Extraovarian granulosa cell tumor (GCT) is a very uncommon tumor, assumed to arise from the ectopic gonadal tissue along the embryonal route of the genital ridge. A 54 years old female patient presented with a mass and acute pain in abdomen. Exploratory laparatomy revealed hemoperitoneum with a large mesenteric mass measuring 13 × 12 cm in size, showing extensive areas of haemorrhages. Histopathological examination of the excised mass showed features of adult-type GCT. As the patient had a history of hysterectomy with bilateral salpingo-oophorectomy 10 years ago for ‘‘leiomyoma” with no evidence of GCT of the ovary in the histopathology report, a diagnosis of extraovarian GCT was made. A diagnosis of extraovarian GCT should be carried out after excluding any previous history of GCT of the ovary. Tumor rupture with haemoperitoneum is a well-known complication of GCT. Extraovarian GCT is a rare tumor with only 10 cases reported in literature. The case is presented for its rarity.
Granulosa cell tumors (GCTs) of the ovary belong to the group of ovarian sex-cord stromal tumors and represent 5 to 10% of ovarian malignancies. GCTs exhibit several morphological, biochemical and hormonal features of normal proliferating pre-ovulatory granulosa cells, such as estrogen biosynthesis. Prognostic factors of this condition are lacking, and alternative treatment options to preserve future fertility are needed. Several groups have shown that two genetic factors implicated in GCTs are of particular interest. The gsp oncogene is a constitutive activating mutation of the prognosis of the tumor. FOXL2 is a transcription factor gene involved in ovarian development and function, whose expression is reduced and which is mutated in the majority of GCTs. FOXL2 appears to play a major role in cell cycle regulation. These recent findings open new pathophysiological insights into GCT development as well as revisitation of granulosa cell and ovarian function.
A 30-year-old woman was diagnosed with a stage IA granulosa cell tumor (GCT) of the ovary in 1979. Following removal of the adnexal mass and complete surgical staging, she remained disease-free for 12 years. In 1991 she underwent a resection of a retroperitoneal mass, confirmed to be a recurrent GCT. Despite adjuvant radiation treatment at the time of recurrence, the patient presented five years later with abdominal pain, and was found to have a second recurrence. Over the next 10 years the patient had multiple recurrences and progressive disease despite surgical resection, cytotoxic, hormonal and targeted chemotherapy treatments. In conclusion, there is no standard management for recurrent GCT of the ovary. We review this patient's treatment in the context of the current literature.
Granulosa cell tumor; Hormonal therapy; Ovarian cancer; Chemotherapy
Granulosa cell tumors (GCTs) are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular model. Immunohistochemistry, Western blot and RT-PCR results showed that the ErbB family of receptors is expressed in human GCT tissues and GCT cell lines. RT-PCR results also indicated that TGFα and EGF are expressed in the human granulosa cells and the GCT cell lines, suggesting that TGFα might regulate GCT cell function in an autocrine/paracrine manner. TGFα stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle progression, and cell migration. TGFα rapidly activated EGFR/PI3K/Akt and mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR, P70S6K and S6 proteins following TGFα treatment. TGFα also rapidly activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFα treatment. Whereas TGFα triggered a transient activation of Akt, it induced a sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells with TGFα resulted in a significant increase in cyclin D2 and a decrease in p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa cell tumorigenesis. In conclusion, TGFα, via multiple signaling pathways, regulates KGN cell proliferation and migration and may play an important role in the growth and metastasis of GCTs.
Granulosa cell tumors (GCTs) comprise 2–5% of ovarian tumors. Serum Müllerian Inhibiting Substance (MIS, also known as anti-Müllerian Hormone, or AMH) levels have been validated as a marker of GCT recurrence and progression. There has been little correlation between serum MIS/AMH levels several clinical parameters in GCTs, including tumor burden. We have performed a retrospective review correlating aggregate tumor mass as reported by pathologic examination or by radiology with serum MIS/AMH levels drawn on the date of examination.
