for the preoperative evaluation of ALN status of breast cancer patients. Despite the relative ease of use and low cost, paucity of comparative studies and variation in the reported sensitivity of FNAB preclude its clinical utility in evaluation of ALNs. This study aims to determine the accuracy of US-FNAB in detecting metastasis in ALN pre-operatively and to assess US-FNAB as a viable alternative to sentinel lymph node (SLN) excision. Methods The 228 consecutive ALN US-FNABs with subsequent histologic follow up performed from 2005 to 2020 in patients with breast carcinoma were retrospectively evaluated. FNAB results were correlated with histologic diagnosis. Sensitivity, specificity, accuracy, and risk of malignancy of FNAB were calculated. Results 157/228 (69%) FNABs were concordant with histology, 37/228 (16%) discordant. Positive FNAB findings correlated with primary tumor size, grade, number of metastatic lymph nodes and size of metastases. FNAB with negative diagnosis carried a 22% risk of malignancy, atypical 43%, suspicious 80%, and positive a 100% risk of malignancy (100% positive predictive value [PPV]). The sensitivity and specificity were 78% and 95% respectively; accuracy was 77%. SLN biopsy was avoided in all 82 (36%) cases with positive FNAB results. Conclusion Negative FNAB result does not exclude metastatic carcinoma. With 100% PPV, full ALN dissection and/or neoadjuvant chemotherapy can be safely planned after a positive FNAB result, avoiding SLN biopsy, reducing management costs and shortening time interval to definitive therapy.

Purpose: To describe the primary tumour type, clinical features, treatment and outcome of patients with Iris metastasis.Methods: Retrospectively analyzed articles published from 1934 to 2019 in the PubMed database.Results: In total, 133 eyes of 125 patients with iris metastatic carcinoma were retrieved. The average age at metastasis diagnosis of the patients was 56 ± 15 years; 60 left eyes and 49 right eyes were involved. The most common primary tumors were lung carcinoma (42%) and breast carcinoma (15%). Approximately one-third of the patients were first diagnosed in the ophthalmology department before the primary tumor was detected. Twenty-two percent of iris metastases were discovered before and 33% were discovered after systemic metastasis. The most common complaints were blurred vision and pain. The clinical features included iris masses, neovascularization and keratic precipitates. 57 patients (64%, N = 90) had an elevated intraocular pressure. Local administration of radiation therapy or intraocular injections of anti-VEGF drugs relieved eye discomfort and controlled the high intraocular pressures.Conclusions: Iris nodules with increased intraocular pressure and neovascularization may indicate iris metastasis. Lung cancer is the most common primary tumor.

Background & Objective: Liver lesions are difficult to diagnose and to differentiate primary from metastatic carcinoma, while Biopsy has its limitations. Cell block technology is easily accessible with high diagnostic accuracy. Our aim is 1) To find the role of cell block technology as an alternative to biopsy in identifying liver lesions; 2) To find the efficacy of cell block along with immunohistochemistry (IHC) and ancillary studies in differentiating primary from metastatic lesions; 3) To identify the site of origin of metastatic lesions. This is a descriptive study undertaken in two tertiary care hospitals over a period of three years. Methods: Retrospective review of adequate samples from fine needle aspirations from liver lesions under radiological coverage, converted into cell block was done. IHC was applied as needed. Usefulness of cell block preparation was evaluated, and the final diagnosis correlated with the biopsy results. Results: Analysis of 323 cases found sensitivity of 98.75% and positive predictive value of 99% for all lesions. Sensitivity for metastatic carcinomas was slightly more than hepatocellular carcinoma. However, accuracy of cell block results for individual metastatic lesions and site of origin was less. IHC and morphological pattern worked as an important adjunct in the final diagnosis. On the other hand, contribution of viral markers as a supplement in the final work up was ambiguous. Conclusion: High precision of validity results of cell block technology in comparison with biopsy highlights its pivotal role in conjunction with supportive tests for diagnosing and differentiating liver lesions as well as identifying primary sites in liver metastasis.

Leptomeningeal carcinomatosis (LC) is defined as infiltration of the leptomeninges by metastatic carcinoma and often represents the end stage of cancer disease. In breast cancer, LC is associated with a median survival of approximately 6-8 weeks without specific treatment. It could increase by only few months with personalized treatment plans. Usually, the median time of onset of leptomeningeal spread is 18 months and it is diagnosed in up to 70% of patients with active and progressive systemic disease. We present an uncommon case of LC in a patient with history of breast cancer with a 10 year-disease-free condition and an overall survival after LC diagnosis of 10 months. Central Nervous System (CNS) Magnetic Resonance Imaging (MRI) showed contrast enhancement of medullary cone and cauda. Despite the negativity of cytological analysis of Cerebral-Spinal Fluid (CSF), the patient underwent meningeal and radicular biopsy in November 2019. The neuropathological examination confirmed the diagnosis of LC. The patient was started on the aromatase inhibitor anastrozole. A whole body contrast Computed Tomography (CT) scan at three months follow-up was negative for further disease dissemination. The patient is currently under oncological and radiological follow-up after more than 10 months from diagnosis. Although nowadays diagnosis of LC is prompted by cytological examination of CSF, its negativity should not halt the diagnostic process. In the presence of a high clinical suspicion of LC, we suggest the biopsy of lesion.

Thyroid metastatic cancer is rare. It may be ignored due to the longer course of the primary disease and the less obvious symptoms. With the popularity of ultrasonography, it can help the early detection of thyroid metastatic cancer. In this case, a 50-year-old woman was diagnosed with thyroid metastasis due to a "decade of lung cancer". The main clinical manifestation of the patient was that although the thyroid area was not enlarged, the texture was stiff. Unlike common thyroid cancer, this patient did not experience hoarseness. The patient underwent ultrasound-guided biopsy of the thyroid area and examined the pathological section. Unlike previous ultrasound manifestations of common thyroid metastatic cancer, the ultrasound results in this case were shown as diffuse, point-like hyperechoic. Ultrasound-guided biopsy of the thyroid site was performed on the patient, and pathological sections were examined. The obtained thyroid pathology section results are shown that metastases of poorly differentiated cancers, tending to adenocarcinoma, considering metastasis in combination with history. The treatment used by this patient was taking thyroxine tablets, but the efficacy was not satisfactory. Early diagnosis of metastatic cancer provides feasible help, and ultrasound-guided puncture biopsy may be used to further diagnose metastatic thyroid cancer if necessary.

