Multifocal Nodular Lesions Research Articles

LGG-24. DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR MANAGEMENT AND OUTCOME: A SINGLE CENTER EXPERIENCE

Abstract Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare diagnosis that was first incorporated into the WHO Classification in 2016. DLGNTs are usually low-grade tumors, with no current standard of care. A retrospective review of patients with a histologic diagnosis of DLGNT, from 2010 to 2022, was done with IRB approval. Eight patients were identified with a median age at diagnosis of 5.5 years (range 4 months - 21 years). Imaging findings included diffuse leptomeningeal enhancement and multifocal nodular lesions in the supratentorial and infratentorial locations. One patient had localized pineal disease and 2 patients had isolated spinal cord involvement. Histologically, 6/8 (75%) patients showed low-grade tumor (Ki-67 index = 2-15%). BRAF-KIAA1549 fusion was reported in 3, NTRK fusion in 1, PTPN11 mutation in 1, and FGFR1 mutation in 1 patient. Seven patients (88%) were treated with proton radiation, 3 at diagnosis and 4 upon progression. Chemotherapy was used at diagnosis on 4 patients (temozolomide, carboplatin and vincristine, and vinblastine). Targeted therapy (NTRK or BRAF-inhibitors) was utilized upon progression in four patients, and at diagnosis in one. All patients showed disease progression at a median time of 24 months from diagnosis. The median progression-free survival (PFS) in the group receiving upfront RT was 2.2 years (range = 0.4 – 6.6 years), versus chemotherapy of 1.4 years (range = 0.15 - 2.6 years) The 2 years PFS and OS are 57% and 100%, respectively. At a median follow-up of 4.5 years (range = 3 months to 9 years), 6 patients have stable disease (of whom 2 are off therapy), and 2 patients have progressive disease. DLGNTs are rare tumors with scarce data about radiological and molecular characteristics, and no established standard of care. Our case series emphasizes the need for further studies on molecular profiling and exploring targeted therapies.

Outbreak of Yersinia pseudotuberculosis in capybaras (Hydrochoerus hydrochaeris) kept in captivity

On January 2020, an outbreak of acute mortality was detected in the capybara (Hydrochoerus hydrochaeris) population kept in the Cordoba Zoo Conservation Center (CZCC) in Spain. Morbidity and mortality rates were 71%, and the fatality rate was 100%. Macroscopic examination revealed multifocal nodular lesions with fibrinonecrotic exudate in lungs and mesenteric lymph nodes. Microscopic lesions were characterized as severe acute fibrinopurulent bronchopneumonia and generalized vascular changes. Cultures and biochemical analyses yielded Yersinia pseudotuberculosis (YPT). This species was confirmed by both PCR and MALDI-TOF. This report describes the first outbreak of fatal YPT infection in zoo animals in Spain and confirms that capybaras are highly susceptible to this pathogen, which could be of animal health, conservation, and public health concern. Future studies are warranted to determine potential sources of YTP infection in zoos to prevent future cases in susceptible species, including humans.

Neonatal Sudden Death Due to Histiocytoid Cardiomyopathy

Histiocytoid cardiomyopathy, an extremely rare heart disease in infants and children, usually occurring in girls under the age of 2 years, is characterized by cardiomegaly, ventricular arrhythmia, and sudden death. In the present study, we report a case of a 2-day-old female neonate who suddenly showed cyanosis and cardiac arrest in the neonatal unit and died without resuscitation. Autopsy revealed multifocal nodular lesions in the left ventricle wall and papillary muscles. Microscopically, these lesions were composed of discohesive round or polygonal cells with eosinophilic cytoplasm and were positive for desmin and negative for CD68. Electron microscopy findings displayed abnormal swollen mitochondria with disorganized cristae, dense granules, and diminished myofibrils in the periphery of the cytoplasm.

