Pulmonary Chondroma Research Articles

Gastrointestinal stromal tumor in Carney’s triad with laparoscopic total gastrectomy: a case report

IntroductionCarney's triad is a rare syndrome characterized by the co-occurrence of gastric gastrointestinal stromal tumor (GIST), pulmonary chondroma, and extra-adrenal paraganglioma. We present a case of a young woman with GISTs associated with this triad.Case presentationA 28-year-old woman was identified with multiple gastric tumors and a right lung nodule during a routine health check-up. CT scans and upper gastrointestinal endoscopy revealed a 50 mm mass on the lesser curvature of the stomach, along with two additional gastric lesions and a 20 mm nodule in the right lung. The patient had a history of right middle lobectomy at the age of 19 for pulmonary chondroma. During surgery, enlarged lymph nodes were observed, indicating metastasis, which necessitated a total gastrectomy with radical (D2) lymph node dissection. Pathological examination confirmed seven GISTs, with immunohistochemical staining positive for KIT (+), DOG1 (+), and negative for SDHB (−). The postoperative course was uneventful, and the patient was discharged on the seventh postoperative day. Despite opting out of adjuvant imatinib therapy, she remains disease-free 2 years postoperatively.ConclusionsThis case underscores the necessity of total gastrectomy with lymph node dissection due to the high incidence of metastasis in GISTs associated with Carney's triad. Further research is required to determine the optimal extent of lymph node dissection in such cases.

Histopathological spectrum of lung findings in autopsy cases

Background: The incidence of lung pathology is the most common autopsy finding and is responsible for a great deal of mortality and morbidity. It is affected by a wide variety of respiratory pathogens and is involved in many systemic diseases. It is secondarily involved in almost all forms of terminal disease. Radiological findings are usually nonspecific in lung diseases and need prompt histopathological examination to find out the exact cause of death. Aims and Objectives: The aim is to study the spectrum of histopathological findings in lung in autopsy cases. Materials and Methods: This is a retrospective study done in the Department of Pathology at Government Kilpauk Medical College and Hospital during the year 2022. Lung specimens were received from the Forensic medicine department. Gross findings were noted. Following adequate formalin fixation, the tissue specimens were processed and paraffin sectioning was done followed by hematoxylin and eosin staining. The findings were documented and the results were analyzed. Results: Among 100 cases studied during year maximum cases were seen in the age group of 31–40 years (32%). Males (72%) were more commonly affected than females (28%). The most common findings are Pulmonary edema (34%) followed by congestion (32%) and other findings include emphysematous change (13%), pneumonia (10%), tuberculosis (6%), metastatic adenocarcinomatous deposits (1%), primary well-differentiated adenocarcinoma (1%), pulmonary chondroma (1%), and bronchiectasis (1%). Conclusion: The most common finding observed was pulmonary edema. In our study, male preponderance was noted. This study emphasizes to scrutinize the histopathological findings in the lung, especially following a sudden death.

The Carney Triad

Abstract Introduction/Objective Carney triad is a multi-tumor syndrome comprising of gastrointestinal stromal tumor (GIST), extra-adrenal paraganglioma and pulmonary chondroma that was first described in 1977. The purpose of this report of this to remind the pathologists about this triad and about the fact that pathology is far beyond just giving a diagnosis on a surgical specimen. Methods/Case Report A 41-year-old female presented with dizziness, nausea, vomiting, weakness, early satiety, and palpitations. She was found to be pregnant, and an ultrasound showed an intrauterine pregnancy along with a large abdominal mass. A subsequent computed tomography (CT) scan demonstrated a left adrenal heterogeneous mass. CT chest was also performed which demonstrated a 0.3 cm right middle lobe pulmonary nodule, compatible with a benign tumor. Lab work showed cortisol, dehydroepiandrosterone sulfate (DHEAS), and adrenocorticotropic hormone (ACTH) to be within normal limits, but both metanephrine and normetanephrine were elevated. The patient was treated with an alpha and beta blockade prior to undergoing an adrenalectomy. During adrenalectomy an incidental mass was found at the greater curvature of the stomach. On gross examination, the adrenal mass was a large, encapsulated, brown-black, multi-lobulated, weighing 1,427 grams and measuring 19.8 x 13.7 x 11.6 cm. Microscopically, the mass was consistent with an extra-adrenal paraganglioma, compressing the adjacent normal adrenal gland and not invading or arising from it. The stomach mass was grossly tan-yellow, multi-lobulated, and firm. The cut sections were variegated tan, white. Microscopically, the mass was consistent with a GIST. Results (if a Case Study enter NA) NA Conclusion Individual diagnoses were rendered for the adrenalectomy and gastric mass specimens. Additionally, possibility of carney’s triad was suggested based on patient’s chest imaging findings.

