Establishing the First Diagnosis of Hepatocellular Carcinoma in Lung Biopsy in a 47-Year-Old Man: A Case Report

Hepatocellular carcinoma (HCC) is a primary tumor of the liver.  The most common metastatic sites include lung, lymph node, and bone. The diagnosis of HCC is usually through radiological examination and liver biopsy. The first diagnosis of HCC through a metastatic site is very rare. Here, we report a case that the first diagnosis of HCC was not through liver biopsy, but rather by a lung biopsy. The patient was a 47-year-old man with elevated AFP level. Abdominal CT and MRI showed liver nodules and lung nodules. A liver biopsy was performed, showing cirrhotic liver with extensive fibrosis. No malignancy can be identified. A lung biopsy was performed. Microscopic examination showed abundant polygonal cells with eosinophilic cytoplasm forming trabecular pattern with endothelial wrapping. These cells are positive for HepPar-1, and focally positive for Glypican-3, and negative for CK7, CK20, TTF-1, Napsin A, synaptophysin and chromogranin, consistent with metastatic hepatocellular carcinoma. The negative staining results of PAX-8, CD10, and EMA do not support differential diagnosis of metastatic renal cell carcinoma. This case raises the awareness that the first diagnosis of HCC can be through a metastatic site, especially when well-differentiated HCC is difficult to distinguish from benign hepatic masses, such as macroregenerative nodules, adenoma, or focal nodular hyperplasia. [N A J Med Sci. 2025;18(1):005-008.   DOI: 10.7156/najms.2025.1801005]   Key Words: Hepatocellular carcinoma (HCC), well-differentiated HCC, immunohistochemistry, Glypican-3, HepPar-

A Case Report of BAP1-inactivated Melanocytoma with Discussion of Possible Dual Roles of BAP1 Loss in Tumorigenesis

BRCA1-associated protein (BAP1) is a tumor suppressor involved in a myriad of cellular processes. BAP1-inactivated melanocytomas (BIMs) are rare melanocytic tumors characterized by the loss of nuclear expression of BAP1. Here, we report a case of a 33-year-old female presenting with a cutaneous macule on the left lateral nasal wall. Histopathological examination revealed a dermal-based melanocytic neoplasm comprised of large epithelioid melanocytes with pleomorphic nuclei, some with multinucleation. Due to the morphology atypia, melanoma was suspected. However, PRAME (PReferentially expressed Antigen in MElanoma) immunohistochemical staining was negative, and further BAP1 staining showed loss of nucleus expression. Chromosomal microarray confirmed the loss of chromosome 3 (including BAP1) and chromosome X. Compared with malignant melanoma, most BIMs follow indolent courses. We further discussed the possible molecular pathogenesis of BIMs and propose that although the loss of BAP1 predisposes melanocytes to form tumor, it may hinder the development of more malignant forms. Hence, BAP1 may emerge as an interesting target for exploring synthetic lethality to better understand melanoma pathogenesis. [N A J Med Sci. 2025;18(1):009-012.   DOI: 10.7156/najms.2025.1801009]   Key Words: BRCA1-associated protein (BAP1), BAP1-inactivated melanocytomas (BIMs), tumorigenesi

An Unusual Case of Invasive Carcinoma with Squamous and Low-Grade Glandular Features Arising in a Giant Condyloma Acuminatum

We report an unusual case of invasive carcinoma with both squamous and glandular features arising in a giant anorectal condyloma acuminatum (GCA). The challenging part in rendering a definite diagnosis was the presence of a glandular component, its differentiation from other entities with similar histomorphology and low-grade human papilloma virus (HPV) expression in tumor cells. A 70-year-old woman presented with long standing symptoms of rectovaginal bleeding and recurrent perianal fistulas. She underwent an end-colostomy and later, an abdominoperineal resection. A large anorectal tumor was identified with associated invasive carcinoma showing both squamous and low-grade glandular features. The tumor recurred as pelvic mass within 6 months requiring chemoradiation therapy.  The abdominoperineal resection specimen showed a large (> 5cm) verrucous mass at anorectal junction with an endophytic component invading vaginal fistulas and adjacent soft tissue. Histologically, the exophytic tumor had condylomatous proliferation with koilocytosis. The endophytic part showed invasive carcinoma with both squamous and low-grade glandular features. The glandular component was positive for CK7 and negative for CK20 and CDX-2, suggesting anal gland origin rather than a colorectal primary. High-risk HPV and p16 were both negative. In-situ hybridization (ISH) demonstrated low-grade HPV in tumor cells. GCA, also known as Buschke-Lowenstein tumor, occurs mostly in men and rarely transforms to invasive squamous cell carcinoma. Our female patient presented with recurring perianal fistulas and bleeding without detection of a condylomatous mass until after radical surgery. In addition, GCA associated with this particular pattern of squamous cell carcinoma (one with a glandular component) is exceedingly rare. The differential diagnoses included mucoepidermoid carcinoma, adenosquamous carcinoma and squamous cell carcinoma with mucinous microcystic pattern. The presence of low-risk HPV on ISH test, not only in the condyloma but also in the squamous and glandular cells of the invasive carcinoma, raises a question of its impact in tumor progression from condyloma to squamous as well as glandular invasive carcinoma. Besides being a diagnostic challenge, the clinical implication of this finding remains to be determined. [N A J Med Sci. 2025;18(1):013-017.   DOI:  10.7156/najms.2025.1801013