Canine Synovial Sarcoma of the Stifle Joint with Pulmonary and Liver Metastases

A seven-year-old female mongrel dog was presented at the Sokoine University of Agriculture Teaching Animal Hospital for second opinion regarding a progressive swelling of the right hind limb of two months duration. Clinical examination revealed a loss of body condition, tachypnea and tachycardia, a painful immobile solid mass of 20 cm x 14 cm x 10 cm located on the right stifle joint, leucocytosis, and anaemia. Radiographic examination of the joint revealed marked soft tissue swelling with amorphous areas of mineralization and complete destruction of the proximal tibia. Smooth and solid periosteal reaction was seen around the tibia and fibula with a Codman’s triangle. Multiple nodules and a mass with soft tissue opacity were seen in the lung fields. Post-mortem examination revealed separation of tibia and fibula, softening of the proximal parts of the tibia, and complete integration of the proximal region of the two bones and articular tissues into the surrounding muscular tissues. Multifocal nodular lesions of variable sizes were mostly found in the lungs and partly in the liver. Histologically, predominantly oval and round cells with variable nuclear sizes and moderate mitoses were observed in tissue samples from the joint, lungs and the liver although some parts of the lung metastases showed both round and spindle shaped tumor cells. Clinical profile is suggestive of aggressive biphasic (spindle and epithelial) type of synovial cell sarcoma with lung and liver metastasis. Early radiographic and biopsy examination of persistent musculoskeletal nodules is recommended for early diagnosis and interventions.

Disseminated Langerhans cell histiocytosis presenting as oesophageal disease in a cat

Case summaryAn 11-year-old female spayed domestic shorthair cat was referred with a 2-month history of ptyalism, hyporexia and weight loss. Physical examination revealed reduced body condition score (2/9) and decreased skin turgor. Laboratory abnormalities included mild erythrocytosis, elevated creatine kinase, hypercobalaminaemia and hypofolataemia. CT of the head and abdominal ultrasonography were within normal limits. Gastroesophagoscopy revealed mucosal ulceration and possible stenosis of the distal oesophagus. Thoracic radiographs and iodine oesophagram showed a soft tissue opacity in the caudodorsal thorax compatible with a parietal oesophageal mass causing luminal stenosis or an extra-parietal mass causing ventral displacement and compression of the oesophagus. Pulmonary nodules were observed in the cranial lung lobes. CT of the thorax confirmed the oesophageal origin of the mass and the presence of pulmonary nodules scattered throughout the lung parenchyma. The patient was euthanased given the imaging findings and perceived guarded prognosis. Post-mortem examination revealed multifocal nodular lesions affecting the oesophagus, lungs, kidneys and pancreas. Histopathological examination identified atypical round cells characterised by eosinophilic cytoplasm and pale nuclei with prominent nuclear grooves, compatible with neoplastic histiocytic cells. Immunohistochemistry revealed strong expression for CD18, Iba-1 and vimentin. Transmission electron microscopy demonstrated intracytoplasmic organelles consistent with Birkbeck granules of Langerhans cell origin in lesional histiocytes. These findings were compatible with a diagnosis of disseminated Langerhans cell histiocytosis.Relevance and novel informationTo our knowledge, this is the first report of disseminated Langerhans cell histiocytosis with oesophageal involvement in a cat.

Intra-abdominal Aspergillosis due to Aspergillus fumigatus in a Dog

A 3 year-old, spayed female, mixed-breed dog presented with abdominal distension due to a large mass, detected during abdominal palpation and confirmed by abdominal imaging. Cytological examination of the mass was suggestive of pyogranulomatous inflammation. During exploratory laparotomy, extensive peritoneal adhesions and multifocal nodular lesions on the liver, spleen and omentum were revealed. One week later, the dog deteriorated and was euthanized. Numerous firm masses were observed in the liver, spleen, left kidney, stomach, small and large intestine during necropsy. The lungs, heart, and ocular structures were macroscopically normal. Histopathology results (surgery and necropsy) revealed fungal hyphae enclosed in the pyogranulomatous lesions. Polymerase chain reaction (PCR) products showed 100% homology with Aspergillus fumigatus and agar gel double diffusion was positive for IgG antibodies against the same fungus.

Nonlinear tumor evolution from dysplastic nodules to hepatocellular carcinoma.