We retrospectively identified 32 GCT patients at our institution over the last 15 years who had serum MIS/AMH measurements. Patients who had serum MIS/AMH measurements within three days of surgery or on the same day as abdominal computerized tomography scan (CT) or magnetic resonance imaging (MRI) were further evaluated.
We found a significant direct correlation between patient serum MIS/AMH levels and gross aggregate tumor mass determined by pathology (slope=15.4±6.06, r=0.65, p<0.04) or by radiographic aggregate tumor mass for all data points identified (slope=0.07±0.03, r=0.33, p<0.04) and after correcting for selection bias (slope=1.45±0.17, r=0.93, p<0.01). We also identified a significant difference between serum MIS/AMH levels between samples drawn the same day as negative and positive abdominal CT or MRI scans (8.16±1.54 vs. 158.7±32.2 ng/ml, p<0.0001).
These data indicate a significant direct correlation between serum MIS/AMH levels and both gross and radiographic aggregate tumor mass in GCT patients. Together with the current literature, the present data argues for a more prominent role for serum MIS/AMH in the management of GCTs.
Introduction. Giant cell tumors (GCTs) of bone are known for their local aggressiveness and high recurrence rate. There are rare cases of multicentric GCT and most are synchronous. We herein review metachronous multicentric GCT reported in the literature. Material and Methods. A MEDLINE, Cochrane, and Google Scholar search was done to collect all cases of multicentric metachronous GCT specifying the clinical, radiological, and histological characteristics of each location and its treatment. Results. A total of 37 multifocal giant cell tumors were found in the literature. 68% of cases of multicentric giant cell tumors occur in less than 4 years following treatment of the first lesion. Thirty-seven cases of multifocal metachronous GCT were identified in the literature until 2012. Patients with multicentric GCT tend to be younger averaging 23. There is a slight female predominance in metachronous GCT. The most common site of the primary GCT is around the knee followed by wrist and hand and feet. Recurrence rate of multicentric GCT is 28.5%. Conclusion. Multicentric giant cell tumor is rare. The correct diagnosis relies on correlation of clinical and radiographic findings with confirmation of the diagnosis by histopathologic examination.
Ovarian granulosa cell tumor (GCT) is a malignant tumor with slow progression. The recurrence of granulosa cell tumor often happens after 5 years, leading to a ‘forgotten tumor’ by the patient. We present the case of a 64-year-old woman with a presentation of left flank pain. An initial computed tomography scan revealed a single tumor with multiple adjacent organ invasions. Surgical intervention was prescribed and the pathological results revealed a metastatic granulosa cell tumor. We also review the literature for the follow-up and further management of this tumor.
Granular cell tumor (GCT) is an uncommon tumor and is believed to be of schwannian origin. GCT is benign but rare malignant cases are recorded. GCT occurs in almost any part of the body. The common sites are the tongue, skin, and subcutaneous tissue. GCT of hand is an extremely rare. Till date only 17 cases are reported in the literature. Preoperative diagnosis of GCT is important, because GCT mimics dermal adnexal tumor in subcutaneous tissue, other soft tissue tumor or inflammatory lesions. GCT is composed of large polygonal cells with eosinophilic granular cytoplasm and these cells are often immunoreactive for the S-100 protein. Fine-needle aspiration cytology has been suggested to be diagnostic modality of choice and this would undoubtedly aid the correct diagnosis. Excision with wide surgical margins is curative for benign GCT. Recurrence and malignant transformation requires regular follow-up. Here, this communication documents a case of cytological diagnosis of the granular cell tumor of hand in a 21-year-old female, clinically suspected to be a dermal adnexal tumor.
