Multinodular Tumor Research Articles

Malignant Esophageal Glomus Tumor With CARMN::NOTCH2 Fusion: An Additional Tumor Underscoring the Frequent Tendency of Esophageal Glomus Tumors for Aggressive Behavior

Malignant glomus tumors are rare tumors of pericytic origin with a propensity to develop in the upper gastrointestinal tract. Hereby we demonstrate a tumor of a 20-year-old man, who presented with dysphagia and an exophytic esophageal mass. Histologic examination of the resected mass revealed a multinodular tumor in the esophageal wall composed of epithelioid cells showing nesting and monomorphic atypia, staghorn vessels and scanty stroma. Immunohistochemically, the neoplastic cells were positive for SMA, and H-caldesmon, while desmin was negative. Collagen IV and laminin decorated a dense intercellular basal membrane meshwork. RNA-sequencing using TruSight RNA Pan-Cancer Panel revealed a CARMN::NOTCH2 fusion, that is a recurrent, frequently described and so far specific genetic alteration in glomus tumors. In spite of the adjuvant chemotherapy regimens, the patient died of disseminated metastatic disease 2 years after the diagnosis. Our patient presentation and the previous reports in the literature highlight the frequently aggressive behavior of glomus tumors arising in the esophagus.

A Case Report of Follow-up about a Yorkshire Dog with Multinodular Bone Tumor with Development of Pulmonary Metastasis

The multinodular bone tumor is a slow-growing, locally invasive malignant tumor capable of metastasizing. Its occurrence is greater in the flat bones of the skull and hard palate. The clinical signs depend on the location of tumor and are generally related to compression of adjacent structures. This report describes the follow-up of a case of multinodular bone tumor in a currently thirteen-year-old dog, Yorkshire Terrier breed, which was initially treated with neoformation in a region overlapping the topography of the left zygomatic arch and the caudal portion of the left mandibular branch. After performing a skull radiographic evaluation, computed tomography and laboratory investigation, surgical removal and histopathological examination were performed, which confirmed the suspicion of a multinodular bone tumor. Two years after surgery, pulmonary metastasis was found on the left side of the lung. At the time of this publication, the animal is in good general condition and without respiratory symptoms, despite progressive metastatic growth.

Surgical treatment of chondromyxoid fibroma of ribs via thoracoabdominal access

Surgical treatment of chondromyxoid fibroma of ribs is described. The diagnosis was verified after histological analysis. The patient underwent resection of multinodular tumor of anterolateral thoracic wall invading abdominal cavity via thoracoabdominal access. Postoperative period was uneventful. This case demonstrates the need for total en-bloc resection of tumor with surrounding tissues. Surgery is the only effective method for these patients.

Primary lipoblastic nerve sheath tumor in an inguinal lymph node mimicking metastatic tumor: a case report and literature review

Lipoblastic nerve sheath tumors of soft tissue are characterized as schwannoma tumors that exhibit adipose tissue and lipoblast-like cells with signet-ring morphology. They have been documented to arise in various anatomic locations, including the thigh, groin, shoulder, and retroperitoneum. However, to our knowledge, this tumor has not been previously reported as a lymph node primary. We present herein the first case of a benign primary lipoblastic nerve sheath tumor arising in an inguinal lymph node in a 69-year-old man. Microscopic examination revealed a multinodular tumor comprising fascicles of spindle cells, as well as adipocytic and lipoblast-like signet-ring cell component in the context of schwannoma. Despite the presence of some bizarre cells with nuclear atypia, no obvious mitotic activity or necrosis was observed. Immunohistochemical analysis showed strong and diffuse expression of S-100, SOX10, CD56, and NSE in the spindle cells as well as in the signet-ring lipoblast-like cells and the mature adipocytes. Sequencing analysis of the neoplasm identified six non-synonymous single nucleotide variant genes, specifically NF1, BRAF, ECE1, AMPD3, CRYAB, and NPHS1, as well as four nonsense mutation genes including MRE11A, CEP290, OTOA, and ALOXE3. The patient remained alive and well with no evidence of recurrence over a period of ten-year follow-up.

Surgical management of sporadic and schwannomatosis-associated pelvic schwannomas.