Introduction Second primary nonlymphoid malignancies (SPNLM) have long been recognized as a complication of chronic lymphocytic leukemia (CLL). Materials and methods A search was made of our cytopathology database for cases of CLL that also contained a SPNLM. Results Seventeen cases from 13 known CLL patients [M:F = 2.3:1; age range: 47-77 years, x = 67 years] met criteria for this study. SPNLMs consisted of different forms of metastatic carcinoma (10 patients) and malignant melanoma (3). Of 16 FNA biopsies and 1 pleural fluid, 82% had ancillary testing; 35% had the specimen subdivided for both flow cytometry (FCM) and immunohistochemistry (IHC). Lymph node was the most common site for FNA biopsy (12), followed by face (2), and soft tissue (2). Squamous cell carcinoma was the most common SPNLM (6), followed by melanoma (3), and there were single cases of adenocarcinoma, large cell neuroendocrine carcinoma, Merkel cell carcinoma, and papillary thyroid carcinoma. A correct specific cytologic diagnosis was made in 15 (88%) cases. Conclusions Cytopathology is highly proficient in recognizing SPNLM in CLL patients. Utilization of cytologic material for FCM and IHC is feasible, and extremely helpful in achieving diagnostic accuracy.

Rapidly growing, symptomatic, non-hematological, malignant neck masses are unusual in young adults. We report a case of a 34-year-old African American male with sickle cell trait who presented with a large left supraclavicular/cervical mass comprising of poorly differentiated malignant epithelial cells consistent with metastatic carcinoma of unknown origin. Upon immunohistochemistry, the tumor showed loss of INI1 (BAF47) and retained PAX-8 expression. After extensive clinical and radiological work-up the primary tumor was found to be a 2.6 cm renal medullary carcinoma. This case highlights the role of multidisciplinary approach to the diagnosis of a neck mass and to understanding that certain genetically-defined tumors can occur at and metastasize to any site.

High-grade serous carcinoma (HGSC) of ovary is the commonest of all ovarian malignant tumours and is associated with high mortality rate. Serous tubal intraepithelial carcinoma (STIC) is believed to be the precursor lesion. In literature, only 40-50% of HGSC shows concurrent STIC, even after thorough sampling. We, herein, present a case of a 40-year female, who underwent staging laparotomy for bilateral ovarian carcinoma. She was diagnosed as HGSC of both ovaries. Left ovary capsule was focally ruptured. Peritoneal washings showed metastatic carcinoma. Provisional FIGO stage was IC. During sampling, concurrent finding of STIC was documented in right fallopian tube. No invasive carcinoma was present in both entirely submitted fallopian tubes. Key Words: High grade serous carcinoma, Ovary, Serous tubal intraepithelial carcinoma, TP53.

Summary Although several studies have addressed different aspects of mucinous neoplasms arising in the ovary, such as their clinicopathologic features, immunohistochemical profile, and molecular characteristics, no study has presented an analysis of the ovarian tissue where these neoplasms arise. In this study, we included 196 cases of intestinal-type ovarian mucinous neoplasms in premenopausal patients. Our main goal was to perform a rigorous examination of the ovarian tissue surrounding these neoplasms. We also reviewed the clinicopathologic features of these cases. For comparison, the background ovarian tissue in 85 cases of ovarian serous neoplasm and in 29 cases of metastatic neoplasms to the ovary, as well as 57 normal ovaries, was examined. All the patients in this study, which included those with mucinous and with serous neoplasms primary in the ovary, those with metastatic tumors to the ovaries, and those with normal ovaries, were also premenopausal. Patients affected by ovarian mucinous neoplasms ranged in age from 13 to 52 years (median = 36 years). Nulligravidity was seen in 50%, 32%, and 22% of patients with mucinous carcinomas, mucinous borderline neoplasms, and mucinous cystadenomas, respectively. Ovarian mucinous intestinal neoplasms arise in abnormal ovaries characterized by two important features: (1) an abnormal ovarian cortex, seen in 95% of the cases, which is hypocellular or with no distinction between the cellular cortex and medulla, and (2) a remarkable paucity of primordial follicles. The abnormalities detected in the background ovarian tissue might provide insights into the tumorigenesis of these neoplasms and might facilitate their distinction from metastasis to the ovary, in premenopausal patients.

Objective: The purpose of this study was to evaluate the diagnostic utility of SATB2 in detecting CRC origin for patients presenting with metastatic carcinomas. Study Design: Cross sectional, comparative study. Place and Duration of Study: Study was conducted at department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi from January 2019 to June 2019. Materials and Methods: Already diagnosed 68 cases of metastatic carcinoma of various origins with unknown primary were retrieved from tumour registry. Paraffin embedded blocks were taken and a panel of Immunohistochemistry was applied which includes CK7, CK20,CDX2 and SATB2. Positivity of SATB2 alone, and combination of SATB2 with CK 7,CK20 and CDX2 was evaluated. Results: Out of 68 metastatic adenocarcinoma cases 28(41%) had positive SATB2 expression and 38 (56%) were negative. All the positive SATB2 cases had 100 % (28/28) expression with CDX2, 93% (26/28) of the cases had expression with CK20 and 21% (6/28) of the cases showed expression of CK7. The sensitivity of SATB2 alone was 100% in metastatic colorectal carcinoma as compared to CK20 and CDX2. The sensitivity of SATB2 in combination with CDX2 (100%) and CK20 (93%)in comparison to the double combination of CK20 and CDX2(93 %). The sensitivity of SATB2 and CK20 combination was 93%, which was equal to CK20 and CDX2 combination. Conclusions: Our results show that SATB2 is a sensitive marker in the IHC panel for cases with suspected metastasis from colorectal region.