Dysplastic nodules are premalignant neoplastic nodules found in explanted livers with cirrhosis. Genetic signatures of premalignant dysplastic nodules (DNs) with concurrent hepatocellular carcinoma (HCC) may provide an insight in the molecular evolution of hepatocellular carcinogenesis. We analyzed four patients with multifocal nodular lesions and cirrhotic background by whole-exome sequencing (WES). The genomic profiles of somatic single nucleotide variations (SNV) and copy number variations (CNV) in DNs were compared to those of HCCs. The number and variant allele frequency of somatic SNVs of DNs and HCCs in each patient was identical along the progression of pathological grade. The somatic SNVs in DNs showed little conservation in HCC. Additionally, CNVs showed no conservation. Phylogenetic analysis based on SNVs and copy number profiles indicated a nonlinear segregation pattern, implying independent development of DNs and HCC in each patient. Thus, somatic mutations in DNs may be developed separately from other malignant nodules in the same liver, suggesting a nonlinear model for hepatocarcinogenesis from DNs to HCC.

Development of multifocal nodular lesions of a liver mimicking hepatic metastasis, following resection of an insulinoma in a child.

Insulinoma, which arises from insulin-producing pancreatic beta cells, is a rare tumor in children. Only 5%-10% of insulinomas are malignant and undergo metastasis. We report a case of an 11-year-old girl who experienced hypoglycemia-related seizures induced by an insulinoma; after resection of the primary tumor, she developed hepatic focal nodular hyperplasia (FNH). Laboratory test results indicated marked hypoglycemia with hyperinsulinemia. Abdominal ultrasonography (US) and computed tomography results were normal; however, magnetic resonance imaging (MRI) showed a solid mass in the pancreatic tail. Therefore, laparoscopic distal pancreatectomy was performed. Two months after the surgery, an abdominal MRI revealed multiple nodular lesions in the liver. An US-guided liver biopsy was then performed, and histological examination revealed FNH without necrosis or mitotic activity. The patient has been free of hypoglycemia for 2 years, and recent MRI studies showed a decrease in the size of FNH lesions, without any evidence of metastasis. Even though no metastatic lesions are noted on imaging, close observation and follow-up imaging studies are required in a child with insulinoma that has malignant potential on histopathologic findings.

Malignant Uveal Schwannoma With Peripheral Nerve Extension in a 12-Week-Old Color-Dilute Labrador Retriever

The formalin-fixed, amber-colored right globe from a 12-week-old female silver Labrador Retriever dog was submitted to the Comparative Ocular Pathology Laboratory of Wisconsin for light microscopic evaluation. The clinical history described a collapsed anterior chamber and multifocal nodular lesions in the peripheral iris. Histologically, immunohistochemically, and ultrastructurally, the uveal mass was consistent with a malignant schwannoma; there was extension along peripheral nerves within the sclera. The signalment and behavior of the neoplasm distinguish it from the uveal schwannoma of blue-eyed dogs and bear some resemblance to the ocular lesions in human neurofibromatosis. The dilute color mutation may contribute to the cause. Six weeks later, the dog did not develop any additional masses.

Pulmonary toxocariasis masquerading as metastatic tumor nodules in a child with osteosarcoma

A 14-year-old male, who completed chemotherapy following limb salvage surgery for osteosarcoma approximately 2 years ago, was seen for routine follow-up. A CT scan revealed new scattered multifocal nodular lesions. An ultrasonography-guided percutaneous needle biopsy was done to confirm pulmonary metastasis of the underlying osteosarcoma. The lung biopsy showed findings of eosinophilic pneumonia with no evidence of malignancy. Peripheral eosinophilia was also noted. When a more thorough history revealed frequent intake of raw cow liver, we diagnosed pulmonary toxocariasis by ELISA for specific serum IgG antibody.