Pelvic schwannomas are rare tumors that may occur either sporadically or in the context of schwannomatosis. We retrospectively reviewed the charts of patients harboring a pelvic schwannoma under conservative management or operated at our reference center between 2016 and 2023. All patients were operated by a multidisciplinary team, combining a vascular surgeon and a neurosurgeon. Twenty-four patients harboring 33 pelvic tumors were included in the cohort, including 12 patients with sporadic lesions, 2 patients with NF2-related schwannomatosis, and 10 patients with NF2-independent schwannomatosis. Multi-nodular tumors were more frequent in schwannomatosis compared to sporadic cases (p = 0.005). The mean age at diagnosis was 41years old. Schwannomas were located on branches of the sciatic nerve (23/33, 70%), the femoral nerve (6/33, 18%), and the obturator nerve (4/33, 12%). Over the course of the study, 16 patients were operated, including 11 sporadic cases. The indication for surgery was pain (12/16, 75%) or tumor growth (4/16, 25%). Complete resection was achieved in 14 of 16 patients (87%). The mean post-operative follow-up was 37months (range: 2-168months). At last-follow-up, complete pain relief was achieved in all 12 patients with pre-operative pain. Post-operative morbidity included 3 long-term localized numbness and one MRC class 4 motor deficit in a multi-nodular tumor in a schwannomatosis patient. Despite its limited size, our series suggests that nerve-sparing resection of pelvic schwannomas offers satisfying rates of functional outcome both in sporadic and schwannomatosis cases, except for multi-nodular tumors.

Proximal epithelioid sarcoma of the vulva. A rare neoplasm. A clinicopathological case

Epithelioid sarcoma is a rare aggressive soft tissue sarcoma, which can be distal or proximal types. The classic form (distal-type) of epithelioid sarcoma mainly occurs in teenagers and young adults. A rarer form, called large-cell (proximal-type) epithelioid sarcoma, tends to be more aggressive and mainly affects adults. The proximal subtype mostly arises from the proximal pelvis, limbs, and genital tract. We report a case of a 59 -year-old female, presented with a progressively growing mass in the left labia majora. Gynecologic examination revealed a 2 cm mobile and painless mass that was not attached to deep planes. The histological study showed a multinodular tumor was seen comprising sheets of oval to polygonal cells with moderate amount of cytoplasm. Interspersed were larger, rhabdoid cells with abundant eosinophilic cytoplasm and prominent nucleoli. On IHC, the tumor cells showed positivity for EMA and CKAE1/AE3 and do not expressed INI-1 in the nucleus. All tumor cells were negative for S-100 protein and CD34. The histopathological diagnosis was soft tissue of the vulvar region with proximal epithelioid sarcoma. The patient received adjuvant external pelvic radiotherapy and brachytherapy in the vulvar bed. Currently, 3 years after diagnosis, the patient does not present signs of tumor recurrence in her controls. Due to its low incidence, there are no evidence-based diagnostic algorithms or published recommendations for treatment. The prognosis is generally poor. A wide excision with clear margins is imperative with options of post-operative CT/RT in individual cases during a close follow-upbehavior, as seen in our case.

Plexiform Schwannoma of Digital Nerve.

Plexiform schwannoma is an uncommon benign tumour that grows in a plexiform pattern. We report a 47-year-old man with a mass on the palmar aspect of the metacarpophalangeal joint of the right index finger that had been growing gradually for more than 10 years. The mass was palpated from the distal carpal tunnel to the ulnar aspect of the proximal interphalangeal joint of the index finger, with tingling and numbness sensation. The tumour was a multinodular tumour involving the first common palmar digital nerve to the ulnar proper palmar digital nerve. It was resected and reconstructed with a sural nerve graft. Plexiform schwannoma is rare in the digital nerve, with only six cases reported. Generally, classic schwannomas can be enucleated without causing neurologic deficits; however, plexiform schwannoma may require nerve resection. There have been reports of recurrence of plexiform schwannoma; definitive resection and long-term follow-up are necessary. Level of Evidence: Level V (Therapeutic).

