Sarcomatous Component Research Articles

Diagnostic implications of IDH1-R132H and OLIG2 expression patterns in rare and challenging glioblastoma variants

Recent work has demonstrated that nearly all diffuse gliomas display nuclear immunoreactivity for the bHLH transcription factor OLIG2, and the R132H mutant isocitrate dehydrogenase 1 (IDH1) protein is expressed in the majority of diffuse gliomas other than primary glioblastoma. However, these antibodies have not been widely applied to rarer glioblastoma variants, which can be diagnostically challenging when the astrocytic features are subtle. We therefore surveyed the expression patterns of OLIG2 and IDH1 in 167 non-conventional glioblastomas, including 45 small cell glioblastomas, 45 gliosarcomas, 34 glioblastomas with primitive neuroectodermal tumor-like foci (PNET-like foci), 23 with an oligodendroglial component, 11 granular cell glioblastomas, and 9 giant cell glioblastomas. OLIG2 was strongly expressed in all glioblastomas with oligodendroglial component, 98% of small cell glioblastomas, and all granular cell glioblastomas, the latter being particularly helpful in ruling out macrophage-rich lesions. In 74% of glioblastomas with PNET-like foci, OLIG2 expression was retained in the PNET-like foci, providing a useful distinction from central nervous system PNETs. The glial component of gliosarcomas was OLIG2 positive in 93% of cases, but only 14% retained focal expression in the sarcomatous component; as such this marker would not reliably distinguish these from pure sarcoma in most cases. OLIG2 was expressed in 67% of giant cell glioblastomas. IDH1 was expressed in 55% of glioblastomas with oligodendroglial component, 15% of glioblastomas with PNET-like foci, 7% of gliosarcomas, and none of the small cell, granular cell, or giant cell glioblastomas. This provides further support for the notion that most glioblastomas with oligodendroglial component are secondary, while small cell glioblastomas, granular cell glioblastomas, and giant cell glioblastomas are primary variants. Therefore, in one of the most challenging differential diagnoses, IDH1 positivity could provide strong support for glioblastoma with oligodendroglial component, while essentially excluding small cell glioblastoma.

Genetic and pathologic evolution of early secondary gliosarcoma

Gliosarcoma is a subset of glioblastoma with glial and mesenchymal components. True secondary gliosarcomas (i.e. progressing from lower-grade precursors) in the absence of radiation therapy are very rare. We report the unique case of a 61-year-old male who developed a fibrillary astrocytoma (WHO grade II). In the absence of adjuvant therapy the tumor recurred 3years later as a gliosarcoma comprising an infiltrating glial component and a curious, early high-grade sarcomatous component surrounding intratumoral vessels. DNA was extracted from formalin fixed paraffin-embedded tissues from the precursor low-grade glioma and from the glioma and sarcomatous components at progression. Samples were hybridized separately to a 300k Illumina SNP array. IDH1(R132H) mutant protein immunohistochemistry was positive in all tissue components. Alterations identified in all samples included dup(1)(q21q41), del(1)(q41qter), del(2)(q31.1), del(2)(q36.3qter), del(4)(q35.1qter), dup(7)(q22.2q36.3), del(7)(q36.3qter), del(9)(p21.3pter), dup(10)(p13pter), del(10)(q26.13q26.3), dup(17) (q12qter), and copy neutral LOH(20)(p11.23p11.21). The recurrent tumor had additional alterations, including del(3)(p21.31q13.31), del(18)(q21.2qter), and a homozygous del(9)(p21.3)(CDKN2A locus) and the sarcoma component had, in addition, del(4)(p14pter), del(6)(q12qter), del(11)(q24.3qter), and del(16)(p11.2pter). In conclusion, unique copy number alterations were identified during tumor progression from a low-grade glioma to gliosarcoma. A subset of alterations developed specifically in the sarcomatous component.