Thorahcic SMARCA4-deficient undifferentiated tumors with ganglioneuroma and enchondroma: implications for SLC7A11 and ARID1A expression: a case report

BackgroundSWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4-deficient thoracic sarcoma (SMARCA4-DTS) is a rare disease that has recently been described as an entity. It is characterized by an aggressive clinical course and specific genetic alterations. As an immunohistological feature, the tumors are deficient in SMARCA4 and SMARCA2 and express sex-determining region Y (SRY)-box 2 (SOX2). Occasionally, there are cases that are less frequent and difficult to distinguish from SMARCA4-deficient non-small cell lung carcinoma (SMARCA4-dNSCLC). Therefore, the 5th edition of the World Health Organization (WHO) classification describes thoracic SMARCA 4-deficient undifferentiated tumors (SMARCA4-UT). In contrast, Carney’s triad is a syndrome that combines three rare soft tissue tumors: gastric leiomyosarcoma, pulmonary chondroma, and extra-adrenal paraganglioma. Protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A) has been proposed as the causative gene. Both diseases are valuable cases; moreover, there have been no previous reports of their coexistence.Case presentationA 43-year-old man visited our hospital because of respiratory distress. Computed tomography revealed a large mass measuring 55 mm in the upper lobe of the right lung and front mediastinum, with metastases in the surrounding lymph nodes. Needle biopsy was performed for diagnosis, and histological examination of the samples revealed monotonous epithelioid-like cells with loose binding and sheet-form proliferation. The tumor cells had distinct nuclei with some rhabdoid-like cells. Immunohistochemical analysis revealed that the tumor cells were positive for AE1AE3, SOX2, CD34, and p53 and negative for SMARCA4 and SMARCA2. The patient died 6 months after admission, without any treatment. Autopsy revealed ganglioneuroma and enchondroma suggestive of an incomplete Carney complex.ConclusionSMARCA4-UT is a rare and recently established disease. While it is difficult to diagnose, it is necessary to distinguish undifferentiated carcinoma, large cell carcinoma, Ewing sarcoma, and epithelioid sarcoma when diagnosing tumors involving the mediastinum. Moreover, cases of SMARCA4-UT with ganglioneuroma and enchondroma are very rare. We discuss and report a case of SMARCA4-UT in which we also examined ARID1A and SLC7A11expression.

Carney\u2019s triad in an adult male from a tertiary care center in India: a case report

BackgroundCarney’s triad is a rare syndrome comprising gastrointestinal stromal tumor, extra-adrenal paraganglioma, and pulmonary chondroma along with newer additions of adrenal adenoma and esophageal leiomyoma. The triad is completely manifest in only 25–30% cases, with most patients presenting with two out of three parts of the syndrome. Wild-type succinate-dehydrogenase-deficient gastric gastrointestinal stromal tumor forms the most common component of Carney’s triad and is usually multicentric and multifocal. It usually demonstrates indolent behavior and resistance to imatinib; hence, the management remains predominantly surgical. Pulmonary chondromas are commonly unilateral and multiple with slow-growing nature, which allows for conservative management. Adrenocortical adenomas are found in 20% of patients and are usually detected as incidentalomas.Case presentationA 49-year-old Asian male presented with upper gastrointestinal bleed and was diagnosed with multiple gastric succinate-dehydrogenase-deficient gastrointestinal stromal tumors. On evaluation, he was found to have left pulmonary chondroma and non-secretory adrenal adenoma, thus completing the Carney’s triad. He underwent surgery with sleeve gastrectomy and excision of the antral tumor nodule, while the adrenal and pulmonary tumors have been under close follow-up.ConclusionLiterature regarding Carney’s triad is scarce, especially from the Indian setting. Our report aims to highlight the various manifestations of this syndrome with emphasis on management of wild-type succinate-dehydrogenase-deficient gastrointestinal stromal tumor. Radical gastric surgeries do not offer a survival advantage in this condition; hence, more conservative modalities of resection can be adopted.