Supplemental Digital Content is available in the text., Background. Metastatic carcinoma of a renal allograft is a rare but life threatening event with a difficult clinical management. Recent reports suggested a potential role of BK polyomavirus (BKPyV) in the development of urologic tract malignancies in kidney transplant recipients. Methods. We investigated a kidney-pancreas female recipient with an history of BKPyV nephritis who developed a rapidly progressive and widely metastatic donor-derived renal carcinoma 9 years after transplantation. Results. Histology and fluorescence in situ hybridization analysis revealed a donor-derived (XY tumor cells) collecting (Bellini) duct carcinoma. The presence of BKPyV oncogenic large tumor antigen was identified in large amount within the kidney tumor and the bowel metastases. Whole genome sequencing of the tumor confirmed multiple genome BKPyV integrations. The transplanted kidney was removed, immunosuppression was withdrawn, and recombinant interleukin-2 (IL-2) was administered for 3 months, inducing a complete tumor clearance, with no evidence of disease at 6-year follow-up. The immunological profiling during IL-2 therapy revealed the presence of donor-specific T cells and expanded cytokine-producing bright natural killer cells but no donor-specific antibodies. Finally, we found persistently elevated anti-BK virus IgG titers and a specific anti-BKPyV T cell response. Conclusions. This investigation showed evidence for the potential oncogenic role of BKPyV in collecting duct carcinoma in renal allografts and demonstrated that immunosuppression withdrawal and IL-2 therapy can lead to an efficient antitumor cellular mediated rejection possibly via 3 distinct mechanisms including (1) host-versus-graft, (2) host-versus-tumor, and (3) anti-BKPyV responses.

Purpose To describe the clinical and pathologic features of a case of epibulbar proliferative fasciitis and to compare it with other focal or diffuse myxoid lesions. Methods A clinical, histopathologic, and immunohistochemical analysis was performed. The clinical history, photographic documentation, history, and referred slides were reanalyzed. Additional immunohistochemical stains were performed at our institution. Results A 68-year-old woman developed over a week a brightly vascularized and focally hemorrhagic placoid lesion on the temporal side of the OS. She had had earlier augmentation breast surgery that had been mistakenly initially reported to us to be for breast carcinoma. Hematoxylin- and eosin-stained reactions revealed microscopically a spindle cell lesion with an intact nonkeratinizing epithelium and a background myxoid stroma with prominent capillaries and a light dispersion of small T-cell lymphocytes. Most striking among the spindle cells were some widely separated large atypical cells. The atypical cells were cytokeratin positive, but an expansive panel of immunohistochemical stains for breast carcinoma was negative. The lesion was diagnosed as proliferative fasciitis and has not recurred after 1-year follow up. Conclusion A rapidly evolving conjunctival lesion is unlikely to be a primary or metastatic carcinoma. In the current case, the large ganglioform or rhabdomyoblast-like cells displayed diffuse cytokeratin positivity, still consistent with a mesenchymal or connective tissue cell lineage. Cytokeratin expression has been a finding previously reported in connective tissue tumors and in lymphoma cells. While the current lesion clinically resembles a conventional nodular fasciitis, the presence of the large atypical cells can lead to the misdiagnosis of a sarcoma, which typically displays a much higher Ki-67 proliferation index in comparison with nodular/proliferative fasciitis.

Background Lymph node fine-needle aspiration (LN FNA) cytology indicates necrosis in various diseases. Dominant necrotic features make the diagnosis of underlying conditions very difficult. Methods We retrospectively reviewed 460 patients who underwent cervical LN aspiration cytology that revealed necrotic findings at Keimyung University Dongsan Hospital in Daegu, Korea, from 2003-2017. Each specimen was evaluated and analyzed in association with the clinical findings, biopsy findings, and/or other ancillary tests, including acid-fast bacilli staining and molecular testing for Mycobacterium tuberculosis. Results When necrotic features were noted upon cervical LN FNA cytology, the most common pathologic LN FNA category was necrosis alone (31.5%). The second most common category was granulomatous inflammation (31.3%), followed by Kikuchi disease (20.0%) and malignant neoplasm (8.7%). In cases where the cervical LN FNA revealed necrosis alone, the most common final diagnosis was tuberculosis. In young patients, Kikuchi disease should be considered as one cervical LN FNA category, while metastatic carcinoma should be suspected in older patients. Conclusions Even when necrosis alone is observed in LN FNA cytology, it is important to determine the cause through further evaluation.

Context.— Renal malignancies can be divided into cortical- and medullary-based tumors, the latter of which classically infiltrate the renal parenchyma by extending between nonneoplastic structures. Although high-grade cortical tumors can rarely exhibit the same growth pattern, the infiltrative morphology should elicit a differential diagnosis to be considered in each case. However, these diagnoses can be challenging to distinguish, especially on small renal biopsy samples. Objective.— To provide an overview of the clinical, gross, and microscopic findings; genetic and molecular alterations; and immunohistochemical evaluation of medullary-based renal tumors and other tumor types with overlapping morphologies and growth patterns. Data Sources.— Literature review and personal observations were used to compile the information in this review. Conclusions.— Collecting duct carcinoma is a prototypical medullary-based tumor, and although diagnostic criteria exist, it remains a diagnosis of exclusion, especially with ancillary techniques aiding the recognition of established as well as more recently described neoplasms. Other medullary-based malignancies included in the differential diagnosis include renal medullary carcinoma/renal cell carcinoma unclassified with medullary phenotype, fumarate hydratase–deficient renal cell carcinoma, and upper tract urothelial carcinoma. Moreover, other rare entities should be excluded, including metastatic carcinoma, lymphoma, and melanoma. In addition to potential prognostic differences, accurate diagnoses can have important surgical and clinical management implications.