Gefitinib Treatment for Pulmonary Sarcomatoid Carcinoma Driven by an EGFR Mutation: Two Cases

Sarcomatoid carcinoma of the lung is defined as a group of poorly differentiated non-small cell carcinomas that contain a component of sarcoma or a sarcoma-like element. Most sarcomatoid carcinomas are known to have a poor prognosis. We describe a 45-year-old female never smoker and 49-year-old female never smoker with sarcomatoid carcinomas of the lung that expressed a specific EGFR mutation: microdeletion of exon 19. Their cancers progressed rapidly, despite appropriate conventional chemotherapy. After they took the EGFR-targeted agent gefitinib, there was a dramatic reduction in tumor size. Sarcomatoid carcinoma of the lung is a rare cancer whose pathogenesis is not well understood. According to these cases, the EGFR mutation could be a driver mutation and the potential therapeutic target of EGFR-targeted agents for sarcomatoid carcinoma in lung cancer patients, especially never smokers. (Korean J Med 2013;84:446-451)

Primary intratesticular rhabdomyosarcoma in pediatrics

Testicular sarcomas constitute only 1–2% of all testicular tumors and are mostly associated with germ cell tumor. Primary intratesticular rhabdomyosarcoma is rare and only 14 cases have been reported in the literature till date. It should be differentiated from germ cell tumor with sarcomatous component, other intratesticular spindle-cell sarcomas and paratesticular rhabdomyosarcoma. Accurate diagnosis and early treatment is essential as it is an aggressive tumor with high metastatic potential and poor prognosis. Orchidectomy is the treatment of choice. Chemo-radiotherapy is recommended in case of recurrence and metastasis.

Clinico-pathological spectrum of primary ovarian malignant mixed mullerian tumors (OMMMT) from a tertiary cancer institute: A series of 27 cases

To study the clinico-pathological characteristics of primary ovarian malignant mixed mullerian tumor (OMMMT) and assess the prognostic factors associated with treatment outcome and survival. The pathology database was searched for primary ovarian carcinosarcoma diagnosed and/or managed at our institute from period of January 2004 to July 2010. The histological sections were reviewed, with emphasis on type and grade of epithelial and sarcomatous components. The medical records were retrospectively analyzed for clinical details and follow up. A total of 27 cases of primary ovarian carcinosarcoma were identified. The median age at diagnosis was 51 years. Fourteen patients had advanced stage (stage III and IV) at presentation. Cytoreductive surgery was done in 18 cases, and 7 had received upfront chemotherapy. Histologically, 10 cases had epithelial predominance (> 50% epithelial component) and 11 had sarcoma predominance. The most frequent epithelial component was endometroid type, and most common sarcoma component was rhabdomyosarcomatous. Hyaline droplets within sarcomatous stroma were seen prominently in 15 cases. Three cases showed germ cell /yolk sac-like areas. Eighteen cases had follow up with a median of 15 months (4-40 months). The recurrence-free survival in advanced stage and sarcoma predominant was 10.5 months in comparison to 13 months in early stage and epithelial predominant OMMMT. Primary ovarian carcinosarcoma is a rare biphasic malignancy with variable proportions of epithelial and spindle elements. Presence of hyaline droplets within spindle sarcoma in a biopsy from ovarian mass should alert the pathologists regarding MMMT. Advanced stage, suboptimal cytoreduction, and sarcoma predominant tumors are likely to have a worse outcome in ovarian MMMT.

Carcinosarcoma of the Stomach: A Case Report

Carcinosarcoma is a rare malignant, biphasic tumor comprised of carcinoma and sarcoma components. In the gastrointestinal tract, carcinosarcoma is most frequently seen in the esophagus and rarely in the stomach. We report a 51-year-old female patient with 2-month-history of epigastric pain and dyspepsia. Endoscopic finding revealed a huge ulcerative lesion that infiltrated from the antrum to the mid-body. An endoscopically taken biopsy revealed poorly differentiated malignant round cell neoplasm. After the palliative subtotal gastrectomy, immunohistochemical studies showed two positive reactions for the epithelial marker and mesenchymal marker. Based on the above findings, the patient was diagnosed with gastric carcinosarcoma. The immunohistochemical analysis is a critical method in making an accurate diagnosis of carcinosarcoma.

