Spindle Cell Elements Research Articles

Spindle Cell Lesions of the Breast: A Diagnostic Algorithm.

Spindle cell lesions of the breast represent a broad spectrum of entities, ranging from nonneoplastic reactive conditions to high-grade malignant tumors. The wide range makes breast spindle cell lesions a diagnostic pitfall. To review the classification of spindle cell lesions of the breast, including clinical features, morphologic characteristics, and the role of immunohistochemistry as well as molecular tools in assisting the differential diagnosis. A diagnostic algorithm will be proposed. Literature and personal experience are the sources for this study. Spindle cell lesions of the breast can be classified as biphasic or monophasic, with the former including both spindle cell and epithelial components, and the latter including only spindle cell elements. Each category is further subclassified as low or high grade. In the biphasic low-grade group, fibroadenoma and benign phyllodes tumor are the most common lesions. Other uncommon lesions include hamartoma, adenomyoepithelioma, and pseudoangiomatous stromal hyperplasia. In the biphasic high-grade group, borderline/malignant phyllodes tumor and biphasic metaplastic carcinoma are the main lesions to consider. In the monophasic low-grade group, reactive spindle cell nodule, nodular fasciitis, myofibroblastoma, fibromatosis, and fibromatosis-like metaplastic carcinoma have to be considered. In the monophasic high-grade group, the possible lesions are monophasic spindle cell metaplastic carcinoma, primary breast sarcoma, and metastases. Awareness of the clinical history and careful evaluation of any epithelial differentiation (with a large immunohistochemical panel) are crucial in the distinction.

Clinicopathological and immunohistochemical analysis of spindle cell carcinoma of the larynx or hypopharynx: A report of three cases.

Spindle cell carcinoma (SpCC) is a rare and unusual biphasic malignant tumor, which involves sarcomatoid proliferation of pleomorphic spindle cells and squamous cell carcinoma. There are various reports on the clinical and pathological findings of SpCC in the head and neck; however, this type of tumor remains uncommon in the larynx and hypopharynx. The histogenesis of SpCC has been the subject of debate for many decades. Although it is generally accepted that SpCC is a monoclonal epithelial neoplasm, and the spindle cell element is derived from squamous epithelium with divergent mesenchymal differentiation, this type of tumor poses a significant diagnostic challenge to pathologists and clinicians with regard to the therapeutic approach. In the present report, three cases of SpCC of the larynx or hypopharynx were investigated. The histological and immunohistochemistry findings are presented to provide further data on this rare type of tumor.

Analysis of metaplastic breast carcinoma: FNAC; histopathology and immunohistochemistry are complementary for diagnosis

Metaplastic breast carcinoma (MBC) is a rare malignancy comprised of ductal, squamous and/or mesenchymal elements with problematic diagnosis. This study analyses MBC identifying its cytologic and histologic features and emphasizing the combined role of FNAC, histopathology and immunohistochemistry (IHC) in its diagnosis. Cytology and histopathology files search yielded 21 cases identified as MBC from January 2005 to December 2010. FNAC and the histopathology slides were re-examined for the presence and frequency of various elements. Cytological and histopathological diagnoses were made and the cases subtyped according to WHO classification. Cytokeratin and vimenten IHC were used to confirm diagnosis when required. On FNAC, 52.4% were diagnosed as malignant, 9.5% as suspicious for malignancy and 38.1% as benign lesions. Most frequent cytologic findings were squamous and spindle cell elements (52.4% each). Histopathology revealed 76.2% pure epithelial tumors and 23.8% mixed epithelial-mesenchymal tumors. Squamous cell carcinoma was the most frequent histological subtype (33.3%). Carcinosarcomas were dimorphic on IHC& spindle cell carcinomas were positive for both cytokeratin and vimentin. Presence of dual components, squamous, spindle elements, mesenchymal fragments and necrosis in moderate to high cellularity breast FNAC provides clues for the diagnosis of MBC. FNAC; histopathology and IHC complement for diagnosis.

Abstract P1-01-22: The utility of axillary ultrasound and sentinel lymph node biopsy in the management of metaplastic breast carcinoma