A 68-year-old man with a 2-month history of progressive weakness and spontaneous pain in proximal limb muscles presented to our hospital with a dropped head. He started experiencing progressive dysphagia several days before admission. On admission, he had muscle weakness of the limbs and neck extensors with edema and induration in distal extremities. Laboratory tests showed elevation of muscle enzymes. FDG-PET/CT demonstrated multiple hypermetabolic lymph nodes, but the primary site was not identified; thus, metastatic carcinoma of unknown primary origin was considered. The patient was diagnosed with anti-nuclear matrix protein 2 antibody-positive paraneoplastic myopathy based on serum tests. Histological findings of the left biceps brachii muscle biopsy revealed severe variation in fiber size and perifascicular myofiber atrophy. Myofibers exhibited myxovirus resistance protein A expression predominantly in the perifascicular region. Following intravenous methylprednisolone pulse therapy and intravenous immunoglobulin, the patient's muscle strength improved with normalization of muscle enzyme levels. The dropped head was considered to have resulted from the preferential involvement of neck extensors based on the observed FDG-PET/CT uptake in neck extensors.

Fine Needle Aspiration Cytology (FNAC) is a quick, reliable, minimally invasive and cost effective diagnostic modality for evaluation of superficial lymph nodes and has been accepted as a first line investigation in most centres. The aim of the study was to identify the patterns of pathologies in aspiration cytology of lymph nodes in a tertiary care hospital located in Uttar Pradesh, India. The study was undertaken as a retrospective study using data in the Department of Pathology, G.S Medical College and Hospital, Uttar Pradesh, India. 235 lymph node FNACs that were performed during the two year span of 2018-19 were analysed. Females comprised 59.6% of the total patients who underwent lymph node FNAC procedure, 95 (40.4%) were males. The youngest patient was a 3 month old and the oldest happened to be 78 years. Lymph node enlargement was traced to malignant processes exclusively above 40 years of age. Uptill that age, tuberculosis seems to be the major cause underlying lymphadenopathy, mostly presenting as granulomatous lymphadenitis. Out of all cases which showed granulomatous or necrotic features, 27% showed the presence of AFB, hence confirming tuberculosis. A vast majority of the FNACs were performed for cervical lymphadenopathy (92.8%). 42.1% of the FNACs revealed reactive morphology. This diagnosis was closely followed by granulomatous lymphadenitis in 29.4% patients. Together with a definite diagnosis of tuberculous lymphadenitis, patients with granulomatous lymphadenitis comprised 42.6% of all diagnoses. 12 patients received a diagnosis of suppurative lymphadenitis, 9 received necrotizing lymphadenitis. 12 patients were diagnosed as metastatic carcinoma and 1 was suggestive of lymphoma. Most of the lymph nodes whose sizes were under 1 cm were reactive on cytology. Lymphadenopathy due to malignant etiology presented with lymph nodes measuring at least 2 cm. Granulomatous/tuberculous lymphadenitis presented in lymph nodes of varying sizes, from as small as 0.5 cm to larger ones.

Metastatic small bowel tumors in the testes are uncommon often indicating an advanced stage of sickness with poor prognosis. The route of spread to the scrotal level has not yet been defined. The most of these tumors are diagnosed at autopsy or orchiectomy for metastatic carcinoma. The diagnosis is mainly based on histological and immunohistochemical data. In this paper, we report the case of a 36-year-old patient with a spermatic torsion secondary to a testis metastasis from an adenocarcinoma of the small intestine confirmed histologically, occurring as first clinical manifestation that was taken care in the medical oncology department of CHU Hassan II in Fes. The aim of the subject is to highlight this rare metastatic localization of gastrointestinal cancer; how to approach the diagnosis and distinguish between primary testicular cancer and testicular metastasis; by describing the different clinical, radiological and anatomopathological aspects of metastatic gastrointestinal cancer to the testis.

Introduction: Secondary cardiac malignancies are much more common than primary cancers. Metastatic cancers to the heart from other solid organs are well known and carry a poor prognosis. Case Presentation: An 83-year-old Hispanic veteran presented with breathlessness, cough, and weight loss. Imaging studies showed extensive pericardial effusion and multiple pericardial/epicardial masses. Biopsy showed poorly differentiated metastatic carcinoma with no definitive origin, based on lab, imaging, and extensive immunohistochemistry (IHC) studies. Gene panel testing showed microsatellite stable status. Programmed cell death 1 ligand (PD-L1) IHC was 100% in the tumor cells. He was started on pembrolizumab and had a complete resolution of symptoms. Subsequent imaging studies showed improvement in the multiple pericardial/epicardial masses. Discussion: Immune checkpoint inhibitor (ICI) therapy has changed the treatment landscape of many malignancies since the approval of the first ICI, ipilimumab, for melanoma in 2011. To the best of our knowledge, this is the first reported case of successful treatment by ICI therapy in undifferentiated metastatic carcinoma of an unknown primary source to the heart.

Background: The diagnosis of atypical cases in the effusion cytology sample often poses a challenge to the cytologists. Aims and Objectives: We evaluated the diagnostic role of MOC31 in the metastatic adenocarcinoma in effusion fluid. Materials and Methods: The cytological examination and MOC31 immunostaining in the cell block sections were carried out in 64 cases of serous effusion. A total of 23 cases showed atypical cytology, out of which suspicious for malignancy (SFM) and atypia of undetermined significance (AUS) were 19 and 4 cases, respectively. In these cases, we also performed calretinin immunostaining. The cytological features, results of MOC31 immunostaining, and follow-up data were correlated to find out the sensitivity and specificity of MOC31 immunostaining in the diagnosis of metastatic adenocarcinoma. Result: The sensitivity and specificity of MOC31 were 100%. MOC31 detected all the cases of metastatic adenocarcinoma. MOC31 showed strong positivity in 19 cases of SFM. All these cases had a malignant outcome in histopathology or follow-up data. In AUS cases, MOC31 immunostaining was negative with a benign outcome. In all the atypical but malignant cases calretinin stain showed diffuse cytoplasmic and nuclear positivity. In contrast, MOC31 showed strong membranous positivity and occasionally cytoplasmic positivity. Conclusion: MOC31 is an excellent marker of metastatic adenocarcinoma in the serous effusion. The membranous positivity of MOC31 and negative calretinin immuno­staining are helpful in atypical cytological cases to avoid the diagnostic dilemma. The MOC31 positivity is significantly useful in discrete atypical cells which are more challenging to recognize.

