Primitive Spindle Cells Research Articles

DICER1 Syndrome in a 25-Year-Old Female: Autopsy Case Report of Mixed Sex Cord-Stromal and Primitive Sarcoma Tumors with Diverse Differentiation Patterns

Abstract Introduction/Objective DICER-1 syndrome is a rare disorder characterized by germline mutations in the DICER1 gene, known to confer a lifetime risk of developing a variety of benign and malignant pathologies. This syndrome typically affects young individuals, though it exhibits exceedingly variable and relatively low penetrance of the neoplastic manifestations. Methods/Case Report We report on a 25-year-old woman with a history of metastatic DICER-1 related mixed pattern sex-cord stromal tumor of the ovary and primitive sarcoma of the liver. Her treatment involved extensive surgeries, including oophorectomy, salpingectomy, and partial hepatectomy, and multiple cycles of chemotherapy. Antemortem surgical pathological analyses revealed a poorly differentiated, primitive sarcoma in the liver and a sex cord-stromal tumor with Sertoli-Leydig and juvenile granulosa cell tumor-like features. The liver tumor exhibited a primitive spindle cell sarcoma with anaplastic features as well as chondrosarcomatous and rhabdomyosarcomatous patterns, suggesting a primary DICER1-related sarcoma. Immunohistochemistry confirmed the tumor’s complex multilineage differentiation, showing variable positivity for CD99, vimentin, CD10, BCL2, and Glypican-3. Positivity for Desmin and MyoD1 was focal, while the tumor was negative for inhibin, calretinin, AE1/3, AFP, and beta-catenin, overall supporting a DICER1-associated sarcoma diagnosis. She eventually died from terminal cardiac arrest secondary to complications from her metastatic cancer. An autopsy revealed a significant abdominopelvic mass leading to hemoperitoneum and extensive organ involvement, highlighting the aggressive nature of DICER1-associated malignancies. Results (if a Case Study enter NA) NA Conclusion This case underscores the importance of recognizing the broad manifestations of DICER-1 syndrome for accurate diagnosis, genetic counseling, and tailored management. Highlighting tumor morphology and immunohistochemical features enriches our understanding of DICER-1 pathology, advancing diagnosis and treatment prospects for affected individuals.

Cervical Pleuropulmonary Blastoma-like Tumor Associated With DICER1 and TP53 Mutations.

We describe a very unusual cervical tumor in a 12-yr-old patient with a clinical history indicative of DICER1 syndrome. Morphologic, immunohistochemical, and molecular genetic analysis together helped to diagnose this lesion as a cervical pleuropulmonary blastoma-like tumor, associated with TP53 and DICER1 mutations. The tumor displayed usual histologic features including mixtures of embryonal rhabdomyosarcoma, sarcomatous cartilage, compact blastema, primitive spindle cells and anaplasia, akin to type III pleuropulmonary blastoma, and trabecular and retiform patterns. In addition to expanding the phenotypic spectrum of DICER1 -associated conditions, we draw attention to genotype-phenotype correlations in DICER1 -associated tumors, particularly as they relate to the discovery of a heritable tumor predisposition syndrome.

Pediatric Non-Myofibroblastic Primitive Spindle Cell Tumors with ALK Gene Rearrangements and Response to Crizotinib.

We describe two poorly differentiated, non-myofibroblastic (SMA-, S100+, CD34±), spindle cell neoplasms with immunohistochemical positivity for ALK and with ALK gene rearrangements leading to PLEKHH2::ALK and CLTC::ALK fusions, respectively. ALK protein overexpression and/or gene fusions should be evaluated in poorly differentiated spindle cell neoplasms, even when there is an absence of a myofibroblastic phenotype. A positive ALK evaluation has therapeutic implications as both tumors responded to single-agent treatment with the tyrosine kinase inhibitor crizotinib.