Fine-needle aspiration cytology; granular cell tumor; hand; histology; immunohistochemistry
Females of the SWR/Bm (SWR) inbred mouse strain possess a unique susceptibility to juvenile-onset tumors originating from the granulosa cells (GC) of the ovarian follicles. Tumor susceptibility is an inherited, polygenic trait in SWR females, minimally involving an oncogenic Granulosa cell tumor susceptibility (Gct) locus on chromosome (Chr) 4 (Gct1), and two GC tumor susceptibility modifier genes mapped to distinct regions of Chr X (Gct4 and Gct6). Shifts in the frequency of GC tumor initiation in the SWR female population from low penetrance to moderate penetrance, or phenotype switching between GC tumor-susceptible and GC tumor-resistant, is strongly influenced by the allelic contributions at Gct4 and Gct6. In addition to the allele-specific effects, GC tumor susceptibility is controlled by the mode of X-linked transmission with a dominant, paternal parent-of-origin effect. We took advantage of the robust paternal effect with a recombinant male progeny testing strategy to resolve the Gct4 locus interval to 1.345 million base (Mb) pairs. Based on the mapping resolution and the phenotype sensitivity to endogenous and exogenous androgen exposure, a promising candidate for Gct4 identity is the androgen receptor (Ar) gene. We explored the mechanism of allelic variation for Ar between SWR (low penetrance allele) and SJL/Bm (SJL) (moderate penetrance allele) using an SWR.SJL-X congenic strain resource and a quantitative gene expression method. We report the low GC tumor penetrance allele of the SWR strain correlates with significantly reduced Ar transcript levels in the female ovary at the pubertal transition.
granulosa cell tumor; tumor susceptibility allele; parent-of-origin effect
Giant cell tumor (GCT) is a relatively rare neoplasm. In GCT, the bone affection of the axial skeleton is extremely rare. Most GCT arises in the meta-epiphyseal ends of the long bones. Its peak incidence is between 30 to 40 years of age. GCT is usually classified as benign, but shows locally aggressive behavior and may occasionally undergo a malignant transformation. The patients with GCT in the spine often complain of the lower back pains, as the tumors primarily involve the sacrum. We report a case of an adolescent female complaining of the upper back pain with a sudden weakness of the lower extremities, later diagnosed with the GCT of the T2 vertebra. The present patient showed American Spinal Injury Association Impairment Scale (AIS) D before the surgery, which changed to AIS E after the treatments including the surgery, radiation therapy and rehabilitation.
Giant cell tumor; Spinal cord injuries
Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-κB) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to IκB degradation and activation of NF-κB. NF-κB activation was confirmed by nuclear localization of NF-κB p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-κB signaling attenuated LPS-induced TNFαplus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-κB signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-κB does not sensitize GCTs to TRAIL or cisplatin.
Granulosa cell tumor; Toll-like receptor; TLR; ovary; LPS; lipopolysaccharide
Malignant giant cell tumor (GCT) of bone is a rare tumor with debilitating consequences. Patients with GCT of bone typically present with mechanical difficulty and pain as a result of bone destruction and are at an increased risk for fracture. Because of its unusual occurrence, little is known about the epidemiology of malignant GCT of bone. This report offers the first reliable population-based estimates of incidence, patient demographics, treatment course and survival for malignancy in GCT of bone in the United States. Using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program, we estimated the overall incidence and determinants of survival among patients diagnosed with malignant GCT of bone from 1975–2004. Cox proportional hazards regression was used to evaluate demographic and clinical determinants of survival among malignant GCT cases. Based on analyses of 117 malignant GCT cases, the estimated annual incidence in the United States was 1.6 per 10,000,000 persons per year. Incidence was highest among adults aged 20 to 44 years (2.4 per 10,000,000 per year) and most patients were diagnosed with localized (31.6%) or regional (29.9%) disease compared to distant disease (16.2%). Approximately 85% of patients survived at least 5 years, with survival poorest among older patients and those with evidence of distant metastases at time of diagnosis. The current study represents the largest systematic investigation examining the occurrence and distribution of malignancy in GCT of bone in the general U.S. population. We confirm its rare occurrence and suggest that age and stage at diagnosis are strongly associated with long-term survival.
giant cell tumor of bone; surveillance; epidemiology and end results; descriptive epidemiology; incidence; survival; osteosarcoma.