Introduction: The head and neck area is a complex anatomical structure which includes various nonneoplastic and neoplastic lesions of lymph node, salivary gland, thyroid gland and soft tissue. Fine needle aspiration cytology of head and neck lymph nodes proved useful in separating inflammatory lesions, which do not require surgical excision from cystic and neoplastic lesions with good certainty. Fine needle aspiration cytology (FNAC) is a simple, feasible, cost effective and minimally invasive procedure. But histopathological examination is more valuable for confirmatory diagnosis in suspected lesions. Aim: To assess the utility of FNAC in diagnosis of head and neck lymph node lesions and to establish the diagnostic accuracy of cytology by comparing with the histopathological diagnosis, wherever possible. Materials and Methods: A 6 months retrospective study was done from March 2020 to August 2020 at Khaja Bandanawaz institute of medical sciences on 50 patients presenting with head and neck lymph node enlargement. Result: 50 cases were evaluated by FNAC. In this study out of 34 benign cases, 14 cases were of Reactive lymphadenitis, 17 cases of Granulomatous/Tuberculous lymphadenitis and 3 cases were of Acute suppurative lymphadenitis. Out of 16 malignant cases, 5 cases were of Non Hodgkins lymphoma, 2 cases were of hodgkins lymphoma and 9 cases were of metastatic carcinoma. Conclusion: FNAC has been found to be a satisfactory tool in the diagnosis of tubercular and malignant lymphadenopathy in our study. The lucidity and rapidity of the procedure makes it most appropriate for use on outpatient basis even in peripheral hospitals and dispensaries. Keywords: FNAC, Head and neck, Lymphadenopathy, Tuberculous lymphadenitis.

Early gastric cancer (EGC) with synchronous distant metastasis is extremely rare. Here, we report a case of stage IV Epstein-Barr virus (EBV) -associated EGC. A 51-year-old man presented with vague abdominal pain of 3 weeks' duration. Imaging studies revealed enlargement of the left supraclavicular, perigastric, and para-aortic lymph nodes, a huge gastric polypoid mass, and multiple liver masses. Histopathological examination of a biopsy specimen of the supraclavicular lymph node showed poorly differentiated carcinoma expressing EBV in tumor cell nuclei. The gastric mass exhibited tubular adenocarcinoma, which also expressed EBV in tumor cell nuclei. After 3 weeks of palliative chemotherapy with fluoropyrimidine and platinum, the patient died of liver failure. Next-generation sequencing analysis revealed mutation of the CDKN1B gene in the metastatic carcinoma and mutations of the CTNNB1 and PIK3R1 genes in the gastric carcinoma. In addition to the rare presentation of EBV-associated EGC, this case showed marked morphological and molecular differences between primary and metastatic tumors, which suggests clonal evolution of EBV-associated GC.

Introduction: Fine needle aspiration cytology (FNAC) forms one of the first diagnostic tools in evaluation of soft tissue lesions. Aim of this study was to evaluate the role of FNAC in the primary diagnosis of soft tissue tumors and tumor like lesions and to assess the effectiveness of FNAC in the histological subtyping and grading of soft tissue tumors. Materials and Methods: We reviewed FNAC smears of 170 soft tissue tumors and tumor like lesions over a 3 years period and correlated with the histopathological features which were available in 117 cases. Conventional Papanicolaou (PAP) and Giemsa staining was done in all cases. Results: 152 out of 170 cases [89.41%] were neoplastic, of which 130 tumors were labelled as benign. Lipoma constituted 83.07% of benign tumors. Based on the predominant cytomorphological features and background, the tumors were classified into myxoid (4), spindle cell (20), pleomorphic (2), small round cell(4), epithelioid /polygonal cell (7), lipomatous (108) and miscellaneous (7). The non-neoplastic lesions included tuberculosis, filariasis, actinomycosis, scar endometriosis and calcinosis cutis. Conclusion: FNAC proved to be helpful in distinguishing between neoplastic and non-neoplastic soft tissue lesions, differentiating metastatic carcinoma and melanoma in soft tissue from primary soft tissue tumors and differentiating benign and malignant soft tissue tumors. Accurate subtyping was possible in many tumors of myxoid category and round cell tumors. Spindle cell tumors of intermediate grade were difficult to grade on FNAC. Pleomorphic sarcomas were of high grade and their subtyping could not be done on FNAC. Keywords: FNAC, Soft tissue lesions, Soft tissue tumors.

A 62-year-old woman was referred for evaluation of a nonhealing epithelial defect of the left eye. Examination also revealed left upper lid ptosis, cicatricial lagophthalmos, and palpable lid masses. With probing, the patient admitted to recent history of lobular carcinoma and remote history of ductal carcinoma of the breast. Imaging showed abnormal tissue in the left extraconal orbit involving the lacrimal gland. After orbitotomy and biopsy of the mass, pathology specimens returned consistent with metastatic carcinoma of the left orbit with breast as the site of the primary tumor. The patient completed palliative radiation therapy and chemotherapy. Amniotic membranes were placed to promote healing of the persistent epithelial defect with good response. Unfortunately, the patient died approximately 1 year after her initial presentation secondary to her oligometastatic disease. There is a wide spectrum of clinical manifestations associated with orbital metastasis. Careful consideration must be given to cancer patients with ophthalmologic complaints.