An abdominal extraskeletal osteosarcoma: A case report

Primary abdominal extraskeletal osteosarcoma (EOS) is a rare carcinoma. The present study reports a case of a primary abdominal EOS involving the greater omentum and also presents a review of the literature on the etiology, diagnosis, differential diagnosis, pathological features, treatment and prognosis of the disease. The patient in the present study underwent laparoscopic surgery. A pathological examination revealed that the tumor tissues contained malignant and primitive spindle cells with varying amounts of neoplastic osteoid and osseous or cartilaginous tissue. The post-operative follow-up appointments were scheduled at three-month intervals for two years. The tumor recurred three months after the surgery.

Adult hepatoblastoma: Learning from children

Hepatoblastoma is the most common malignant liver tumour in infants and young children. Its occurrence in the adult population is debated and has been questioned. The aim of this paper is to review the histological and clinical features of adult hepatoblastoma as described in the adult literature, and to compare the findings with those of paediatric hepatoblastoma. The developmental and molecular aspects of hepatoblastoma are reviewed and their potential contribution to diagnosis of adult hepatoblastoma discussed. Case reports of adult hepatoblastoma identified by a PubMed search of the English, French, German, Italian, and Spanish literature through March 2011 were reviewed. Forty-five cases of hepatoblastoma were collected. Age at presentation was variable. Survival was uniformly poor, except for the rare patients who presented with the relatively differentiated, foetal type. The common denominator between adult and paediatric cases is the occurrence of embryonal or immature aspect of the tumours. Whether the adult cases of hepatoblastoma represent blastemal tumours, stem cell tumours, or unusual differentiation patterns in otherwise more frequent adult liver tumours remains to be established. Adult tumours labelled as hepatoblastoma are characterised by malignant appearing mesenchymal components. Surgical management is the cornerstone of therapy in children and also appears to confer an improved prognosis in adults. Whether adult hepatoblastoma exists, remains controversial. Indeed, several features described in adult cases are markedly different from hepatoblastoma as it is understood in children, and other differential diagnoses should also be entertained. Nonetheless, hepatoblastoma should be considered in adults presenting with primary liver tumours in the absence of pre-existing liver disease. Adult and paediatric patients with immature hepatoblastoma appear to have worse outcomes, and adults presenting with presumed hepatoblastoma have an overall poorer prognosis than children with hepatoblastoma. In all patients, surgery should be the treatment of choice, neoadjuvant chemotherapy is advisable.

A Case of Tumor-induced Osteomalacia with Elevated Fibroblast Growth Factor-23

Tumor-induced osteomalacia (TIO), a paraneoplastic disease, is characterized by hypophosphatemia, and caused by renal phosphate wasting inappropriately, normal or decreased 1, 25(OH)2D3 production, and defective calcification of cartilage and bone. Because the removal of the responsible tumor normalizes phosphate metabolism, unidentified humoral phosphaturic factors (phosphatonin) are believed to be responsible for this syndrome. These factors include fibroblast growth factor (FGF)-23, secreted frizzled-related protein-4 and matrix extracellular phosphoglycoprotein. However, no case of TIO producing FGF-23 has been clearly reported in Korea. Herein, a case of TIO producing FGF-23 in a 45-year-old woman is reported. The patient presented with a large tumor on her buttock, with severe bone and muscle pain. A histological examination of the tumor revealed a mixed connective tissue tumor, consisting of deposition of calcified materials and surrounding primitive spindle cells, with prominent vascularity. Whether FGF-23 is a secreted factor, as well as its levels of expression in tumors were investigated. An immunohistochemical study showed the tumor cells to be FGF-23 positive. Furthermore, the levels of serum FGF-23 were extremely high and an RT-PCR analysis, using total RNA from the tumor, revealed the abundant expression of FGF-23 mRNA. After removal of the tumor, all the biochemical and hormonal abnormalities disappeared, with marked symptomatic improvement. (J Kor Endocrine Soc 22:142~148, 2007)

Hepatobiliary cystadenoma with mesenchymal stroma in a patient with chronic hepatitis C