33. Basal cell carcinosarcoma: a report of three cases and review of the literature

The term ‘carcinosarcoma’ has been used for a range of morphologically distinct biphasic cutaneous tumours. These include squamous cell carcinoma with spindle cell or sarcomatoid components, malignant adnexal tumours with epithelial and mesenchymal elements and Merkel cell carcinoma with sarcomatoid components. The term has also been used to refer to monophasic carcinomas with a ‘sarcoma-like’ morphology, tumours also termed ‘sarcoma-toid carcinoma’. Lesions showing basal cell carcinoma with sar-comatoid stroma are rare, with only small series and single cases reported. We report the clinical and pathological features of three cases of this entity, retrieved from the files of three pathology practices, and review reported cases from the literature. All three of our cases occurred on the ear of elderly men and showed an epithelial component with typical features of nodular basal cell carcinoma, with an additional component of infiltrating basal cell carcinoma in one. In addition, all three showed a distinct admixed component of spindle cell sarcoma without features of specific differentiation. In one case there was a minor admixed component with an osteo-sarcomatous appearance, and one showed scattered tumour giant cells. Despite relatively high reported rates of local recurrence and metastasis for ‘carcinosarcoma’ as an unrefined entity, it appears that the sub-group of basal cell carcinosarcoma has a relatively good prognosis, with adequate local excision being curative in the majority of cases. Recognition of this entity is critical for accurate diagnosis and its separation from other types of carcinosarcoma may have significant prognostic implications.

癌肉腫，扁平上皮癌，腺様成分を伴った食道神経内分泌癌の1例

癌肉腫，扁平上皮癌，腺様成分を伴った食道神経内分泌癌の1例

Carcinosarcoma in dermoid cyst of ovary: An extremely rare malignant transformation

We report here a case of carcinosarcoma arising from dermoid cyst of ovary comprising of squamous cell carcinoma and pleomorphic sarcoma with focal myogenic differentiation.A 52-year-old female presented with left lower abdominal pain and a large pelvic mass. Ultrasonography revealed a large left adnexal cystic mass with fluid level and a small solid nodule [Figure 1]. Patient underwent total hysterectomy with bilateral salpingo-oophorectomy. The ovarian tumor was large measuring 18  12 10 cm. It was unilocular cystic mass filled with hair and yellow colored cheesy material. The thickness of cyst wall was 0.5-1.5 cm and a solid area measuring 3 cm in diameter was seen in one pole [Figure 2]. The left ovary appeared normal. The uterus was atrophic with keratinized cervix. Histopathological examination of the cyst wall showed a stratified squamous epithelial lining with focal dysplastic change and transition to infiltrating carcinoma with underlying dermal appendages. Hematoxylin and eosin stained sections from the solid area showed a malignant tumor with two distinct components. One of the components was epithelial showing diffuse squamous differentiation with extensive keratinization [Figure 3]. There was nuclear anaplasia and atypical mitosis. The other component revealed features of pleomorphic spindle cell sarcoma with marked pleomorphism and hyperchromasia, [Figure 3] frequent mitoses and necrosis. The epithelial and mesenchymal components were closely intermixed without well-demarcated boundaries. On immunohistochemistry, the malignant epithelial cells were reactive for high molecular weight keratin [Figure 4a] and P63 protein [Figure 4b] while the pleomorphic spindle cell sarcomatous component showed diffuse positivity for vimentin [Figure 4c] and focally for smooth muscle actin [Figure 4d]. Desmin, S100 protein and CD10 were negative in both components.The present case was a large ovarian cyst with characteristic squamous epithelial lining as described by Arora and Haldane who found adenocarcinoma in combination with sarcoma in dermoid cyst of ovary.