Extragonadal localization of germ cell tumors (GCTs) is rare; to the best of our knowledge, a location in the soft tissue of the arm has never been previously reported in the literature.
We report the case of a 37-year-old man who presented with a primary malignant mixed non-seminomatous GCT (teratocarcinoma variety) in the right arm, treated by a combination of cisplatin-based chemotherapy and surgery. After 18 months of close follow-up, no locoregional recurrence or distant metastases have been detected.
A combination of chemotherapy and surgery is the most appropriate treatment strategy for extragonadal GCTs, to ensure both local and systemic control.
Chemotherapy; Embryonic carcinoma; Extragonadal; Mixed germ cell tumors; Surgery; Teratoma
Giant cell tumor (GCT) is usually a benign but locally aggressive primary bone neoplasm in which monocytic macrophage/osteoclast precursor cells and multinucleated osteoclast-like giant cells infiltrate the tumor. The etiology of GCT is unknown, however the tumor cells of GCT have been reported to produce chemoattractants that can attract osteoclasts and osteoclast precursors. Rarely, GCT can originate at extraosseous sites. More rarely, GCT may exhibit a much more aggressive phenotype. The role of chemotherapy in metastatic GCT is not well defined.
We report a case of an aggressive GCT of the uterus with rapidly growing lung metastases, and its response to chemotherapy with pegylated-liposomal doxorubicin, ifosfamide, and bevacizumab, along with a review of the literature.
Aggressive metastasizing GCT may arise in the uterus, and may respond to combination chemotherapy.
Background. Granulosa cell tumors (GCTs), representing ~2% of ovarian tumours, are poorly understood neoplasms with unpredictable and undetermined biological behaviour. Design. 5 unusual presentations of GCT and a retrospective 14-year (1997–2011) surgical pathology review based on patient sex, age, tumour type and concurrent pathology findings are presented to discuss the “myths and realities” of GCTs in the context of relevant evidence-based literature. Results. The 5 index cases included (1) a 5 month-old boy with a left testicular mass, (2) a 7-day-old neonate with a large complex cystic mass in the abdomen, (3) a 76-year-old woman with an umbilical mass, (4) a 64-year-old woman with a complex solid-cystic pelvic mass, and (5) a 45 year-old woman with an acute abdomen. Pathological analysis confirmed the final diagnosis as (1) juvenile GCT, (2) macrofollicular GCT, (3) recurrent GCT 32 years later, (4) collision tumour: colonic adenocarcinoma and GCT, and (5) ruptured GCT. Conclusion. GCT is best considered as an unusual indolent neoplasm of low malignant potential with late recurrences that can arise in the ovaries and testicles in both the young and the old. Multifaceted clinical presentations coupled with the unpredictable biological behaviour with late relapses are diagnostic pitfalls necessitating a high degree of suspicion for accurate clinical and pathological diagnosis.
Granular cell tumors (GCT) of the head and neck are not uncommon; however, involvement of the cervical esophagus is rare. Characterized by an infiltrative growth pattern, these benign tumors are historically difficult to surgically excise and are radioresistant. We present here a case of dysphagia caused by a GCT of the cervical esophagus. Work up with ultrasound-guided fine needle aspiration was suggestive of a GCT due to the presence of cohesive cells with granular cytoplasm that were S-100 and CD68 positive with immunostaining, and PAS positive with histochemistry. Resection required removal of a portion of the muscular wall of the esophagus sparing the overlying mucosa. The patient is currently asymptomatic and without recurrence after 10 month follow-up. Review of the literature revealed 19 reports of cervical esophageal GCTs. There is a female preponderance (75 %), with an average age of 41 years. Dysphagia and weight loss are the most common presenting symptoms. The average tumor size on presentation was 2.7 cm, with symptomatic tumors being significantly larger than asymptomatic lesions; the latter was present in 25 % of patients. Concurrent GCTs in the upper aerodigestive tract were identified in 35 % of cases. Approximately 30 % of tumors required segmental cervical esophageal resection. The purpose of this report is to describe the epidemiology and treatment of GCTs of the cervical esophagus. Lesions should be addressed early with complete surgical excision to prevent growth necessitating more morbid surgery. Due to the high rate of concurrent GCTs, upper endoscopy is advised in the workup of these patients.