Multifocal Abrikossoff's granular cell tumor of the oesophagus: Case report

Granular cell tumours, relatively uncommon soft tissue tumours, have been a matter of debate among pathologists regarding histogenesis for a long time. Less common locations are in the aerodigestive tract including the oesophagus. We have recently treated a rare case, a 37-year-old male, who was admitted due to dysphagia and a painful swallow with occasional pharyngo-nasal regurgitation followed with a mild loss of weight. Standard clinical examination including X-ray chest, ECG and laboratory tests did not show pathological findings. Barium contrast oesophagography demonstrated multiple ovoid defects in the wall of the oesophagus. CT scan of the chest confirmed luminal narrowing owing to the tumour of the upper oesophagus. Upper endoscopy showed unusual multifocal nodular lesions alongside the oesophageal axis covered by smooth mucosa. A primary biopsy specimen taken from the largest nodules confirmed an unusual pathological finding of the granular cell tumour. Subtotal, transpleural oesophagectomy was performed and reconstruction was derived by long colon segment interposition through the posterior mediastinum. The postoperative course was uneventful. The operative specimen consisted of four ovoid tumours alongside the oesophagus (the greatest diameter 0.5-1.8, average 1.25). All verified tumours histologicaly consisted of a spindle-shaped or polygonal cells containing small and large eosinophilic granules and central nuclei. Most tumour cells showed strongly positive immunohistochemical staining for S-100 protein. These tumour cells were partially positive for p-53 and Ki-67. No lymph node metastases were detected histologically. Multifocal granular cell tumour of the oesophagus is an unusual finding with low incidence, and rarely caused symptoms. Pathological features and multiplicity of such tumours emphasized malignant predisposition requiring surgical resection of the oesophagus.

Epstein–Barr virus-associated T/NK cell-type central nervous system lymphoma which manifested as a post-transplantation lymphoproliferative disorder in a renal transplant recipient

A 31-year-old male, who had received a cadaveric renal allograft in April 2003, consulted a clinic for a transient hemiplegia in August 2004. At that time, a course observation without medication was chosen. In October 2004, he was admitted to our hospital by ambulance with a clonic seizure and a recurrence of hemiplegia on the right side of his body. Head magnetic resonance imaging (MRI) showed enhanced multifocal nodular lesions with remarkable cerebral edema mainly in the left frontal lobe. A stereotactic brain biopsy was performed, and the pathological diagnosis was nasal type extranodal T/NK cell lymphoma manifested as the post transplant lymphoproliferative disease (PTLD). Systemic staging workups showed no extra-CNS involvement. Because of his renal dysfunction and no sign of any extra-CNS involvement, a reduction of the immunosuppressants and whole brain radiation therapy (WBRT) (40 Gy) without chemotherapy were applied to his therapeutic regimen. After WBRT, MRI showed a remarkable reduction in the number and size of the tumors, and no neurological abnormalities were physically observed. As of December 2006, no sign of recurrence has subsequently been found in both the intra- and extra-CNS.

Multifocal Nodular Non-Alcoholic Steatohepatitis (NASH)

Introduction: Insulin sensitizers have been reported to improve liver biochemistry and histology in patients with NASH. Rarely fatty lesions in liver can be multifocal and nodular, and mimic metastatic disease to the liver. We describe a patient with multifocal nodular NASH who's radiological and biochemical abnormalities resolved with rosiglitazone. Case: A 59-year-old white female with metabolic syndrome underwent CT scan of her liver to evaluate abnormal transaminases. This revealed a hypodense mass with a size of 10.5 cm in maximum diameter in left lobe with multifocal nodular lesions in the right lobe of liver. This was initially concerning for malignant disease. However MRI suggested multifocal nodular fatty liver. A laparoscopic liver biopsy was nevertheless elected. The liver surface had yellowish discoloration with fibrotic changes. Biopsy showed changes consistent with NASH and early fibrosis. The patient was started on vitamin E 400 IU daily. At 6 months there was no change in CT scan findings. Rosiglitazone 4 mg twice a day was added and vitamin E was continued. Six months later her hemoglobin A1C improved from 6.7% to 6.1%. Her fasting glucose and insulin levels improved. She was able to improve her body mass index from 29.3 to 26.6. Transaminases normalized. A repeat CT scan done after 6 months of rosiglitazone showed resolution of multifocal nodular fatty liver lesions. Conclusion: This case illustrates that multifocal nodular fatty liver can mimic metastatic disease to the liver. Rosiglitazone resulted in improvement in insulin resistance and dramatic resolution of nodular fatty lesions on CT scan.