Autopsy: failed intubation – what was the cause?

Aim and Methods A 77-year-old man presented to the Emergency Department with profound shortness of breath. The intubation failed due to upper airway obstruction and subsequently he underwent cri-cothyroidotomy. He had a cardiac arrest for up to 20 minutes in the Emergency Department. He was transferred to the Intensive Care Unit. He showed evidence of global ischaemia of the brain and his life support equipment was stopped after 3 days. His past medical history included beta thalassaemia and C3 to C7 laminectomy for severe cervical myelopathy 4 months prior to his death. Results The autopsy revealed a polypoid laryngeal tumour 3.2 cm in maximum dimension arising from the right vocal cord. The tumour extended to the glottic and supraglottic spaces. The superior aspect of the tumour was visible behind the epiglottis. Histologically, the tumour was a carcinosarcoma with squamous cell carcinoma and osteosarcoma component with sarcomatous component overgrowth. Discussion Carcinosarcoma of the larynx is a very rare tumour predominantly occurring in elderly males. They are rapidly growing polypoid tumours which often present with acute airway obstruction. In this case, the retrospective review of the MRI performed 4 months ago for the cervical laminectomy showed a 0.7 cm nodule on the vocal cord.

Multiple carcinosarcomas of the esophagus and stomach

Carcinosarcoma is an uncommon biphasic malignant neoplasm consisting of both carcinomatous and sarcomatous components. We report a case of an 84-year-old male with multiple carcinosarcomas occurring in the esophagus and stomach. Endoscopically, a bulky pedunculated polypoid lesion was observed in the middle of the esophagus and a huge discoid lesion in the lesser curvature. The patient received esophageal endoscopic mucosal resection, and the specimen measured 4×2.5×1.5 cm. Microscopically, the esophageal tumor consisted of several polymorphic spindle cells mixed with squamous cells, while the gastric biopsies revealed carcinomatous cells with evident abnormal karyokinesis and polymorphous spindle cells. Immunohistochemically, the resected tumor stained positively for the epithelial markers, epithelial membrane antigen (EMA) and cytokeratin 19 (CK 19), and the mesenchymal markers, smooth muscle actin (SMA) and vimentin. The gastric lesion stained positively for CK AE1/AE3, actin and vimentin, but was negative for EMA. Both lesions were positive for neuron specific enolase (NSE), demonstrating neuroendocrine differentiation. The patient succumbed seven months after being discharged from hospital. To our knowledge, this is the first case in the literature that describes multiple carcinosarcomas arising from the esophagus and stomach. A review of the available literature is also presented.

Sarcomatoid carcinoma of the remnant stomach: report of a case

We herein report a case of sarcomatoid carcinoma that developed in a remnant stomach. A 76-year-old male with a history of distal gastrectomy for a duodenal ulcer 28years earlier underwent investigation for a tumor in the remnant stomach. An endoscopic survey showed a round elevated tumor measuring 6cm in diameter, and a biopsy specimen suggested carcinosarcoma. A total gastrectomy of the remnant stomach was performed, and the excised tumor was identified to be a malignant neoplasm consisting of both carcinomatous and sarcomatous components. A diagnosis of sarcomatoid carcinoma was made since the epithelial markers were positive even in the mesenchymal elements of the tumor. To our knowledge, only 4 cases of sarcomatoid carcinoma of the stomach have been reported in the English literature so far.