Multinodular gastro intestinal stromal tumor in small intestine with perforation and Meckel’s diverticulitis- An unusual presentation

Gastrointestinal Stromal tumor are rare group of mesenchymal neoplasms originating from the wall of the digestive tract. Outcome strongly dependent on tumor size and mitotic activity. A 60-year male presented with abdominal pain and distention for 3 months. After initial evaluation, emergency laparotomy was done. Intraoperatively found to have multiple small nodules in peritoneum and mesenteric border of small intestine and rupture of a big nodule was observed causing peritonitis. Gross examination-Multiple nodular tumour mass in small intestine along with multiple haemorrhagic nodule of varying size seen in mesentry. Tumor arising from muscular layer arranged in interlacing fascicles, bundles, whorls and sheets. Tumor cells are elongated having spindle to elongated nucleus with vesicular to dense chromatin and inconspicuous nucleoli. Some of the nodules shows areas of haemorrhage and necrosis. Mitotic figure > 5/50 HPF seen. Histological grade-G2 High grade >5/50 HPF, TNM grade-PT4PNxPMx. Immunohistochemistry-Diffusely Positive for CD117. Focally positive for DOG1, CD34 & SMA. Small intestinal GISTs comprise approximately 30% of all GISTs. Tumor size vary from small nodules to complex masses of around 20 cm. GIST is more common in patients with age >40 years. CD117 and DOG1 positivity are used to define these tumors. Novelty: Only few cases has been reported in small bowel GIST with perforation and multiple nodules.

Clinicopathological and molecular features of multinodular and vacuolating neuronal tumors of the cerebrum

Objective: To investigate clinicopathological features of multinodular and vacuolar neurodegenerative tumor (MVNT) of the cerebrum, and to investigate its immunophenotype, molecular characteristics and prognosis. Methods: Four cases were collected at the General Hospital of Southern Theater Command, Guangzhou, China and one case was collected at the First People's Hospital of Huizhou, China from 2013 to 2021. Clinical, histological, immunohistochemical and molecular characteristics of these five cases were analyzed. Follow-up was carried out to evaluate their prognoses. Results: There were four females and one male, with an average age of 42 years (range, 17 to 51 years). Four patients presented with seizures, while one presented with discomfort on the head. Pre-operative imaging demonstrated non-enhancing, T2-hyperintense multinodular lesions in the deep cortex and superficial white matter of the frontal (n=1) or temporal lobes (n=4). Microscopically, the tumor cells were mostly arranged in discrete and coalescent nodules primarily within the deep cortical ribbon and superficial subcortical white matter. The tumors were composed of large cells with ganglionic morphology, vesicular nuclei, prominent nucleoli and amphophilic or lightly basophilic cytoplasm. They exhibited varying degrees of matrix vacuolization. Vacuolated tumor cells did not show overt cellular atypia or any mitotic activities. Immunohistochemically, tumor cells exhibited widespread nuclear staining for the HuC/HuD neuronal antigens, SOX10 and Olig2. Expression of other neuronal markers, including synaptophysin, neurofilament and MAP2, was patchy to absent. The tumor cells were negative for NeuN, GFAP, p53, H3K27M, IDH1 R132H, ATRX, BRG1, INI1 and BRAF V600E. No aberrant molecular changes were identified in case 3 and case 5 using next-generation sequencing (including 131 genes related to diagnosis and prognosis of central nervous system tumors). All patients underwent complete or substantial tumor excision without adjuvant chemoradiotherapy. Post-operative follow-up information over intervals of 6 months to 8 years was available for five patients. All patients were free of recurrence. Conclusions: MVNT is an indolent tumor, mostly affecting adults, which supports classifying MVNT as WHO grade 1. There is no tumor recurrence even in the patients treated with subtotal surgical excision. MVNTs may be considered for observation or non-surgical treatments if they are asymptomatic.

Imaging Features of Lymphoepithelial-Like Carcinoma of the Salivary Glands.