S3189 Not Just a GIST: A Rare Case of Gastric Leiomyosarcoma

Introduction: Leiomyosarcoma (LMS) is a malignant neoplasm showing smooth muscle differentiation. Before the recognition of gastrointestinal stromal tumors (GISTs), leiomyoarcomas were commonly reported in the gastrointestinal tract due to misclassification. Now, these tumors are considered rare with only 16 cases of gastric LMS reported in the post-GIST era. We present the 17th case of primary gastric LMS. Case Description/Methods: An 81F with a history of GERD,CHF and Afib presented for evaluation of syncope. She had also suffered with increased fatigue, poor appetite, 30lb unintentional weight loss, and a “gnawing” post-prandial epigastric pain. Her last EGD was 4 years prior which showed non bleeding erosive gastropathy and a non obstructing Schatzki’s ring. Biopsies showed chronic gastritis without evidence of dysplasia or H. Pylori. On admission, pertinent labs included Hg of 11.5 g/dL, MCV 99.7 fL, WBC 11.02 k/uL, and albumin 2.8 g/dL. She underwent an EGD which showed a large, infiltrative, transmural, ulcerated, non-circumferential mass in the greater curvature of the stomach. EUS showed a hypoechoic lesion which appeared to extend to the cardia by extrinsic involvement of the gastric wall. Biopsies showed an ulcerated spindle cell neoplasm which stained negative for C-kit and DOG1, but were strongly positive for desmin. This conformed the diagnosis of gastric leiomyosarcoma. Discussion: Before the development of immunohistochemical staining for C-kit, many GISTs were misdiagnosed as LMSs and leiomyoblastomas. Now these tumors are considered rare with only 16 prior case reports. The diagnosis mainly relies on pathologic examination with SMA, desmin, and h-caldesmon are positive in the majority ( >70%) of LMSs. CD117 (KIT), DOG 1 and CD34 are negative. It is important to rule out Carney tried, which is a type of multiple endocrine neoplasia which encompasses LMSs, pulmonary chondroma, and extra-adrenal paragangliomas. Complete for LMS surgical resection with negative margins remains the gold standard of treatment. It is important to note that not every spindled lesion is a GIST, as diagnosis will change management. As opposed to GISTs, LMSs are not likely to respond to Imatinib. Due to concern for splenic invasion, neoadjuvant chemotherapy was pursued in our patient with Ifosfamide and doxorubicin prior to surgical resection. Due to her other comorbidities, she was felt to be too high risk for surgery and she eventually chose to pursue hospice.Figure 1.: Figure 1 1a: Ulcer in the incisura of the stomach 1b: Ulcer status post hemostatic clip and argon plasma coagulation (APC).

A Case of Carney Triad Complicated by Renal Cell Carcinoma and a Germline SDHA Pathogenic Variant

Background: Carney triad is a rare multiple-neoplasia syndrome presenting as an association of paragangliomas (PGL), gastrointestinal stromal tumors (GIST), and pulmonary chondromas (CHO). Succinate dehydrogenase deficiency has been associated with several neoplasias, including Carney triad, renal cell carcinoma (RCC) and those associated with hereditary PGL/ pheochromocytoma (PHEO) syndromes. Clinical Case: A 57-year-old male diagnosed with hypertension at age 49, presented with a gradual increase in blood pressure over a period of 12 months. For seven years following his diagnosis of hypertension, the patient experienced episodic increases in blood pressure, to a systolic pressure greater than 180 mmHg associated with a tight band sensation around his forehead lasting half a day. Abdominal computed tomography (CT) revealed a left adrenal adenoma, a 5.1 cm para-aortic mass, and a right renal superior pole lesion measuring 2.5 cm, which was suspicious for a carcinoma. 123I-metaiodobenzylguanidine (123I-MIBG) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) scans were performed, which suggested the para-aortic mass to be consistent with a PGL. Additionally, 18F-FDG uptake was noted in the gastroesophageal region and was suspicious for a GIST. The left adrenal mass was not associated with 123I-MIBG or 18F-FDG activity. Chest CT demonstrated a right middle lobe lung lesion suggestive of a CHO, although no biopsy was performed. A diagnosis of Carney triad was made. The patient underwent surgical resection of the PGL and GIST, as well as a partial right nephrectomy. The PGL and GIST were positive for SDHA and negative for SDHB by immunohistochemical (IHC) staining. Pathology from the renal lesion was consistent with a 2.3 cm conventional clear cell renal carcinoma, with positive staining for SDHA and SDHB by IHC. The patient was found to harbor a germline heterozygous pathogenic variant (c.91 C>T, p.R31X) in SDHA which has been previously reported and results in loss of function of SDHA. SHDC hypermethylation was not detected in the PGL, GIST, or RCC. Additionally, DNA sequencing of the RCC did not indicate loss of heterozygosity at the variant region of interest. Although the SDHA disease-causing variant is responsible for the patients Carney triad phenotype, it is unclear if this variant is causative of the RCC. Conclusion: This is a novel presentation of a germline inactivating SDHA pathogenic variant in a patient with Carney triad complicated by RCC. However, an SDHA disease-causing variant was previously reported in a patient with comorbid GIST and RCC. This case provides further support to the increasing evidence that SDHx pathogenic variants may predispose patients to develop renal neoplasms.