Hepatobiliary cystadenoma was suggested to be uncommon and it is often difficult to make a differential diagnosis. We report a case of a 65-year-old woman who presented with changes in the structure of a cyst that had been observed for the previous 10 years. Diagnostic imaging revealed a 7-cm-diameter cystic lesion with internal septations and papillary projections in her liver. All laboratory test results were normal; however, cystic fluid carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were raised, at 160 ng/ml andover 200,000 U/ml, respectively. Owing to changes in the structure of the cyst and the difficulty of differential diagnosis from cystadenocarcinoma, a complete surgical excision was performed. The histological findings indicated that the tumor consisted of a multilocular cyst lined by glandular cells (with cuboidal or tall columnar cystoplasm), which were immunohistochemically positive for cytokeratin, CEA, epithelial membrane antigen, and CA 19-9. The underlying stroma was composed of proliferating primitive spindle cells which were immunoreactive for vimentin, alpha-smooth muscle actin, muscle-specific actin, and desmin, and resembled ovarian stroma. From these findings, this tumor was diagnosed as hepatobiliary cystadenoma with mesenchymal stroma. Even though the tumor was previously diagnosed as a simple liver cyst, it was necessary to pay special attention to the changes in the structure of the cyst, using ultra sonography and/or computed tomography, bearing in mind hepatobiliary cystadenoma with mesenchymal stroma. The malignant potential of this tumor is stressed, and complete surgical resection is the recommended therapy.

An Ultrastructural, Immunohistochemical, and Cytogenetical Study of a Monophasic Pulmonary Synovial Sarcoma: Implications of the Frequent Ultrastructure of Oligocilia and Concentric Membranous Bodies with Positive Immunostaining for VS38c and MEF2

A rare case of a monophasic pulmonary synovial sarcoma is reported. A 44-year-old Japanese man underwent lower lobectomy for a nodular mass in his right lung. Immunohistochemical study of the excised primitive spindle cell sarcoma revealed occasional positive stains by hitherto reported antigens of S-100, cytokeratin 7, high molecular weight cytokeratin (34betaE12), pankeratin (AE1/AE3), and EMA, which were helpful for the differential diagnosis of other spindle cell sarcomas. Furthermore, positive immunostains for MEF2, VS38c (plasma cell antigen), and bcl-2 were rather significant findings in the present case. The definitive evidence that molecular genetic analysis showed a clonal single electrophoretic band of SYT-SSX mutated chimera gene was conclusive for the pathological diagnosis. The implications of the frequently seen ultrastructure of oligocilia and concentric membranous bodies with positive stains for VS38c and MEF2 are discussed. In the difficult pathological diagnosis of a rare and undifferentiated type of sarcoma with unusual clinicopathological features generated at an unusual site, comprehensive ultrastructural, immunohistochemical, and cytogenetic studies will lead to the correct pathological diagnosis and elucidate the detailed characteristics of the tumor.

Intradermal spindle cell/pleomorphic lipoma: a distinct subset.

Spindle cell/pleomorphic lipomas are a group of benign lipogenic tumors composed of primitive spindle cells, multinucleated giant cells, and mature adipocytes. These tumors have rarely been reported to arise in the dermis and may be misdiagnosed in this location. Twenty (12.7%) intradermal lesions identified among 157 spindle cell/pleomorphic lipomas in the authors' files were studied clinicopathologically and immunohistochemically. The patients' ages ranged from 20 to 85 years (median: 42 years); 14 of 20 patients were female (70%). Anatomical sites were the head/neck region (7 cases, 4 of which arose on the face), shoulder/upper back (4 cases), lower limbs (4 cases), trunk (3 cases), and upper limbs (2 cases). Most lesions presented as a soft and slowly enlarging cutaneous nodule, usually measuring less than 2.5 cm. Histologically, these dermal lesions differed from usual spindle cell/pleomorphic lipoma, being unencapsulated with poorly defined infiltrative margins, although the cytomorphologic findings, ropy collagen, and mast cells were as seen in usual subcutaneous lesions. Six cases showed features of pleomorphic lipoma. Immunohistochemically, lesional cells stained positively for CD34 and were negative for S-100 protein. One case recurred locally after 21 years. Dermal spindle cell/pleomorphic lipomas are distinctive in their apparent female predilection, wider anatomical distribution than subcutaneous lesions, and lack of circumscription. These unusual features can cause problems in differential diagnosis.