Lymphoepithelial-like carcinoma of the salivary glands (LELCSG) is a rare tumour of unknown aetiology. No studies have reported the imaging features of primary LELCSG. The clinical information and imaging features of eight patients with LELCSG were reviewed. Computed tomography (n = 4 patients) and magnetic resonance imaging (n = 4 patients) features were analysed by two radiologists to identify the location, number, size, shape, boundary, signal intensity and enhancement of LELCSG. The study included four women and four men, and the mean size of the tumours was 32.88 ± 3.41 mm (range, 27-38 mm). The tumours affected the parotid gland in six cases and the submandibular gland in two cases. The eight cases were evaluated by radiologists. All tumours were lobulated; three had clear edges and five had blurred edges. There was no necrosis in six tumours, while two tumours exhibited slight necrosis without bleeding. All eight tumours showed multiple nodular changes and extensive fusion. Four tumours with magnetic resonance imaging (MRI) were isointense or slightly hyperintense on T1-weighted imaging (T1WI) and obvious homogeneous enhancement on contrasted enhanced T1WI scan, while slightly hyperintense on T2-weighted imaging (T2WI). The other four lesions were isodense on computed tomography (CT) scan. The degree of enhancement varied among the eight tumours. The necrotic zones of the eight tumours did not exhibit any enhancement. LELCSG is a lobulated, multi-nodular tumour, with some fused nodules. LELCSG lesions showed isointensity or slight hyperintensity on T1WI MRI, slight hyperintensity on T2WI MRI and isodense on CT scan. Larger tumours may exhibit some necrosis, but the necrotic cysts were relatively rare. Uniform enhancement was observed in non-necrotic areas on enhanced CT and MRI scan. The multi-nodular feature may be valuable for diagnosis.

Giant cell tumor of soft tissue of the colon: a case report and review of the literature

BackgroundA giant cell tumor (GCT) is a benign neoplasm characterized by mixture of mononuclear cells and multinucleated cells. A GCT of soft tissue (GCT-ST) is developed in various extraosseous sites, but GCT-ST of the gastrointestinal tract is very rare. GCT-ST usually has a benign course, but rare cases reported malignant potential of the tumor. Therefore, complete resection is required to prevent local recurrence or distant metastasis.Case presentationA 53-year-old woman was admitted for follow-up colonoscopy who underwent the colorectal endoscopic submucosal dissection (ESD) of a laterally spreading tumor at the hepatic flexure 6 months ago. A colonoscopy showed a polypoid mass about 3.5 × 2.5 cm at the previous ESD site. As endoscopic finding showed a smooth multi-nodular tumor without submucosal invasion, we performed endoscopic mucosal resection. Based on pathological and immunohistochemical findings, the lesion was diagnosed as a GCT-ST in the colon. Follow-up colonoscopy performed 6 months later revealed no evidence of recurrence.ConclusionThis is the first report of a GCT-ST identified in the colon. Although GCT-ST generally has a benign clinical course, complete resection should be performed to prevent local recurrence and metastasis.

Multimodal Treatment of Hepatocellular Carcinoma in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antivirals.

Background: Direct-acting antivirals (DAAs) opened a new era in the management of hepatitis C virus (HCV)-associated liver disease. However, hepatic cancer screening should not be stopped after obtaining a sustained virologic response (SVR). Current guidelines offer several treatment options for hepatocellular carcinoma (HCC), mainly depending on its stage and the extent of liver disease, including tumor resection, liver transplantation (LT), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and systemic agents. This article provides an overview of treatment modalities for hepatocellular carcinoma and associated survival rates based on the experience of the Internal Medicine Center at Fundeni Clinical Institute while bringing into light previous medical research.Methods: We included 59 patients with a personal history of hepatitis C virus infection, diagnosed with hepatocellular carcinoma at least one year after achieving a sustained virologic response through direct-acting antivirals. The albumin-bilirubin (ALBI) score and Barcelona Clinic Liver Cancer (BCLC) classification were assessed in each case, and all patients were treated accordingly. The subjects were monitored by liver function tests, tumor markers, blood cell count, coagulation profile, and imaging explorations. We investigated the Eastern Cooperative Oncology Group (ECOG) performance status, the response to applied treatments, and survival.Results: Cirrhotic patients and multinodular tumor patterns were predominant. Most patients only experienced one therapeutic procedure, while the rest of the study group went through multiple treatment modalities (2-4), with a better outcome in terms of survival parameters. A large proportion presented with disease progression despite the therapeutic measures applied. A total of two liver transplants were performed, resulting in a 12-month disease-free period among these patients. The presence of diabetes mellitus (DM), multinodular disease, alpha-fetoprotein (AFP) over 300 ng/mL, and tumor dimension over 6 cm indicate poor overall survival. Both overall survival and progression-free survival were better in subjects who presented complete responses (CR) to HCC treatment. In patients undergoing a single intervention, the best overall survival was associated with surgical resection and RFA.Conclusion: The multimodal treatment of hepatocellular carcinoma represents the best approach, in order to maintain patients on the waiting list for liver transplantation. In hepatitis C virus infection, viral clearance is important to obtain. At the same time, particular attention should be paid to liver cancer screening even after obtaining a sustained virologic response.