Carney Triad, Carney-Stratakis Syndrome, 3PAS and Other Tumors Due to SDH Deficiency.

Succinate dehydrogenase (SDH) is a key respiratory enzyme that links Krebs cycle and electron transport chain and is comprised of four subunits SDHA, SDHB, SDHC and SDHD. All SDH-deficient tumors are caused by or secondary to loss of SDH activity. As many as half of the familial cases of paragangliomas (PGLs) and pheochromocytomas (PHEOs) are due to mutations of the SDHx subunits. Gastrointestinal stromal tumors (GISTs) associated with SDH deficiency are negative for KIT/PDGFRA mutations and present with distinctive clinical features such as early onset (usually childhood or adolescence) and almost exclusively gastric location. SDH-deficient GISTs may be part of distinct clinical syndromes, Carney-Stratakis syndrome (CSS) or dyad and Carney triad (CT). CSS is also known as the dyad of GIST and PGL; it affects both genders equally and is inherited in an autosomal dominant manner with incomplete penetrance. CT is a very rare disease; PGL, GIST and pulmonary chondromas constitute CT which shows female predilection and may be a mosaic disorder. Even though there is some overlap between CT and CSS, as both are due to SDH deficiency, CSS is caused by inactivating germline mutations in genes encoding for the SDH subunits, while CT is mostly caused by a specific pattern of methylation of the SDHC gene and may be due to germline mosaicism of the responsible genetic defect.

A case of Carney triad complicated by renal cell carcinoma and a germline SDHA pathogenic variant.

SummarySuccinate dehydrogenase deficiency has been associated with several neoplasias, including renal cell carcinoma (RCC) and those associated with hereditary paraganglioma (PGL)/ pheochromocytoma (PHEO) syndromes, Carney dyad, and Carney triad. Carney triad is a rare multitumoral syndrome characterized by co-existing PGL, gastrointestinal stromal tumor (GIST), and pulmonary chondroma (CHO). We report a case of a 57-year-old male who presented with para-aortic and gastroesophogeal masses, and a right renal superior pole lesion, which were classified as multiple PGLs, a GIST, and a clear cell renal carcinoma, respectively, on pathology following surgical resection. Additionally, a CHO was diagnosed radiologically, although no biopsy was performed. A diagnosis of Carney triad was made. SDHB immunohistochemical staining was negative for the PGL and the GIST, indicating SDH-deficiency. Interestingly, the renal cell carcinoma (RCC) stained positive for both SDHB and SDHA. Subsequent genetic screening of SDH subunit genes revealed a germline inactivating heterozygous SDHA pathogenic variant (c.91 C>T, p.R31X). Loss of heterozygosity was not detected at the tumor level for the RCC, which likely indicated the SDHA variant would not be causative of the RCC, but could still predispose to the development of neoplasias. To the knowledge of the authors this is the first reported case of an SDHA pathogenic variant in a patient with Carney triad complicated by RCC.Learning points The succinate dehydrogenase enzyme is encoded by four subunit genes (SDHA, SDHB, SDHC, and SDHD; collectively referred to as SDHx), which have been implicated in several neoplasias and are classified as tumor suppressor genes. Carney triad is a rare multiple-neoplasia syndrome presenting as an association of PGLs, GISTs, and CHOs. Carney triad is most commonly associated with hypermethylation of SDHC as demonstrated in tumor tissue, but approximately 10% of cases are due to pathogenic SDHx variants. Although SDHB pathogenic variants are most commonly reported in SDH-deficient renal cell carcinoma, SDHA disease-causing variants have been reported in rare cases.