Granular cell tumor; Cervical esophagus; Management; Dysphagia
Esophageal granular cell tumors (GCTs) are rare tumors of the esophagus. We evaluated the clinical and pathologic features of 9 esophageal GCT patients (5 men and 4 women) from our institute and reviewed the related disease literature. Patient age ranged from 25 to 53 years (mean: 41 years). All the patients were asymptomatic or presented with non-specific symptoms. Most GCTs occurred in the distal esophagus and were less than 6 mm in diameter. Computational analysis showed that the average gray-scale endoscopic ultrasound images of esophageal GCTs were greater than that of esophageal leiomyomas. Eight patients were treated by endoscopic resection, and 1 patient underwent surgical excision. No post-therapy recurrence or metastasis developed during follow-up (mean: 36.4 mo, range: 1-72 mo).
Esophageal granular cell tumor; Endoscopic ultrasonography; Computer images analysis
Objective: To discuss the current management options for giant-cell tumors (GCTs) involving the temporal bone and present two case reports and a review of the literature. Method: In a tertiary-care academic medical center, two patients with GCTs of the temporal bone were evaluated and managed. The patients underwent gross total resection and curettage of GCTs involving the temporal bone. Afterward, both patients were evaluated for postoperative complications as well as for recurrence. Results: Two patients underwent operative excision using curettage. Clinical and radiographic studies demonstrated no evidence of recurrence with 3 years of follow-up in one patient and 10 years of follow-up in the second patient. Conclusion: Based on these results, we concluded that gross total removal and curettage of GCTs in the temporal bone is a viable treatment option. This finding is contrary to previous studies.
Temporal bone; giant-cell tumors; skull base
Giant cell tumour of bone (GCT) is a relatively rare benign bone tumour more frequent in young people (20–40 years). Histologically, two cell types are represented, stromal cells of osteoblastic origin and a distinctive osteoclast-like population probably of monocytic origin. GCTs can be aggressive and they recur locally in up to 50% of cases; up to 5% of GCTs metastasise to the lungs and spontaneous transformation to a high-grade malignancy occurs in 1–3% of patients. The aetiology of GCT is not known, and no risk factors have been recognised, although familial clustering of both Paget’s disease and GCT has been reported.
GCTs account for approximately 3–5% of primary bone tumours. GCT is rarely multicentric and usually occurs at the epiphyses of long bones, but may also affect other bones.
There are few randomised, prospective clinical trials available to guide clinical management of GCT. Recent developments have led to evaluation of newer therapeutic agents, including biphosphonates and denosumab, with encouraging results. We report the case of a 66-year-old woman affected by GCT. In 1985 the patient, then 41 years old, presented a cystic lesion on her left tibia, which was removed surgically. This lesion relapsed two years later. Therefore the patient was hospitalised and received a diagnosis of “multicentric giant cell bone lesions” (limb-girdle, sternum, mandible, ribs), confirmed by histological examination. These lesions showed hyperactivity on bone scintigraphy. Plain radiographs demonstrated destructive lytic lesions. Blood and urinary examinations showed markedly elevated levels of bone alkaline phosphatase and urine pyridinoline and there was persistent bone pain. In 1993 normocalcaemic primary hyperparathyroidism was diagnosed and an adenoma was removed, with no relapse of the disease. Subsequently the patient started clodronate therapy, i.v., followed by alendronate-neridronate per os and clodronate i.m. for about nine years. Biphosphonate therapy caused a modest and transient decrease in bone indexes. Initial bone lesions were unchanged on computed tomography 25 years after diagnosis, but new bone lesions had appeared. MEN1 gene and CasR analyses were negative.