A case of retroperitoneal tumor displaying epithelial differentiation, prominent myxoid stroma and loss of INI1/SMARCB1

SummaryThe clinicopathological spectrum of INI1 deficient tumors is expanding. Epithelioid sarcoma (ES) is a rare sarcoma of uncertain differentiation, more often occurring in the extremities and uncommonly in the deep soft tissues. Histopathologically, it manifests in the form of classical, proximal, or hybrid types, the latter two characterized by rhabdoid cytomorphology. Immunohistochemically, ESs display loss of INI1/SMARCB1 and genetically associated with high percentage of SMARCB1 deletionsWe report an extremely uncommon case of a retroperitoneal tumor in a 42-year-old male, who presented with abdominal discomfort. Radiologic imaging disclosed a 12 cm-sized retroperitoneal mass without involvement of any organ parenchyma. The patient underwent tumor excision with left-sided nephrectomy at another hospital. A review of the paraffin-embedded tissue sections revealed a multinodular tumor, composed of dyscohesive epithelioid tumor cells and focally arranged in cords, containing moderate to abundant, eosinophilic cytoplasm, vesicular nuclei, containing prominent nucleoli, including cells with rhabdoid cytomorphology, in a conspicuous myxoid stroma. A focal tumor area resembled proximal-type of ES. Immunohistochemically, tumor cells displayed positivity for pan cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), vimentin and focally for CA125, while these were negative for CD34, S100 protein, CKIT, DOG1, and INI1/SMARCB1.To the best of our knowledge, this constitutes the first case of a malignant tumor with epithelioid morphology, displaying myxoid matrix and loss of INI1/SMARCB1, resembling a myxoid variant of an epithelioid sarcoma and myoepithelioma-like tumor of the vulvar tumor, occurring in the retroperitoneum. A review of similar cases, differential diagnosis and treatment-associated implications are presented.

Angiosarcoma Secondary to Primary Upper Limb Lymphedema

Stewart–Treves syndrome (STS) is a rare entity with a poor prognosis defined as an angiosarcoma appearing in a specific clinical setting, in 90% of cases in a context of breast neoplasia. Herein, we report a rare case of STS of the upper limb as a complication of primary lymphedema. A 55-year-old male was referred for a large, reddish, necrotic multinodular tumor of rapid extension on the anterior aspect of the right forearm. A biopsy of the lesions was performed, confirming the diagnosis of angiosarcoma. The evaluation of tumor extension showed no distant metastasis. An amputation of the arm was performed. Angiosarcoma as a complication of primary lymphedema is a very rare entity with very poor prognosis.

Dermal melanocytic tumor with CRTC1‐TRIM11 fusion: Report of two additional cases with review of the literature of an emerging entity

"Cutaneous melanocytic tumor with CRTC1-TRIM11 fusion" (CMTCT) is a newly described, potentially novel entity that typically presents as a dermal nodule on the head and neck, extremities, and trunk of adults. Histopathologically, it is reported as a nodular or multinodular tumor composed of epithelioid and spindle cells that are variably immunoreactive for S100-protein, SOX10, and MITF along with more specific melanocytic markers such as MelanA and HMB45. With only 11 cases reported in the English literature so far, the neoplasm appears to behave in a relatively indolent fashion. Nevertheless, in one case, local recurrence and synchronous distant metastasis were evident after 13 years. Additional cases with longer follow-up are essential to determine the neoplasm's biologic behavior with more accuracy. Herein, two cases of CMTCT, one arising on the lower back of a 65-year-old female and the other on the arm of a 33-year-old female in addition to a comprehensive literature review are reported.