The third part of literature review (see first part in ROJ 2019; 12 (4): 99–108, second part in ROJ 2020; 13 (2): 88–98) discusses the features characteristic of small uveal melanoma and pseudomelanomas (choroidal nevus, circumscribed choroidal hemangioma, melanocytoma, choroidal metastatic carcinoma, congenital hypertrophy of retinal pigment epithelium, late-stage age-related macular degeneration, focal retinochoroiditis, organized subretinal hemorrhage, retinal hemangioma) which were revealed by optical coherence tomography and optical coherence tomography-angiography. The need for further comparative studies aimed at defining differential diagnostic is emphasized.

Cancers of the oral cavity are one of the most common malignancies encountered among cancer patients in India.1 There are different histological variants of oral cavity cancers, and squamous cell carcinoma (SCC) is most common among them. The main etiological factors implicated for development of oral cavity cancers are tobacco chewing and alcohol use.2 In India, carcinoma of buccal mucosa has the highest incidence among all the oral cavity cancers.3 The mean age of presentation is 50 years.4 Incidence among males is three times that of females.5 Most of the patients present in advanced stage (Stage III & IV) with majority in stage IV.6 Metastasis from oral cavity cancer takes place by detachment, invasion, proliferation and evasion through lymphatic system and blood vessels. It is regulated at various levels in the body.7 Most common sites of distant metastasis from oral cavity cancers are lungs and liver. Sometimes vertebral bone metastasis is also seen among patients. Metastasis to omentum and intra peritoneal organs other than liver is very rare.

Sentinel lymph node biopsy is gaining increasing acceptance as a less morbid way to assess lymph node status in patients with endometrial carcinoma, compared with full pelvic node dissection. The sentinel nodes are usually subjected to ultrastaging, with sections taken at multiple levels from each block and immunstaining for keratin performed, in order to detect micrometastses. We report a case of an 80-yr-old woman who underwent a right sentinel lymph node biopsy at the time of surgery for clinically and radiologically apparent stage I endometrial endometrioid adenocarcinoma. The immunostains for AE1/AE3 performed on the 2 right pelvic sentinel lymph nodes were positive, corresponding to subcapsular acellular keratin on hematoxylin and eosin; however, carcinoma cells could not be identified on the hematoxylin and eosin-stained slides. Immunomarkers for Ber-EP4 and EMA, both of which were strongly expressed in the endometrial carcinoma cells, were negative on the nodal tissue, and we concluded that the sentinel lymph nodes were negative for metastatic carcinoma, despite the positive keratin immunostains. To our knowledge, this unusual finding is not described in the literature; recognition of this phenomenon and study of additional cases is warranted.

Introduction We evaluated the role of simultaneous use of multiple antibodies in flow cytometry (FCM) to detect metastatic carcinomas in effusion samples. Methods Cytological examination of 75 successive cases of effusion samples was performed. There were 48 peritoneal, 26 pleural and one pericardial fluid. Multi-coloured FCM examination was undertaken using a cocktail of CD45, CD14 and epithelial cell adhesion molecule (EpCAM), antibodies tagged with different fluorochromes. The percentage of EpCAM positivity was calculated in the CD45 and CD14 dual negative population by selective gating. The EpCAM value was correlated with the cytological findings, follow-up data and MOC-31 immunostaining. Results There were 20 benign, 35 malignant and 20 atypical cases diagnosed on cytomorphology. The primary sources of carcinomas were mainly from the ovary, followed by lung, gall bladder, intestine and other areas. Out of 20 cytologically benign cases, there were two malignant cases on the final follow-up, and EpCAM on FCM picked up all 18 benign cases and one malignant case. Out of 35 cytologically detected malignant cases, EpCAM picked up 32 malignant cases. The EpCAM detected 15/18 malignant and both benign cases out of 20 cytological atypical cases. EpCAM antibody by FCM showed 87% sensitivity, 100% specificity, 100% positive predictive value and 74% negative predictive value. Conclusion This comprehensive study highlights the potential use of multi-coloured FCM along with cytological examination to diagnose metastatic carcinoma in effusion samples. Multi-coloured FCM is rapid and quantitative and is helpful in atypical cases.

Tumour-to-tumour metastasis is very unusual and has been defined as a tumour metastasis into another histologically different tumour. It is extremely rare in bone. We report a case of lung squamous cell carcinoma metastasized to an enchondroma in the femur of a patient with Ollier disease. A 60-year-old female had a history of a poorly differentiated squamous cell carcinoma of the lung. She underwent a video-assisted thoracoscopic lobectomy, and a follow-up MRI scan showed three lesions in the left distal femur and proximal tibia, which were initially interpreted as metastasis on radiology. Resection of the left proximal tibial lesion was performed, and the pathological findings were consistent with enchondroma with no evidence of metastasis. Subsequent curettage of lesions in the distal left femur revealed metastatic poorly differentiated carcinoma with foci of hyaline cartilage, which was most consistent with metastatic carcinoma in a pre-existing enchondroma. The MRI films were re-reviewed. Characteristic MRI features of enchondroma were found in the lesion in the left proximal tibia and one of the lesions in the left distal femur, while the features of the other lesion in the left distal femur included cortical destruction and extensive oedema in surrounding soft tissue, which were consistent with a malignant tumour. In addition, the enchondroma in the lateral condyle showed blurring and irregular inner margin and adjacent bone oedema, which likely represents a co-existing metastatic tumour and enchondroma. The difference in lineage was confirmed by immunohistochemistry. The final diagnosis was metastatic poorly differentiated carcinoma of the lung into a co-existent enchondroma. The diagnosis can be challenging and could be easily overlooked both radiologically and histologically. Thorough clinical and radiological information is critical for the diagnosis, and despite a very unusual event, awareness of the tumour-to-tumour metastasis phenomenon can avoid an inaccurate diagnosis by the pathologist, therefore preventing inappropriate clinical intervention.