SDHC Methylation Pattern in Patients With Carney Triad.

Carney triad is a multitumor syndrome affecting almost exclusively young women in a nonfamilial setting, which manifests by multifocal gastric gastrointestinal stromal tumors, paragangliomas, and pulmonary chondroma. The Carney triad-associated tumors are characterized by a deficiency of the mitochondrial succinate dehydrogenase enzymatic complex. Recently, it has been observed that the deficiency results from epigenetic silencing of the SDHC gene by its promoter hypermethylation. To elucidate anatomic distribution of SDHC promoter methylation in Carney triad patients and thus to shed some light on the possible natural development of this epigenetic change, both neoplastic and available non-neoplastic tissues of 3 patients with Carney triad were tested for hypermethylation at the SDHC promoter site. SDHC promoter hypermethylation was proven in all tumors studied. Lack of SDHC epigenetic silencing in the non-neoplastic lymphoid and duodenal tissue (ie, tissues not involved in the development of Carney triad-associated tumors) together with the finding of SDHC promoter hypermethylation in the non-neoplastic gastric wall favors the hypothesis of postzygotic somatic mosaicism as the biological background of Carney triad; it also offers an explanation of the multifocality of gastrointestinal stromal tumors of the stomach occurring in this scenario as well. However, the precise mechanism responsible for the peculiar organ-specific distribution of Carney triad-associated tumors is still unknown.

GIANT PULMONARY CHONDROMAS AS A COMPONENT OF CARNEY’S TRIAD

Carney’s triad is a rare syndrome, comprising of the GIST of the stomach, functioning extra-adrenal paraganglioma and pulmonary chondroma. We present a case of a young woman diagnosed with gastric GIST, mesenteric paraganglioma and two giant chondromas of the left lung. Due to the rapid growth of pulmonary neoplasms and their potential malignant behaviour, the left pneumonectomy was performed.

From This Month's Histopathology

Despite good evidence that screening for Lynch Syndrome (LS) in endometrial carcinoma (EC) cases has high potential for reducing morbidity, mortality, and healthcare costs, and the wide availability of screening tests, there remains huge variation in the approach to screening. Pathologists need to be aware of the implications of LS screening for the patient and her family. Standardised and external quality-assured protocols should be developed and adopted for LS screening in EC cases. The International Society of Gynaecological pathology (ISGyP) has recently recommended that all newly diagnosed EC cases undergo testing for LS…We also suggest that all newly diagnosed patients with ovarian endometrioid or clear cell carcinoma are similarly screened for LS. MSH2 loss in a case of known germline MSH2 mutation. study Ryan et al. (p. 814) In conclusion, SDHB immunohistochemistry can be a useful tool for the differential diagnosis of pulmonary chondromas and hamartomas, in cases when this distinction is difficult based on histological features alone. Loss of SDHB expression in pulmonary chondromas may also assist in the identification of patients who may have Carney triad and are therefore at risk of developing more aggressive neoplasms. Succinate dehydrogenase B (SDHB) immunohistochemical staining in a case of chondroma. Cartilaginous cells (left) are not reactive. Endothelial cells (right) show granular cytoplasmic reactivity: SDHB expression is lost. Chatzopoulos et al. (p. 826) In summary, we have shown that a Ki67 PI of ≥25 was associated with poorer survival in high-grade Olfactory Neuroblastomas (ONBs), and that high-grade ONBs show more intratumoral Tumour Infiltrating Lymphocytes (TILs) than low-grade ONBs…and the CD4/CD8 ratio could also represent an interesting prognostic marker. This series confirms the importance of histological grading, and that a careful evaluation of TILs could prove to be a powerful prognostic tool for identifying patients with distinct clinical behaviours and responses to immunotherapeutic strategies. Ki67 proliferation index (PI) in a Hyams Grade I olfactory neuroblastoma. Classe et al. (p. 854) In summary, this study investigated the largest cohort, to our knowledge, of Nested Variant urothelial Carcinoma (UVUC) to date and aimed to identify the mutational and molecular backgroundsof this rare UC variant. NVUC seems to be characterised by a high frequency of TERT mutations and low frequency of mutations in FGFR3 and the mTOR, MAPK and PIK3 pathways. Mutations of Wnt and inflammatory pathways, including JAK3 mutations, may indicate a differential mutational landscape of this specific histomorphological variant compared to conventional UBC. Moreover, we were able to assign NVUC to the luminal subtype of UC. Our findings may be of significance in understanding the pathogenesis of this rare variant and may guide further diagnostic, prognostic and therapeutic applications. Heatmap presenting immunohistochemistry results for luminal and basal markers in NVUC. Weyerer et al. (p. 866) In conclusion, the analysis of stromal maturity in gastric cancer is feasible with moderate reproducibility, and stromal maturity is an independent prognostic factor in gastric adenocarcinoma… classification of stromal response in this tumour type would benefit from more detailed criteria, preferably based on those biological mechanisms of the response mediating the prognostic effect.. Studies in neoadjuvant-treated patients and early-stage gastric cancer are warranted. 5-year overall survival of patients with intestinal-type gastric adenocarcinoma. Kemi et al. (p. 883) We have shown that Vacuum-assisted large-core biopsy (VALCB) is reliable for excluding malignancy, and allows the avoidance of surgical excision when there is no discordance between radiological and histological findings, and no associated atypia on biopsy. When a VALCB contains atypia, additional risk factors are the non-incidental finding of the RS/CSL, the mammographic appearance, and the number of fragments sampled being <12. When they are present, surgery remains safer. Example of a benign biopsy with a pure radial scar/complex sclerosing lesion. Bacci et al. (p. 901)