Converting primary tumor towards an in situ STING-activating vaccine via a biomimetic nanoplatform against recurrent and metastatic tumors

Currently, vaccine is a promising tumor prevention modality in cancer therapy. However, it is hard to elicit robust antitumor immunity in patients already afflicted with tumor, inspiring a need for a firenew and subversive cancer therapeutic vaccine. Herein, we reported an in situ STING (stimulator of interferon genes)-activating vaccination (ISSAV) strategy to completely convert primary tumor towards an in situ therapeutic STING vaccine for initiating highly effective and personalized antitumor immune responses. This ISSAV strategy represented a broad-spectrum cancer therapeutic vaccine, which break the shackles of heterogeneity and immunosuppression. We developed an ideational ingenious biomimetic nanoplatform (CMM-DiR) for achieving ISSAV strategy, which encapsulated STING-agonist (MnO2 NPs) and immobilized photothermal agent (DiR). In the tumor microenvironment (TME), CMM-DiR realized burst release of Mn2+, increased the pH value of TME, alleviated tumor hypoxia and induced the expose of numerous tumor-associated antigens from cancer cells. Accordingly, the primary tumor had the dual-function of as adequate antigens and STING agonist depots, thus transforming into a therapeutic STING vaccine. Importantly, the robust antitumor immunity of nanoplatform was observed in primary tumor, recurrent tumor, metastatic tumor and multinodular tumor, demonstrating that this ISSAV represents a technological advancement in the field of cancer vaccinations and personalized immunotherapy.

Un mycétome actinomycosique pseudotumoral de la fesse chez l’enfant : une observation

Mycetoma is a rare and neglected tropical disease among children. Extrapodal forms, in particular the buttock, are serious because they expose to visceral extension. We are reporting an observation remarkable for its clinical tumor presentation in a child. An 11-year-old boy was admitted at to the dermatology department for a buttock tumor that has been evolving for 2 years. Physical examination showed a multinodular, polyfistulized, and inflammatory tumor emitting red granules located in the buttocks. Mycological examination isolated Actinomadure pelletieri that confirms the diagnosis of actinomicotic mycetoma. The evolution, after a two-year follow-up, was positive under antibiotic therapy combining cotrimoxazol, clavulanic acid amoxicillin and streptomycin. Our observation is specific by the occurrence of a pseudotumoral actinomycotic buttock mycetoma in a child, the diagnostic delay and the favorable evolution without recurrence after a follow-up of 24-month.

Primitive Myxoid Mesenchymal Tumour of Nose.

Primitive Myxoid Mesenchymal Tumour of Infancy (P.M.M.T.I.) is a locally aggressive myofibroblastic tumour, occurring mostly in the first year of life. Grossly, it occurs as a non-encapsulated, multi-nodular tumour with focal infiltrative growth with a size ranging from 2 to 15cm. It is composed of primitive spindled cells in a myxoid background. It is a low-grade fibroblastic malignancy with low metastatic potential with a high local recurrence rate. On immunohistochemistry, it stains positive for Vimentin. no reactivity for smooth muscle actin, muscle specific actin, desmin, S-100 protein, or myogenin. Electron microscopy documented a poorly differentiated fibroblastic proliferation. The present case is of a P.M.M.T. occurring in the nose of a 3 ½ years old female child. This is the first case reported from Central India. The child had recurrent nasal growth and the excision biopsy was suggestive of intermediate grade fibroblastic neoplasm. The biopsy, on IHC staining, was positive for Vimentin and CD99 and negative for S-100, CD-34 and Desmin, favouring the diagnosis of P.M.M.T. The child had a total of three recurrence of growth after local excision before diagnosis was established. In the prior two surgeries, the histopathological analysis reported it as a benign nasal polyp. After the third surgery, the specimen was sent for IHC. Immunohistochemical stains helped in differentiating it from congenital infantile fibrosarcomas, a similar type of mesodermal tumour. The present case of Primitive myxoid mesenchymal tumour following IHC stains were positive for Vimentin, CD-99, CD-117 and NESTIN, pointing to the primitive nature of the tumour. It was negative for the neural marker. Since it is chemo resistant, the preferred method of treatment is wide surgical excision.