Introduction: Lymph nodes are a site for organized collections of lymphoreticular tissue and arepink-gray bean-shaped encapsulated organs. Lymph nodes are among the commonly aspiratedorgans for diagnostic purposes. Lymphadenopathy is of great clinical significance as underlyingdiseases may range from a treatable infectious etiology to malignant neoplasms Fine needleaspiration cytology (FNAC) is a reliable as well as an inexpensive method used to diagnoselymphadenopathy of various sites. Aims: To evaluate the usefulness of FNAC as a diagnostic tool inthe etiological causes of lymphadenopathy and to study the cytomorphological features associatedwith various lymphadenopathies. Materials and Methods: The present prospective study wascarried out in the Department of Pathology at Maharajah's Institute of Medical Sciences,Vizianagaram, a Tertiary Care Centre. A total of 210 patients of all age groups underwent FNAC ofenlarged lymph nodes during this study period. Results: FNAC diagnosis was found to be as follows:tubercular lymphadenitis in 98 cases (46.67%) followed by reactive hyperplasia in 35 cases(16.67%), metastatic carcinoma 29 (13.8%), granulomatous lymphadenitis 27 (12.85%), non-specific lymphadenitis 8 (3.8%), acute suppurative lymphadenitis 7 (3.33%) and lymphoma 4 (1.8).Conclusion: FNAC of lymph nodes is an excellent first-line investigation to determine the nature ofthe lesion. It is quick, safe, minimally invasive, and reliable and is readily accepted by the patient.

Androgen Receptor (AR) signaling is a critical driver of hormone-dependent prostate cancer and has also been proposed to have biological activity in female hormone-dependent cancers, including type I endometrial carcinoma (EMC). In this study, we evaluated the preclinical efficacy of a third-generation AR antagonist, enzalutamide, in a genetic mouse model of EMC, Sprr2f-Cre;Ptenfl/fl. In this model, ablation of Pten in the uterine epithelium leads to localized and distant malignant disease as observed in human EMC. We hypothesized that administering enzalutamide through the diet would temporarily decrease the incidence of invasive and metastatic carcinoma, while prolonged administration would result in development of resistance and loss of efficacy. Short-term treatment with enzalutamide reduced overall tumor burden through increased apoptosis but failed to prevent progression of invasive and metastatic disease. These results suggest that AR signaling may have biphasic, oncogenic and tumor suppressive roles in EMC that are dependent on disease stage. Enzalutamide treatment increased Progesterone Receptor (PR) expression within both stromal and tumor cell compartments. Prolonged administration of enzalutamide decreased apoptosis, increased tumor burden and resulted in the clonal expansion of tumor cells expressing high levels of p53 protein, suggestive of acquired Trp53 mutations. In conclusion, we show that enzalutamide induces apoptosis in EMC but has limited efficacy overall as a single agent. Induction of PR, a negative regulator of endometrial proliferation, suggests that adding progestin therapy to enzalutamide administration may further decrease tumor burden and result in a prolonged response.

Background Intraductal papillary neoplasm of the bile duct (IPNB) is considered a pre-cancerous biliary lesion and/or an early cancer lesion, although its classification remains unclear. The 2019 revised edition of the World Health Organization Classification of Tumors of the Digestive System proposed type 1 and type 2 as new classification categories, and meta-analyses and/or multi-center cohort studies are beginning to be reported. However, treatment for IPNB recurrence and metastasis remains unclear. Case presentation A 60-year-old man who was referred to our hospital after a suspected liver tumor was diagnosed using abdominal ultrasonography. Imaging findings revealed an irregularly shaped tumor in segment 5 (S5) of the liver (size 20 mm). The S5 lesion was suspected as IPNB, and segmentectomy was performed. The pathological findings revealed invasive carcinoma derived from IPNB, and immunohistochemistry revealed positive expression of MUC1, MUC5AC, and MUC6, but negative expression of CDX2 and MUC2. At 9 months after the surgery, computed tomography revealed a tumor in the right bile duct, which was diagnosed as liver recurrence of IPNB, and right hepatectomy was performed. The histopathological findings were the same as for the first resected specimen (i.e., IPNB). At 45 months after the second surgery, computed tomography revealed nodules in both lungs, which were diagnosed as lung metastases from IPNB and resected in two separate procedures. The pathological findings were metastatic carcinoma from IPNB for both lung lesions. The patient is currently alive and undergoing adjuvant chemotherapy (S-1), which was initiated 64 months after the first resection and 12 months after resection of the lung metastases. Conclusion We encountered a rare case of lung metastases from IPNB, which were diagnosed immunohistologically. Because IPNB is generally a slow-growing tumor, resection may be feasible for IPNB recurrence and/or metastasis, which may be detected during long-term follow-up. Thus, even if resection is performed for primary IPNB, additional surgical treatment may be feasible in this setting.

A 73-year-old man presented with a three-week history of weakness and loss of co-ordination of the left-hand side and weakness of left-hand grip. MRI brain revealed an enhancing lesion in the right parietal lobe, adjacent to the central sulcus, with surrounding oedema and a small satellite lesion in motor cortex. Body CT and FDGPET CT revealed no obvious primary neoplasm. The patient underwent craniotomy with resection of the lesion, subsequent histopathology confirmed a metastatic carcinoma of likely prostate cancer primary origin. The patient was on 5-ARI (Finasteride) for lower urinary tract symptoms that decrease serum PSA levels to half and had benign feeling prostate on digital rectal examination (DRE). Subsequent MRI prostate confirmed presence of a lesion with very high probability of prostate cancer. The patient’s serum Prostate Specific Antigen (PSA) level was 6.8 (13.6 corrected for Finastride) which is relatively low in the context of metastatic disease. Given the recent NICE guidelines of using pre-biopsy multiparametric MRI (mpMRI) for diagnosis of prostate cancer, we suggest that in patients with cerebral metastases of unknown primary, with negative body CT, FDG PET-CT, low PSA and negative DRE, mpMRI prostate should be included in diagnostic protocol in the selected group of men, to enable early diagnosis and performing more suitable and targeted treatment. Keywords: Brain metastasis; prostate cancer; multiparametric MRI; metastasis of unknown origin