P2-047 - A Gastric Carcinosarcoma Patient who Underwent Chemotherapy

ABSTRACT Gastric carcinosarcoma is very rare, and there is no standard chemotherapy regimen. We report a case of a 61-year-old woman with gastric carcinosarcoma associated with the liver and lymph node metastases. She underwent distal gastrectomy due to uncontrollable bleeding from the gastric tumor. Histopathological examination of the resected specimen revealed adenocarcinoma and sarcomatous component with spindle-shaped tumor cells accompanied by cartilage formation. She was diagnosed as carcinosarcoma of the stomach with distant metastases and underwent chemotherapy with S1–cisplatin. Although CT scan revealed shrinkage of the metastatic lesions after one course of the treatment, the lesions progressed after four courses. She underwent treatment with doxorubicin–ifosfamide as second-line chemotherapy and docetaxel as third-line chemotherapy. The metastatic lesions progressed rapidly and she died 9 months after diagnosis.

Carcinomes sarcomatoïdes pulmonaires

Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about 1 % of non-small cell lung carcinoma (NSCLC). In 2004, World Health Organization classification united under this name all the carcinomas with sarcomatous or sarcomatous-like component with spindle cell or giant cell appearance. There are five subtypes: spindle cell carcinoma, giant cell carcinoma, pleomorphic carcinoma, carcino-sarcoma and pulmonary blastoma. Clinical characteristics are not specific from the others subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastasis are frequent with atypical locations such as peritoneal or retroperitoneal sites. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here, we present a review of litterature in order to better describe these tumors.

ONGOING TESTICULAR TUMOUR OF 8 YEARS WITHOUT LOCO REGIONAL SPREAD – AN ENIGMA FOR TREATMENT

Spermatocytic seminoma is a rare testicular germ cell tumor associated with a good prediction. Spermatocytic seminoma with sarcomatous transformation is an extremely rare with only few cases reported. The presence of a sarcomatous component is associated with an aggressive behaviour, metastasis, and poor prognosis. We present an unusual case of a spermatocytic seminoma with rhabdomyosarcomatous transformation in a long-standing testicular swelling of 8 years.

Could Spindle Cell Lung Carcinoma be Considered and Treated as Sarcoma, According to its Clinical Course, Morphology, Immunophenotype and Genetic Finding?

The actual nature of spindle cell carcinoma has been debated extensively because of its rarity. It carries a poor prognosis, even when early-stage disease is diagnosed and resected. In view of the rarity and the significance of the histological diagnosis, we report a patient with rapidly progressing spindle cell lung carcinoma with soft tissue metastasis. Diagnosis was confirmed by immunohistochemistry finding. Analysis of the TP53 gene mutations by polymerase chain reaction and DNA sequencing revealed insertion of single thymine resulting in frameshift mutation in the exon 8. Prognosis of spindle cell lung carcinoma might be determined by the sarcoma component of the tumor and, based on that, we wonder if this type of lung carcinoma could be followed-up and treated by strategies for soft tissue sarcomas, because of its rapid, sarcomatous type of growth, beside the properly lung carcinoma oncological treatment.

Metaplastic carcinoma of the right breast and simultaneous giant ovarian teratoma: a case report

We describe here a female patient who presented with a breast mass and giant abdominal mass. Fine needle aspiration cytology of the breast mass and histological examination after modified radical mastectomy confirmed metaplastic carcinoma of the breast. The epithelial components were formed by infiltrating ductal carcinoma with poor differentiation, and the sarcomatous components were formed by fibrosarcoma and osteosarcoma. Histological examination of the abdominal mass confirmed ovarian teratoma. The patient underwent modified radical mastectomy of the right breast and laparoscopic excision of the abdominal mass in the lower right quadrant. Having underwent six courses of chemotherapy, the patient is now in her tenth month after surgery and under follow-up, and she has no relapsed disease. These two diseases have never seen in one patient before. The case we report here provides some new data for research and clinical experience and it may also provide a new insight into the relationship between metaplastic breast carcinoma and ovarian teratoma.