Large surgically resected leiomyosarcoma of the liver: a case report

BackgroundPrimary hepatic leiomyosarcoma (PHL) is an extremely rare type of tumor. We herein report a case of a large surgically resected leiomyosarcoma of the liver.Case presentationA 69-year-old man with a feeling of epigastric compression was referred for examination of an abdominal mass. He had no history of liver disease or alcohol abuse. Liver function tests indicated Child-Pugh class A. Tumor markers were negative. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a relatively well-contrasted 12 × 11 × 8 cm tumor with well-defined boundary replacing the lateral segment of the liver alongside multiple intrahepatic metastases. Several nodules up to 12 mm were found in both lungs, suggestive of metastasis. SUVmax of the liver mass and lung tumor in positron emission tomography were 10.4 and 1.5, respectively. Hepatocellular carcinoma was primarily suspected. Lateral segmentectomy of the liver was performed to confirm diagnosis and prevent tumor rupture. Macroscopically, the lateral segment of the liver had been replaced by a lobular or multinodular tumor with a maximum diameter of 15 cm. In pathological findings, the tumor consisted of bundle-like proliferation of complicated banding spindle-like cells with clear cytoplasm, accompanied by storiform pattern and compressed blood vessels. Nuclear fission images were observed in 8/10 HPF. Partial necrosis was present, with associated venous invasion and intrahepatic metastasis. Immunohistochemical staining for tumor cells revealed desmin, α-smooth muscle actin (αSMA), and h-caldesmon were all positive, informing a final diagnosis of PHL. The postoperative course was uneventful, and he was discharged on the 12th postoperative day.ConclusionsPHL is a rare malignant disease with relatively poor prognosis. To confirm a diagnosis of PHL, immunohistochemical analysis as well as histopathological findings is important. The preferred treatment is surgical resection, sometimes in combination with adjuvant chemotherapy and radiotherapy. Further studies are needed to elucidate and better understand this uncommon clinical entity.

SUN-931 Characterization of an Ovarian Steroid Cell Tumor in a VHL Patient

Most ovarian steroid cell tumors arise sporadically. However, they can also be observed as a rare manifestation of von Hippel Lindau disease. Here, we present a clinical, pathological and molecular characterization of a steroid cell tumor in a VHL patient. A 14 year old girl with molecularly confirmed diagnosis of VHL developed hirsutism and amenorrhea. Initial clinical hormonal evaluation was notable for elevated 17-OHP of 406ng/dl, androstenedione 275ng/dl, and testosterone 102ng/dl. In order to exclude congenital adrenal hyperplasia as a common cause of hirsutism in adolescents, ACTH stimulation was performed, but no increase in 17-OHP was observed. Anti Muellerian hormone, inhibin (INH) A and INH B were normal. Imaging revealed a bilobed 6cm left adnexal mass. The mass was resected en bloc via a left oophorectomy. Pathological evaluation showed multinodular steroid cell tumor with clear cytoplasm and delicate vascular meshwork. Immunoprofiling demonstrated positivity for inhibin and calretinin; while renal cell carcinoma markers were negative. All laboratory values normalized post-surgery. In addition to clinical measurements pre- and post-surgery, steroid profiles were evaluated by LC-MS/MS. Quantitative RT-PCR analysis showed robust tumor expression of enzymes facilitating the production of androgens, but not estrogens. Further preliminary analysis by exome sequencing confirmed the known germline pathogenic variant in VHL, but no additional obvious somatic driver mutations were identified. Interestingly, the NGS analysis of different specimens from the same tumor revealed multiple different single base pair variants in the VHL gene as a second hit. In summary, hirsutism in VHL patients should raise the suspicion for unusual ovarian tumors. In contrary to the usual theory of a monoclonal expansion after loss of the wt VHL allele, this tumor appeared to be oligoclonal as evidenced by different somatic VHL mutations. This could be either explained by initial parallel occurrence of several clones or that the VHL second hit is not an initial event, but the mutation instead supports tumor expansion following initial steps of tumorigenesis.