18F-FDG PET/CT “hepatic superscan” in incomplete Carney’s triad

Introduction. Carney triad is a rare non-hereditary condition characterized by gastrointestinal stromal tumors ? intramural mesenchymal tumors of the gastrointestinal tract with neuronal or neural crest cell origin, pulmonary chondromas, and extra-adrenal paragangliomas. The term incomplete Carney triad more precisely refers to the occurrence of at least two of these tumor types. Carney triad named after J. Aidan Carney is considered to be a specific type of multiple endocrine neoplasia. Less than 30 cases of complete and less than 100 cases of incomplete Carney triad have been reported worldwide. Carney triad primarily affects young women (mean age of onset of 20 years). Case outline. A 35-year-old female patient had an initial presentation at the National PET Center, Clinical Center of Serbia, after the gastrectomy, with multiple hepatic metastases as well as bilateral pulmonary chondromas. 18F-FDG PET/CT scan revealed the following: 1) intense 18F-FDG uptake in the liver metastatic lesions, with reduced physiological activity in the brain and heart, bowel, and renal tracer uptakes commonly known as FDG hepatic superscan; 2) multiple irregular-shaped lesions, mostly calcified in bilateral pulmonary parenchyma; 3) a nodular lesion in the left adrenal gland with accumulation of 18F-FDG in its anterior part. Conclusion. The present study describes a hepatic superscan in a patient with incomplete Carney triad, including gastrointestinal stromal tumors and pulmonary bilateral chondromas, as well as a tumor in the left adrenal gland.

Loss of succinate dehydrogenase B immunohistochemical expression distinguishes pulmonary chondromas from hamartomas.

Pulmonary chondromas, which are rare cartilaginous neoplasms that often arise in the setting of Carney triad, are morphologically similar to pulmonary hamartomas, which are much more common. There is evidence that succinate dehydrogenase (SDH) deficiency drives neoplasia in patients with Carney triad, and SDHB immunohistochemistry can be used as a surrogate markerto detect SDH deficiency. The aim of this study was to investigate the utility of SDHB immunohistochemistry in distinguishing pulmonary chondromas from hamartomas. Immunohistochemistry for SDHB (clone 21A11AE7) was performed on histological sections from six cases of pulmonary chondroma and 33 cases of pulmonary hamartoma. SDHB expression was retained in all 33 pulmonary hamartomas, and lost in the majority of evaluable chondromas (five of six). Of the five patients with chondromas showing SDHB loss, four had definitiveCarney triad. Most patients with pulmonary hamartomas were older males with small solitary masses, whereas chondromas often presented as multiple masses in young females. Loss of SDHB immunohistochemical expression can be useful for differentiating pulmonary chondromas from hamartomas, and potentially identifying patients with Carney triad.