This is a rare case of a patient affected by multicentric giant cell tumours with a 25-year follow up. A slow progression of the lesion is documented, as well as the absence of significant effect of biphosphonate therapy.
Granulosa cell tumor (GST) is a sex-cord/stromal neoplasm of the gonads, more commonly arising in the ovaries, while approximately 80 cases have been reported in the testes. Out of these, 30 cases were of the adult type, while the remainder 50 cases were of the juvenile type. The latter mostly concerned infants and followed a benign course. However, the adult type testicular GCTs may be potentially malignant as it also happens in female patients with such neoplasms. We present a case of an adult type GCT located at the left testis. The patient was subjected to total orchiectomy and received no further treatment. Histology showed typical GCT histomorphology with Call-Exner bodies in some places. The immunoprofile of the tumor was CD99 (+), calretinin (+), inhibin (+), alpha smooth muscle actin (+), vimentin (+), ER (−), PR (−), keratin AE1/AE3 (−), alpha fetoprotein (−), CD117 (−), and placental alkaline phosphatase (−). Two years after surgery, the patient is alive and well with no signs of recurrence.
Background and purpose
Giant cell tumor (GCT) of the small bones (small-bone GCT) is usually rare and considered somewhat different from conventional GCT. The purpose of this study was to investigate and report the clinicopathological features of 11 cases with small-bone GCT.
Materials and methods
Patient information was obtained with the help of questionnaires. X-rays and paraffin blocks obtained from several institutions were clinically, radiographically, and histologically evaluated.
Small-bone GCT was observed in younger patients compared to conventional GCT; 5 of the 11 (45%) patients were below 20 years of age, whereas the corresponding figure for all GCT patients is 16% in Japan. Excessive cortical bone expansion is a special feature. There were two cases of recurrence and one case of lung metastasis; the primary lesion was in the hand for all three cases. In contrast, no primary lesion of the foot recurred or metastasized. Varying degrees of positive p63 immunostaining were observed in all examined cases (n = 9) of small-bone GCT but were negative in case of giant cell reparative granuloma (GCRG) and solid variant of aneurysmal bone cyst (ABC). One case that demonstrated high-intensity positive staining had two episodes of recurrence.
Small-bone GCT tends to develop in younger patients than does conventional GCT. Primary GCTs of the hand may be biologically more aggressive than those of the feet. The p63 immunostaining may be useful not only for differential diagnosis but also for prognostication of small-bone GCT.
clinicopathological study; giant cell tumor; p63 immunostaining; small bone
Adult granulosa cell tumors of the ovary (GCTs) are sex cord stromal tumors of unpredictable behaviour. Up to now, the prediction of the relapsing/malignant potential remains difficult. CD56 (NCAM) in GCTs was previously described in only two studies. However, the expression of its isoforms was not examined.
30 GCTs (16 primaries, 14 relapses) were investigated immunohistochemically with antibodies against Pan-CD56 (CD56Pan) and the isoform with 140/180 kDa length (CD56140/180 kDa). The reaction was assessed with respect to percentage of positive cells and intensity of staining.
In all GCTs, CD56Pan was expressed, but differences were found between primaries and relapses. The percentage of CD56Pan positive tumor cells was lower in relapses, whereas CD56140/180 kDa showed a higher staining intensity in the latter.
Expression of CD56 is an additional sensitive and helpful immunohistochemical tool for histopathologists diagnosing a GCT. It does not seem possible to provide a validly individual risk assessement. However, the different expression of CD56 isoforms might indicate important changes in the course to a more malignant behaviour.
Granular cell tumor (GCT) is a rare and usually benign lesion of neural / schwannian origin, most frequently found in middle-age women. The appendicular involvement is extremely rare: in over half a century only twelve cases have been reported in the literature, the patients living in America and Europe. Hitherto, no cases are documented from Africa, Asia and Oceania and no cases of malignant GCTs of the appendix have been reported.