Case Report: A Composite Diffuse Large B-cell Lymphoma and Classic Mantle Cell Lymphoma in the Small Intestine

Composite lymphomas, defined as the coexistence of two distinct lymphoma subtypes within the same tissue, are rare entities, comprising only 1–4.7% of all lymphomas. Among these, the concurrent occurrence of diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) is exceedingly rare, with only a handful of cases reported. Accurate diagnosis and tailored treatment are critical given the distinct biological and clinical behaviors of these lymphomas. Here, we report the case of a 71-year-old male with a history of Crohn’s disease, presenting with a mass involving the ileocecal valve and terminal ileum, revealed on imaging and confirmed via right hemicolectomy and small bowel resection. Histopathological analysis identified two adjacent but immunohistochemically distinct lymphomas: a classical MCL with nodular architecture and a high-grade DLBCL. Immunohistochemistry and fluorescence in situ hybridization (FISH) studies demonstrated that the MCL expressed SOX11, Cyclin D1, and CD5, with CCND1/IGH translocation present, while the DLBCL lacked these markers, confirming the two lymphomas were clonally unrelated. This case represents the first reported composite lymphoma of MCL and DLBCL arising in the small intestine. The distinction between these two lymphomas was achieved through a combination of morphological, immunohistochemical, and genetic analyses. The rarity and heterogeneity of composite lymphomas pose diagnostic and therapeutic challenges, emphasizing the need for comprehensive evaluation. Given the aggressive nature of DLBCL, treatment often prioritizes this component, although the individualized management of composite lymphomas remains essential. This case highlights the importance of thorough diagnostic workup, including advanced immunohistochemistry and genetic studies, to differentiate between lymphoma subtypes within composite lymphomas. Excisional biopsy remains critical to minimize sampling bias, and further research is needed to understand the pathogenesis and optimize treatment strategies for these rare entities. [N A J Med Sci. 2024;18(1):001-004.   DOI:  10.7156/najms.2024.1801001

Granulomatous Epididymo-Orchitis, A Rare Complication of Bacillus Calmette-Guerin Immunotherapy for Bladder Cancer: A Case Report

Granulomatous epididymo-orchitis (GEO) is a rare disease characterized by granulomatous inflammation due to etiologies such as infection with mycobacteria. A well-known mycobacterial infection, Mycobacterium tuberculosis (M. tb) which causes tuberculosis (TB), can disseminate from the lungs to infect other organs. However, a mycobacterial infection in the genitourinary system without clinical evidence of TB is unusual. A 79-year-old man with nonmuscle invasive papillary urothelial carcinoma (PUC) was treated with chemotherapy and Bacillus Calmette-Guerin (BCG) immunotherapy, a live-attenuated strain of Mycobacterium bovis (M. bovis). One year later, he developed an epididymal cyst on the left testicle and an enlarged left epididymis. A simple left orchiectomy was performed. Microscopic examination showed granulomas within the testicular and epididymal parenchyma. Ziehl-Neelsen (AFB) stain revealed scattered acid-fast bacilli. The positive AFB stain raised the possibility of TB infection. However, the patient had no clinical evidence of latent or active TB, family history of TB, or TB treatment in the past. Here, we present a rare case of GEO, not caused by TB, but by BCG, a live-attenuated strain of M. bovis. [N A J Med Sci. 2024;17(1):008-010.   DOI:  10.7156/najms.2024.1701008]  Key Words: granulomatous epididymo-orchitis, bacillus calmette-guerin (BCG), Mycobacterium bovis, complication of BCG, tuberculosis (TB