Paragangliomas in Carney-Stratakis Syndrome.

Carney-Stratakis Syndrome (CSS) comprises of paragangliomas (PGLs) and gastrointestinal stromal tumors (GISTs). Several of its features overlap with Carney Triad (CT) - PGLs, GISTs, and pulmonary chondromas. CSS has autosomal dominant inheritance, incomplete penetrance, and greater relative frequency of PGL over GISTs. The PGLs in CSS are multicentric and GISTs are multifocal in all the patients, suggesting an inherited susceptibility and associating the two manifestations. In this review, we highlight the clinical, pathological, and molecular characteristics of CSS, along with its diagnostic and therapeutic implications.

Computed Tomography Imaging Findings of Pulmonary Chondroma

Purpose To characterize the computed tomography (CT) imaging findings in patients with pulmonary chondroma. Methods We examined CT imaging findings of eight patients with histopathologically verified pulmonary chondroma. We assessed the location, size, shape, margins, amount of calcification, calcification pattern, and attenuation on precontrast and enhancement CT. Results All patients exhibited solitary, mildly lobulated pulmonary masses, which were located in the right lung in four cases and the left lung in four cases. The mean lesion size was 3.7 cm (range 0.9–10.7 cm). All eight tumours had a well-defined margin. On plain CT images, seven of the cases (87.5%) showed a mass with varying degrees of calcification, which included strip-like punctate (n=5) and ring (n=2) patterns. One patient with a large lesion (10.7 cm) showed chest wall adhesion. On contrast-enhanced CT images, all lesions demonstrated slight inhomogeneous enhancement ≤14 HU. Conclusion CT is the reference standard diagnostic technique for locating pulmonary chondroma. In most cases, CT findings show some characteristics that are important in the diagnosis, surgical planning, and follow-up of the tumour.

Expression of succinate dehydrogenase subunit protein in succinate dehydrogenase-deficient gastrointestinal stromal tumors

Objective: To investigate the expression of succinate dehydrogenase complex subunit protein in succinate dehydrogenase-deficient gastrointestinal stromal tumors (SDH-deficient GISTs). Methods: Three hundred fifty-two cases of GISTs were collected from January 2003 to January 2017 at the Affiliated Hospital of Guizhou Medical University and West China Hospital of Sichuan University.The expression of succinate dehydrogenase subunit protein was detected by immunohistochemical EnVision technique in 352 cases of GISTs, and the negative cases were analyzed for clinicopathologic features and outcome. The gene segments of CKIT exons 9, 11, 13 and 17 and PDGFRA exons 12 and 18 were amplified and detected in SDH-deficient (negative) cases. Results: A total of 15 SDHB-deficient (negative) GISTs (4.3%, 15/352) were found among 352 cases of GISTs. Six patients were male and nine were female. The age of initial diagnosis ranged from 15 to 84 years (median=53 years, mean=47 years). The tumor involved stomach (14 cases) and mesentery (1 case). The tumor sizes varied from 0.5 cm to 15.0 cm (mean=6.9 cm). There were six, six and three cases of epithelioid, mixed and spindle cell types respectively. Eight cases showed multi-nodularity in the wall of stomach. Metastasis to lymph node was noted in four cases, one case showed intraperitoneal implantation metastasis. Metastases to liver, pancreas and lymph node were found in one case, and one case showed vascular invasion. Among SDHB-deficient GISTs, two SDHA-deficient (negative) cases were found (0.6%, 2/352), but there were no SDHC and SDHD deficient (negative) cases. Five of the fifteen SDH-deficient GISTs had follow-up data: one patient died 8 months after surgery from unknown cause, four had no recurrences or metastases, and there was no history of paraganglioma and pulmonary chondroma found in patients and their families. No mutation in CKIT and PDGFRA gene was identified in 15 cases of SDH-deficient GISTs. Conclusion: SDH-deficient GISTs have unique clinicopathologic features and a favorable prognosis, and a small proportion of cases are SDHA-deficient.

Succinate dehydrogenase (SDH)-deficient neoplasia.