Most patients were diagnosed preoperatively as having acute appendicitis, whereas in three patients the tumor was incidentally detected during major abdominal surgery. The GCTs were equally distributed between mid-appendix and tip, where lymphoid tissue is more abundant and the anatomical nerve supply is progressively reduced. Moreover, the appendix surrounding the GCTs is characterized by the presence of chronic inflammatory cells (histiocytes, plasmocytes, eosinophils, mastocytes) and, therefore, a chronic inflammation of the appendix may be an antecedent condition favouring the appearance of GCTs. The GCT of the appendix appears so to be a lesion that reflects local reactive changes in the neural / schwannian cells, rather than being a genuine neoplasm. We describe the smallest GCT of the appendix ever reported, with a detailed literature review supporting its reactive origin in the lymphatic tissue-rich sites, such as ileo cecal appendix.
Granular cell tumor; Ileocecal appendix; Chronic appendicitis; Segmented peritonitis; Oncologic management
Aberrant ovarian granulosa cell proliferation and apoptosis may lead to granulosa cell tumors (GCT), the pathogenesis of which involves transcription factors GATA4, FOXL2, and SMAD3. FOXL2 gene harbors a point mutation (C134W) in a vast majority of GCTs. GATA4 is abundantly expressed in GCTs and its expression correlates with poor prognosis. The TGF-β mediator SMAD3 promotes GCT cell survival through NF-κB activation, and interacts with FOXL2. Here, we find that the expression patterns of these factors overlap in the normal human ovary and 90 GCTs, and positively correlate with each other and with their mutual target gene CCND2, which is a key factor for granulosa cell proliferation. We have explored the molecular interactions of FOXL2, GATA4, and SMAD3 and their roles in the regulation of CCND2 using co-immunoprecipitation, promoter transactivation, and cell viability assays in human GCT cells. We found that not only SMAD3, but also GATA4 physically interact with both wild type and C134W-mutated FOXL2. GATA4 and SMAD3 synergistically induce a 8-fold increase in CCND2 promoter transactivation, which is 50% reduced by both FOXL2 types. We confirmed that wild type FOXL2 significantly decreases cell viability. Interestingly, GATA4 and SMAD3 caused a marked reduction of GCT cell apoptosis induced by wild type FOXL2. Thus, the effects of GATA4 and SMAD3 on both cell viability and apoptosis are distinct from those of wild type FOXL2; a perturbation of this balance due to the oncogenic FOXL2 mutation is likely to contribute to GCT pathogenesis.
The pre-operative embolization of hypervascular spinal tumors is often performed to decrease intraoperative blood loss and facilitate tumor resection; however, few studies have been published on its effectiveness in giant cell tumors (GCT) of the sacrum and spine. The purpose of the present study was to investigate the value of surgical excision with pre-operative transarterial embolization for GCTs of the sacrum and spine, and to evaluate the follow-up outcomes. A retrospective study was performed on 28 patients with GCTs of the sacrum and spine, who underwent surgical treatment combined with pre-operative transarterial embolization between June 1995 and August 2011. The intraoperative blood loss, transfusion, duration of surgery, treatment, local recurrence, complications, follow-up status and functional outcome were reviewed. The average follow-up period was 86.3 months (range, 12–193 months). All the patients were treated with intralesional resection without any intraoperative shock or fatalities. The average intraoperative level of blood loss was 1,528.6 ml (range, 400–5,800 ml), the average transfusion volume was 1,514.3 ml (range, 400–6,000 ml) and the average duration of surgery was 225.4 min (range, 120–470 min). In total, eight (28.6%) patients developed recurrence and two patients succumbed. A total of eight (28.6%) patients experienced complications and 24 (85.7%) retained normal neurological function. Pre-operative embolization significantly decreases intraoperative blood loss and facilitates the maximal removal of the tumor. Pre-operative embolization followed by intralesional resection is able to achieve satisfactory local control and clinical outcomes. It is an effective technique for excising GCTs of the sacrum and spine.
giant cell tumor; blood loss; spine; sacrum; embolization