Trichoblastic Sarcoma With Osteosarcomatous Differentiation

Only one description of trichoblastic sarcoma exists in the literature. Here, we present the first case of trichoblastic sarcoma with heterologous osteosarcomatous differentiation. Biospy 1 demonstrated an intermediate-grade trichoblastic sarcoma with pleomorphic cells and atypical mitotic figures observed only in the stroma. The epithelium contained no malignant cells. The histologic morphology was reminiscent of an intermediate-grade phyllodes tumor of the breast. Biopsy 2, an excisional biopsy taken 7 months later, showed a high-grade sarcoma with osteosarcomatous differentiation. Immunohistochemistry performed on both specimens showed positive CD10 and bcl-2 staining in the sarcomatous component; p63 was positive in the benign epithelium only. p53 was negative in both the benign epithelium and the malignant stroma. Ki-67 labeling was approximately 10% in both components. Specimen 3, a complete rhinectomy performed 3 months later, showed a poorly differentiated sarcoma. Six months following his rhinectomy procedure, multiple pulmonary nodules consistent with metastatic disease were detected on chest computed tomography. This is the first case report documenting the evolution of an intermediate-grade trichoblastic sarcoma to a high-grade lesion with osteosarcomatous differentiation, to a poorly differentiated sarcoma. The tumor morphologically resembles malignant phyllodes tumor of the breast. Our case is the first to show negative p53 and positive bcl-2 staining in a trichoblastic sarcoma. We propose that cutaneous trichoblastic sarcoma is pathogenetically analogous to phyllodes tumors of the breast, adenosarcoma of the uterus, or ameloblastoma of the oral cavity.

Carcinosarcoma ex Non-Recurrent Pleomorphic Adenoma Composed of TTF-1 Positive Large Cell Neuroendocrine Carcinoma and Myofibrosarcoma: Apropos a Rare Case

We present a carcinosarcoma ex non-recurrent pleomorphic adenoma composed of a large cell neuroendocrine carcinomatous component and a spindle cell sarcoma with myofibroblastic differentiation. The tumor contained a hyalinized transition zone where the classical PA appeared to acquire two different histopathological patterns of malignant transformation of the epithelial component. The carcinomatous component was strongly and diffusely positive for low-molecular weight cytokeratins (AE1-3), synaptophysin, thyroid transcription factor-1 and focally positive for chromogranin A. All these markers were negative in the sarcomatous component. The sarcomatous component displayed immunoreactivity for smooth muscle actin with a predominantly linear, subplasmalemmal pattern. No expression of CD31, S100 protein, h-caldesmon, desmin, CD34, p63, myogenin, Myo D1 and c-kit was detected. Strong immunohistochemical expression of p53 was documented in both the carcinomatous and sarcomatous components as well as in the atypical epithelial component in the transition zone associated with the hyalinized pleomorphic adenoma.

Clinicopathological Characteristics and Outcome of Primary Sarcomatoid Carcinoma and Carcinosarcoma of the Liver

BackgroundPrimary sarcomatoid carcinoma (SC) and carcinosarcoma (CS) of the liver are rare tumors. Patients and MethodsFrom November 1999 to June 2011, clinicopathological features and outcome of 10 SC and 14 CS patients were retrospectively studied. ResultsIn the SC group, six patients had hepatocellular carcinoma and four had cholangiocellular carcinoma, while in the CS group, it was nine and five patients, respectively. All cases of the sarcomatous components were vimentin-positive. Pan-cytokeratin were stained in sarcomatous components of the SC group, but not in the CS group. The sarcomatous component in the SC group was negative for desmin, myoglobin, HHF35, SMA, CD68, Mac387, AAT, CD34, and S100. In the CS group, the sarcomatous components in six cases were malignant fibrous histiocytomas, six were fibrosarcomas, and two were rhabdomyosarcomas. Median survival times were 9.6 and 4.8 months for the SC and CS groups, respectively (P = 0.483). In univariate analysis, favorable predictors of overall survival were asymptomatic, Child–Pugh class A, no distant metastasis, and radical resection. ConclusionsSC and CS were highly aggressive malignancies with similar poor survival regardless of the histological and immunohistochemical findings. Early detection through regular physical examination and treatment with radical resection may improve the outcome of those patients.