The succinate dehydrogenase (SDH) complex is a key respiratory enzyme composed of four subunits: SDHA, SDHB, SDHC and SDHD. Remarkably, immunohistochemistry for SDHB becomes negative whenever there is bi-alleic inactivation of any component of SDH, which is very rare in the absence of syndromic disease. Therefore, loss of SDHB immunohistochemistry serves as a marker of syndromic disease, usually germline mutation of one of the SDH subunits. Tumours which show loss of SDHB expression are termed succinate dehydrogenase-deficient. In addition to loss of SDHB, tumours associated with SDHA mutation also show loss of SDHA expression. Fifteen per cent of pheochromocytoma and paraganglioma (PHEO/PGL) are associated with germline SDH mutation, and therefore SDH-deficient. We recommend screening SDHB immunohistochemistry for all PHEO/PGL. SDH-deficient gastrointestinal stromal tumours (GISTs) show distinctive features, including absent KIT proto-oncogene receptor tyrosine kinase/platelet-derived growth factor receptor A (KIT/PDGFRA) mutations [but positive staining for cKIT and DOG1], virtually exclusive gastric location, lobulated growth, multi-focality, a prognosis not predicted by size and mitotic rate, frequent metastasis to lymph nodes and primary resistance to imatinib therapy. Thirty per cent are associated with SDHA germline mutation and 50% are associated with SDHC epimutation (post-zygotic promoter hypermethylation) - the hallmark of the syndromic but non-hereditary Carney triad (SDH- deficient GIST, SDH-deficient paraganglioma and pulmonary chondroma). SDH-deficient renal carcinoma is newly recognized under the World Health Organization (WHO) 2016 classification and shows vacuolated eosinophilic cytoplasmic and cytoplasmic inclusions. It is particularly associated with SDHB mutation, although SDHC and SDHA mutation occur. SDH-deficient pituitary adenomas are recognized, but appear to be the least common SDH-deficient neoplasm.

68Ga-DOTA-TATE PET/CT for Molecular Imaging of Somatostatin Receptor Expression in Extra-adrenal Paraganglioma in a Case of Complete Carney Triad

Carney triad is a very rare syndrome characterized by the synchronous or metachronous occurrence of gastrointestinal stromal tumors, pulmonary chondroma, and extra-adrenal paraganglioma. We present the case of a 36-year-old woman with complete Carney triad who underwent a Ga-DOTA-TATE PET/CT scan for restaging of metastasizing extra-adrenal paraganglioma and for evaluation of targeted radionuclide therapy potential. On the Ga-DOTA-TATE PET scan, increased tracer accumulation was observed in paraganglioma metastases. This case highlights the usefulness of Ga-DOTA-TATE PET/CT for restaging of metastasizing paraganglioma in Carney triad and the option of targeted radionuclide therapy in this entity.

Succinate dehydrogenase (SDH) deficiency, Carney triad and the epigenome.

In this report, we review the relationship between succinate dehydrogenase (SDH) deficiency and the epigenome, especially with regards to two clinical conditions. Carney triad (CT) is a very rare disease with synchronous or metachronous occurrence of at least three different tumor entities; gastric gastrointestinal stromal tumor (GIST), paraganglioma (PGL), and pulmonary chondroma. This condition affects mostly females and it is never inherited. Another disease that shares two of the tumor components of CT, namely GIST and PGL is the Carney-Stratakis syndrome (CSS) or dyad. CSS affects both genders during childhood and adolescence. We review herein the main clinical features and molecular mechanisms behind those two syndromes that share quite a bit of similarities, but one is non-hereditary (CT) whereas the other shows an autosomal-dominant, with incomplete penetrance, inheritance pattern (CSS). Both CT and CSS are caused by the deficiency of the succinate dehydrogenase (SDH) enzyme. The key difference between the two syndromes is the molecular mechanism that causes the SDH deficiency. Most cases of CT show down-regulation of SDH through site-specific hyper-methylation of the SDHC gene, whereas CSS cases carry inactivating germline mutations within one of the genes coding for the SDH subunits A, B, C, or D (SDHA, SDHB, SDHC, and SDHD). There is only partial overlap between the two conditions (there are a few patients with CT that have SDH subunit mutations) but both lead to increased methylation of the entire genome in the tumors associated with them. Other tumors (outside CT and CSS) that have SDH deficiency are associated with increased methylation of the entire genome, but only in CT there is site-specific methylation of the SDHC gene. These findings have implications for diagnostics and the treatment of patients with these, often metastatic tumors.