Lamotrigine Reduces the Number of Vertigo Attacks in Patients with Meniere’s Disease: A Pilot Study

Spontaneous episodes of vertigo, called vertigo attacks, are the most disabling symptom of Meniere’s disease (MD). The purpose of this study was to compare the number vertigo attacks in patients with MD before and after establishing a maintenance dose of lamotrigine (Lamictal ®). A retrospective chart review was conducted on patients who were diagnosed with definite, unilateral MD, and prescribed lamotrigine for potential management of MD vertigo attacks. Patients were divided into two groups based on whether they had a history of migraine because migraine is one factor that distinguishes MD clinical subgroups. The number of vertigo attacks experienced by each patient was retrieved from clinic visit notes. The number of vertigo attacks in the 12 weeks prior to prescription of lamotrigine (Baseline) and in the first 12 weeks on a maintenance dose of lamotrigine (Maintenance) were compared via paired t-tests within the groups. Overall, thir-ty-three patients met criteria, of which 13 had and 20 did not have history of migraine. The number of attacks reported during Maintenance was significantly less than that reported during Baseline both for patients with (p = 0.001) and without (p = 0.0005) history of migraine. Both MD patients with and without migraine reported fewer vertigo attacks while on a maintenance dose of lamotrigine than prior to prescription of lamotrigine. [N A J Med Sci. 2024;17(1):008-010.   DOI:  10.7156/najms.2024.1701008]  Key Words: Lamictal, episodic dizziness, endolymphatic hydrops, vestibular migraine,migraine-associated vertigo, vestibular disorders, hearing loss, tinnitu

Incidence and Outcomes of Primary Cutaneous Anaplastic Large Cell Lymphoma: a SEER Population Based Study

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is the second most common type of cutaneous lymphoma of T cell origin. Despite its higher prevalence among dermal lymphoma, its overall incidence is rare; hence, its demographic characteristics and outcome is not well explored. Here, we have examined the epidemiologic features and outcomes in PC-ALCL in the population of the United States. First, we identified patients with PC-ALCL from the Surveillance Epidemiology and End Results database from 1975 - 2017. Cases with only histological and immunohistochemical or molecular evidence of diagnosis were included in the study. Age, sex, and race-standardized incidence rates (IR) were calculated. Survival was assessed using Kaplan-Meier curves and Cox proportional hazards models. Of all 569 cases documented as PC-ALCL, 93 patients fulfilled the inclusion criteria. We found the incidence of PC-ALCL to be highly correlated with increased age. There is a predominance of PC-ALCL in white male population. The survival analysis did not signify age of diagnosis, sex, or race as factors affecting the outcome for the patients. Although the site of primary tumor trends towards affecting survival, it does not meet statistical significance. PC-ALCL is a rare malignancy predominantly affecting older white male in the United States. The increased age is highly correlated with disease development, however, neither the demographic characteristics nor the site of the primary tumor affects the outcome for the patients. [N A J Med Sci. 2024;17(1):004-007.   DOI:  10.7156/najms.2024.1701004

An Incidental Large Rectal Polyp with Idiopathic Small Arteriovenous Dysplasia in Colonic Submucosa: A Case Report

Rectal polyps with idiopathic small arteriovenous dysplasia are rare. The mesenteric vascular diseases were recently classified as two vascular diseases: fibromuscular dysplasia (FMD) of artery and mesenteric arteriovenous dysplasia/vasculopathy (MAVD/V). FMD usually involves medium size mesenteric arteries in younger individuals. In contrast, MAVD/V tends to affect multiple small mesenteric arteries and veins without vascular lesions in other organs. We reported that a 45-year-old male with a large rectal polyp for routine colorectal screening. Microscopic examination shows chronic ischemic changes and multiple small arteries, veins and capillaries with intimal and medial hyperplasia and focal occlusion, mimicking mesenteric arteriovenous dysplasia and named it as submucosal arteriovenous dysplasia. [N A J Med Sci. 2024;17(1):001-003.   DOI:  10.7156/najms.2024.1701001

Vague Respiratory Symptoms as the Initial Presentation of Primary Cardiac Angiosarcoma: A Case Report