Oncogenic Osteomalacia Caused by a Phosphaturic Mesenchymal Tumor of the Oral Cavity

We report a case of oncogenic osteomalacia associated with a phosphaturic mesenchymal tumor in a 31-year-old woman. She was presented with severe generalized bone and muscle pain and was restricted to bed. She lost 20cm in height over the 8 years since she had first noticed a pain in her thigh. A walnut-sized, hard, soft tissue tumor was found very easily beside her lower molar teeth. Radiologic examination revealed a remarkable decrease in bone density and multiple pathologic fractures of spine, femur and phalangeal bones. Severe hypophosphatemia, hyperphosphaturia, low plasma 1,25-dihydroxyvitamin D3 level and high plasma PTH level were disclosed at presentation. Histomorphometric examination revealed an extensive area of unmineralized osteoid and little mineralizing activity. A pharmacologic dose of 1α-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 slightly increased the serum phosphate level and renal tubular reabsorption of phosphate, and slightly decreased plasma PTH level without any symptomatic improvement. Histologic examination of the tumor revealed a mixed connective tissue tumor that consisted of central woveh bones and surrounding primitive spindle cells with prominent vascularities. After removal of the tumor, all biochemical, hormonal and radiologic abnormalities disappeared with remarkable symptomatic improvement.

An immunohistological study of steroid localization in sertoli-leydig tumors of the ovary and testis

Nine ovarian Sertoli-Leydig tumors, showing varying degrees of differentiation, one pure ovarian Sertoli cell tumor, and one poorly differentiated stromal tumor of the testis, were examined for the presence of testosterone, estradiol and progesterone with an indirect immunoperoxidase method on formalin fixed paraffin embedded tissue. Clinically all nine patients with Sertoli-Leydig tumors had evidence of increased androgen production, manifested by either hirsutism or virilization; elevated serum testosterone was found in all four patients in whom it was measured. The patients with the pure ovarian Sertoli cell and testicular tumors were asymptomatic except for the presence of a mass. Testosterone was identified in Leydig cells in nine instances, in Sertoli cells in six, and in poorly differentiated spindle cells resembling the mesenchyme of the embryonic gonad in two. Cells with vacuolated cytoplasm, both Sertoli and Leydig cells, though positive for lipid were consistently negative for testosterone. Estradiol was present in Leydig cells in nine instances, in Sertoli cells in five, and in primitive gonadal stomal cells in two. The pattern of distribution was similar to that of testosterone but the intensity of the reaction for estradiol was generally less than that for testosterone. Progesterone was identified in Sertoli cells in one instance and was weakly positive in Leydig cells in three instances. The presence of testosterone and estradiol in both Sertoli and Leydig cells as well as in primitive spindle cells resembling those found in the embryonic gonad suggests that the latter cell is the precursor for both Sertoli and Leydig cells.

家鶏卵黄嚢造血に関する研究

By performing tissue culture of chick blastoderm and observing the spindle cells at the embryonic stage under a phase-contrast microscope, the author obtained the following results.In the present observation the author recognized the cohesive cells that resembled primitive erythroblasts in the stage of 20 to 30 somites as observable by the stained specimen but had different pseudopodial and cell body movements in living conditions and possessing no hemoglobin, namely, a group of primitive spindle cell blasts. In culture these cells first project flat tongue-like pseudopodia aud then go into flagellar movement and then with elongation of mitochondria, they are differentiated to spindle cell blasts. And finally, their cell body growing flatter and flatter, they are differentiated into spindle cells that move as if the cell is flowing loosely out of the edge, flattering a portion of the prejection like a flag, or moving in a line.As for the differentiation of spindle cells in the hematopoiesis of chick embryo at the embryonic stage, it has been conclueded that spindle cells are not differentiated from primitive erythroblasts, but the differentiation takes the course from primitive spindle cell blasts to spindle cell blasts and then to apindle cells.