Background Secondary carcinoma involving the gastrointestinal (GI) tract is an uncommon finding in biopsy specimens. The diagnosis can be challenging for tumours mimicking a primary carcinoma and when the clinical context is unknown. Methods and results A multicentre retrospective study was performed to evaluate the clinical and histological features of a series of secondary carcinoma in GI biopsies. A total of 197 cases from 190 patients (median age = 67 years; 57% females) were reviewed. In 16% of patients, the primary carcinoma was unknown. Most lesions presented endoscopically as mucosal or submucosal masses (58%). In 13%, the endoscopy was non-suspicious for malignancy. The most common tumours were carcinomas of the breast (38%), kidney (13%), lung (12%), prostate (8%) and ovary (7%). The sites of involvement were the stomach (34%), colon (27%), rectum (18%), duodenum (13%), oesophagus (5%), jejunum (3%) and anus (0.5%). Histological patterns of infiltration were mucosal (76%), submucosal (41%), lymphatic (14%), and epithelial colonisation (8%). Submucosal infiltration was found significantly more frequently in carcinomas of the prostate (67%) and lung (62%), compared with carcinomas of the ovary (27%) and breast (23%). Histological obstructive changes were observed in 36% of all cases, with the highest rate in prostate carcinoma (53%) and the lowest rate in kidney carcinoma (8%). Conclusion Awareness of the main clinical and histological patterns of secondary carcinomas in GI tract biopsies may help pathologists to raise the possibility of this uncommon diagnosis and confirm it with the judicious use of immunohistochemistry.

This study aimed to evaluate the clinical effects of percutaneous vertebroplasty (PVP) combined with postoperative radiotherapy (RT) in the treatment of spinal metastases. Nine patients (4 males and 5 females, mean age 59.56 years) with painful pathologic compression vertebral fractures caused by metastatic cancers of the spine (5 thoracic levels, 8 lumbar levels) were admitted to our hospital between July 17, 2016 and September 25, 2018. All patients were treated with PVP via bilateral pedicle approach combined with postoperative RT to treat metastatic lesions of the centrum. The clinical records of the patients were retrospectively analyzed. Patients’ demographic features and medical conditions including the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and Imageology data were observed. Patients’ mean VAS scores decreased from 8.67 ± 0.50 preoperatively to 1.78 ± 0.83 at 6 months after PVP. Moreover, the mean ODI score decreased from 74.07 ± 13.15 preoperatively to 31.87 ± 10.00 at 6 months after PVP. Significant improvement in the degree of pain and dysfunction among the enrolled patients were observed. Furthermore, the metastatic carcinoma lesion within the vertebral body was well controlled according to imaging. PVP in conjunction with postoperative RT is a good treatment strategy for vertebral compression fractures caused by metastases.

Carcinoma of unknown primary (CUP) syndrome occurs when metastases from an unknown primary site spread to multiple organs. Occult breast cancer (OBC) is defined as a clinically recognizable metastatic carcinoma from an undetectable primary breast tumor. It accounts for 0.3–1% of all breast cancers, often presenting with lymph node, bone, and skin metastases. Clinical and radiological examinations represent the first steps in the diagnostic algorithm for CUP syndrome from OBC. However, histological and immunohistochemical analyses, multidisciplinary team evaluation, and a multidisciplinary therapy are essential in the diagnosis and treatment of CUP syndrome from OBC. We report the case of a 52-year-old woman who underwent the removal of a parietal skin lesion. The histological and immunohistochemical analyses suggested a breast cancer origin. Clinical assessment and laboratory and radiological examinations did not locate the primary tumor. Hormone therapy was offered to the patient; however, she refused it. After 28 months, the patient reported a right cervical lump, and a total-body positron emission tomography showed dissemination of the disease to the lymph nodes and bone. A CUP syndrome from OBC was diagnosed. A multimodality approach with radiotherapy and hormone and biological therapy was started. At present, 5 years from the first presentation, the patient is asymptomatic despite the disseminated disease.

Background Hepatic epithelioid hemangioendothelioma is an extremely rare malignant vascular tumor which is often multifocal and, in many cases, discovered incidentally. Here, we describe the clinicopathological features of hepatic epithelioid hemangioendothelioma cases seen in our practice and present a detailed review of the published literature. Methods All cases of hepatic epithelioid hemangioendothelioma diagnosed in Department of Pathology and Laboratory Medicine, Aga Khan University Hospital between January 1, 2006 and December 31, 2019 were included in the study. Slides were reviewed and follow up was obtained. Results Seven cases were reported during the study period. There were 4 females and 3 males. Age range was 20 to 77 years, mean age was 45 years. Three patients presented with right upper abdominal pain; 1 patient presented with jaundice while 3 patients were asymptomatic. In all 7 cases, lesions were identified on imaging studies. In 5 cases, liver lesions were multifocal. Clinical differential diagnosis in all cases was metastatic carcinoma and multifocal hepatocellular carcinoma. Liver function tests were normal in 5 cases. In 1 patient, tumor had already metastasized to the right lung. On histological examination of liver core biopsies performed in all 7 cases, classic histological features of epithelioid hemangioendothelioma were seen. Tumor cells expressed positivity for vascular markers (CD 34, CD31 and ERG) and were negative for cytokeratins, Hep par 1 and Glypican 3. Surgical resection was not performed in any of the 7 cases and all patients were treated by chemotherapy. Follow up was available in 5 cases. Of these, 3 patients died of disease and another patient was alive with metastases in both lungs, omentum and colon. Conclusion Clinicopathological features of the 7 cases in our series and detailed review of published literature is presented. Prognosis was bad in our cases most likely due to fact that surgical resection could not be performed in any of the cases owing to lack of surgical expertise for liver tumor surgery in most parts of the country.