Primary cardiac angiosarcoma is a rare and aggressive tumor. Its symptoms and signs are often diverse and nonspecific, often leading to delayed diagnosis. Here we report a case of primary cardiac angiosarcoma with vague respiratory symptoms as the first presentation, possibly due to pulmonary metastasis.   The patient is a 58-year-old woman with shortness of breath for several weeks.  She further developed a dry nonproductive cough. Other symptoms include diarrhea, nausea and vomiting, fever, and fatigue.  Her past medical history included ankylosing spondylitis, fibromyalgia, hypertension, and tobacco use. Chest CT without contrast showed numerous bilateral pulmonary nodules scattered throughout her lungs. The main clinical differential diagnosis includes infectious endocarditis with septic pulmonary emboli or other possible multifocal infections. However, a computed tomography angiography (CTA) showed no evidence of pulmonary embolic disease. After being admitted into the hospital, a 2-dimensiomal echocardiogram was performed, revealing a sessile ovoid mass in the right atrium measuring 3.5 x 4.3 cm. MRI confirmed the above findings.   A CT-guided left lower lobe lung biopsy was performed, revealed lung parenchyma with areas of vascular proliferation lined by atypical cells showing high nuclear/cytoplasmic ratio, hyperchromatic nuclei, and frequent mitosis. These atypical cells are positive for CD31 and CD34, consistent with endothelial origin. TTF-1, CK7, CAM5.2, and CAMTA1 were all negative. Subsequently, a right atrial biopsy was also performed, showing scant neoplastic cells with significant nuclear atypia, frequent mitotic figures, and frequent intracytoplasmic vacuoles. The neoplasm appeared to be forming vaguely vascular spaces in a few minute areas combined with a diffuse pattern of growth, consistent with a neoplasm of vascular origin. Similar to the lung biopsy, neoplastic cells from right atrium are strongly positive for CD31, focal positivity for CD34, and negative for TTF-1, BER-EP4, MOC-31, CK5/6, calretinin, and HHV8. In addition, MIB-1 expression showed a high proliferative index. CAMTA immunostaining for epithelioid hemangioendothelioma was also negative. Based on the overall clinical, radiological, histological and immunohistochemical features, a final diagnosis of cardiac angiosarcoma with multifoci of lung metastasis was made. Outside pathological consultations agreed with this diagnosis.   Because the clinical presentation of cardiac angiosarcoma can be variable and nonspecific, raising awareness that the vague respiratory symptoms as one of its first presentation can avoid delayed diagnosis. [N A J Med Sci. 2024;17(1):019-024.   DOI: 10.7156/najms.2024.1701019]   Key Words: Cardiac angiosarcoma, vascular neoplasm, lung metastasis, malignant tumo

A Unique Case of Chronic Myeloid Leukemia Relapsing as an Isolated Blast Phase in the CNS and Literature Review

Chronic myeloid leukemia (CML) is one of the most common hematologic malignancies characterized by the Philadelphia chromosome and pathogenic fusion protein BCR-ABL1. CML is considered a treatable malignancy with a favorable outcome. However, one of the familiar and often fatal sequelae of this disease, is when the chronic phase leukemia evolves into the blast phase in the peripheral blood or bone marrow, or in extramedullary proliferation of blasts with myeloid or less commonly lymphoid differentiation. Extramedullary blast phase of CML is a rare phenomenon. Here, we report a case of a patient with CML, BCR-ABL1–positive, who had achieved hematologic and cytogenetic remission, who presented with neurological symptoms including dizziness, weakness, and headache. An MR of the brain showed diffuse cerebral and cerebellar leptomeningeal enhancement, and small regions of parenchymal enhancement in the left frontal lobe. A brain biopsy of an area of leptomeningeal enhancement showed a leptomeningeal infiltrate of blasts and immature myeloid cells, weakly positive for myeloid markers such as myeloperoxidase, CD117 and CD68, and was negative for CD3, PAX-5 and CD20. Fluorescent in-situ hybridization performed using dual fusion was positive for BCR-ABL1 translocation in the leptomeningeal infiltrate, indicative of a t(9;22) involving these two genes. The patient is being treated with intrathecal chemotherapy at the time of this report. This case documents an unusual presentation of known sequelae of CML. Awareness of this phenomenon will help us diagnose and manage this complication in the future.[N A J Med Sci. 2023;16(1):014-018.   DOI:  10.7156/najms.2023.1601014]  Key Words: Chronic myeloid leukemia, Blast crisis, Acute leukemia, Blood cancer, Malignanc