Coexpression of multiple Sertoli cell and Leydig cell marker genes in the spontaneous testicular tumor of F344 rat: evidence for phenotypical bifurcation of the interstitial cell tumor.

The development of testicular tumor has been frequently observed in some laboratory rat strains. In the present study, we have further characterized the testicular tumor that spontaneously develops in the F344 rat (F344/Jcl). Tumor cells first appeared in the interstitium and developed into multifocal nodular lesions. In the later stage, the whole testes were occupied by tumor cells that consisted of three different types of cells in morphological appearance: large clear type, small eosinophilic type and intermediate type. To determine the character of these cells, we examined the expression of marker genes for Sertoli cells (e.g., transferrin) and Leydig cells (e.g., 3β–hydroxysteroid dehydrogenase 1 (3β–HSD 1)). Transferrin and 3β–HSD 1 mRNAs were found in all 8 tumor samples analyzed hy northern blotting. By in situ hybridization, we observed a substantial amount of 3β–HSD 1 mRNA and little or no transferrin mRNA in the large clear cells. In contrast, the small eosinophilic cells showed little or no 3β–HSD 1 mRNA and a large amount of transferrin mRNA, suggesting that the tumor was a mixture of at least two types of cells. Other Sertoli cell marker genes, such as cyclic protein 2 and sulfated glycoprotein 2, were expressed in all 8 tumors analyzed, and testin and steel factor (SLF), the c–kit receptor ligand, were also expressed in some of the tumors (testin, 75%; SLF, 25%), while other Leydig cell markers, LH receptor and c–kit, were expressed in 87% and 80% of the tumors, respectively. These results indicate that the spontaneous testicular tumor of F344 rat is of interstitium origin, showing phenotypical bifurcation possibly via transdifferentiation.

Role of MRI in diagnosis of childhood sarcoidosis with fever of unknown origin.

Childhood sarcoidosis is a disease with multisystem organ involvement, and initial presentation as fever of unknown origin (FUO) is relatively common. We describe herein three children (aged 9, 7, and 11 years) with sarcoidosis who were seen initially with FUO. Common clinical and laboratory features include fever of > 2 weeks' duration, weight loss, fatigue, leg pain, anemia, increased erythrocyte sedimentation rate, elevated immunoglobulin G level, negative antinuclear antibodies and rheumatoid factor, and negative purified protein derivative and Candida skin tests. Two patients had iridocyclitis, one had hilar adenopathy, and two had angiotensin-converting enzyme serum levels. All three had no evidence of pulmonary infiltrates on chest radiographs. Bone marrow biopsies for all three were normal, and with no evidence of malignancy. Plain radiographs of the lower extremities and bone scan were normal. Magnetic resonance imaging (MRI) of the lower extremities revealed intact bone architecture and multifocal nodular lesions within the marrow. Bone biopsy from the tibia performed on two patients showed normal bone trabeculae and a solitary noncaseating epithelioid cell granuloma. Noncaseating granuloma was found on reevaluation of the bone marrow biopsy in the third patient. All three patients had negative marrow stains and cultures for fungi and mycobacteria. We conclude that MRI was very useful in the diagnosis of sarcoidosis in children with FUO.

Multifocal Pulmonary Lesions of Possible Decidual Origin (So-called Pulmonary Deciduosis): Report of a Case

Roentgenographic studies revealed multifocal nodular lesions within the lungs of a 28-year-old woman who also had a ruptured tubal pregnancy. Pulmonary biopsy studies revealed the lesions to be decidua-like. Hematogenous metastasis from the placental site during an earlier pregnancy is favored over other possibilities for origin of the tissue. However, the possibility that the patient had a peculiar form of pulmonary tumor has not been entirely excluded. The patient has been observed for 5 years postoperatively and has remained asymptomatic, although the pulmonary lesions have remained stabilized as determined by follow-up roentgenographic studies.