Abstract Background: Metaplastic breast carcinoma (MBC) accounts for <5% of all breast malignancies. This entity represents a heterogenous group of tumors in which the adenocarcinomatous element is admixed with one or more neoplastic mesenchymal (spindle, squamous, chondroid, or osseous) elements. Patients typically present with large triple negative tumors and have a poor prognosis. The likelihood of lymph node (LN) involvement has been reported to be low in MBC patients. Due to the paucity of data, we undertook this study to explore the role of axillary ultrasound (US) and sentinel LN biopsy (SLNB) in the management of MBC. Methods: With IRB approval, we retrospectively identified patients diagnosed with MBC from 2001–2011 from the surgical pathology database. Histopathology and imaging were reviewed. Demographic, treatment and outcome data were obtained by clinical chart review. Data were analyzed using JMP 9.0 software. Results: We identified 41 women with MBC. Median age was 60 years (range 33–90). Histologic subtypes were spindle cell (46%), mixed adenocarcinoma and mesenchymal elements (20%), squamous cell (17%) chondroid/osseous (10%) and adenosquamous (7%). Tumor stage was T1 (24%), T2 (44%), T3 (12%) and T4 (20%). 26 patients (63%) were treated by mastectomy and 15 (37%) by wide excision. Of the 38 patients who underwent LN surgery (6 low-grade MBC, 32 intermediate/high-grade MBC), 10 (26%) were LN positive. All low-grade MBC patients were LN negative while 10 of 32 intermediate/high-grade MBC patients (31%) had LN metastasis. 22 patients had a preoperative axillary US. 14 patients had a negative axillary US and none had LN metastasis. 4 of 8 patients with suspicious axillary US findings had a preoperative axillary LN fine needle aspiration biopsy (FNAB) and 3 were positive for cancer. These patients proceeded directly to axillary LN dissection (ALND). 24 patients had a SLNB of whom one was SLN positive and underwent completion ALND. LN metastasis was associated with larger tumor size (p = 0.003), higher tumor grade (p = 0.04), angioinvasion (p = 0.07) and abnormal axillary US (p = 0.003). Surviving patients were followed for a mean (median) of 41 (30) months during which 13 (32%) recurred at a median of 6 months (IQR 3–17 months) and 11 (27%) subsequently died of disease. One SLN negative patient developed an axillary recurrence at 8 months, was successfully treated by ALND and is disease-free at 38 months. There were no axillary LN relapses after ALND. Conclusions: For clinically node-negative MBC patients, our contemporary data series suggests the incidence of occult LN metastasis is sufficiently high to warrant LN staging especially for patients with intermediate and high-grade tumors. This can be accomplished in a minimally invasive fashion with reasonable accuracy (∼97%) with axillary US, FNAB of sonographically suspicious LNs, and SLNB for patients with negative axillary US or FNAB. Axillary LND should be performed for patients with clinically and/or FNAB-positive LN for enhanced disease control. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-22.

Malignant pediatric brain tumor of primitive small round cell proliferation with bland-looking mesenchymal spindle cell elements

It is often difficult to classify rare malignant pediatric mixed brain tumors composed of mesenchymal elements. A 6-year-old boy presented to our hospital with a left frontal massive tumor manifesting as complaints of rapidly progressive right hemiparesis and motor aphasia over 2weeks. Computed tomography showed a left frontal mass with thick calcification. Magnetic resonance imaging revealed an enhanced lesion with perifocal edema and mass effect. Total removal of the tumor was performed. Histological examination of the resected tumor revealed an anaplastic malignant small round cell component with a bland-looking mesenchymal spindle cell component. The patient was treated with irradiation to the whole craniospinal axis and a boost to the tumor bed, followed by chemotherapy consisting of ifosfamide, cisplatin, and etoposide, resulting in good control without local recurrence or metastasis at 2years. A combined malignant tumor composed of ectodermal and mesenchymal components is generally named malignant ectomesenchymoma (MEM). The more malignant part of MEM is the mesenchymal component in most cases. In the present case, the more malignant component was not the mesenchymal component, but the small round cells.

Pathologic and molecular features of uterine carcinosarcomas

Uterine carcinosarcomas (UCSs), formerly known as malignant mixed müllerian tumors, are uncommon neoplasias that account for <5% of uterine malignancies. Traditionally, UCSs have been considered a subtype of sarcoma and the staging system and adjuvant oncological treatments used have been similar to those used for high-grade uterine sarcomas. However, there is now enough clinical, pathologic, and biological evidence to consider UCSs more closely related to high-grade endometrial carcinomas. Thus, these tumors should be staged based on the surgicopathologic staging system used for endometrial carcinomas. Morphologically, UCSs are heterogeneous biphasic tumors composed of an admixture of malignant (endometrioid and nonendometrioid) epithelial and (homologous and heterologous) mesenchymal elements in different proportions. UCSs predominantly metastasize as carcinomas and they are associated with a poor prognosis. Although stage is a consistent prognostic factor, the significance of several histopathological features, such as myometrial invasion, lymphovascular space involvement, type of carcinomatous component, extent of the sarcomatous component, and the presence of heterologous elements, remains controversial and probably differs among different stages. Although the diagnosis of UCS is not difficult in most cases, the differential diagnosis may include entities such as undifferentiated or dedifferentiated carcinoma, endometrioid adenocarcinoma with spindle cell elements, sarcomatous overgrowth in a low-grade müllerian adenosarcoma, and pure malignant mesenchymal tumors. Genetic and molecular studies have confirmed the clonal origin of most UCSs and have shown these tumors to be similar to those observed in high-grade/nonendometrioid carcinomas, with p53 mutations being the most common molecular alteration. Finally, from a biological standpoint, the process by which epithelial malignant cells of UCS transdifferentiate to malignant mesenchymal cells could be considered a true example of epithelial mesenchymal transition in human neoplasias.

Clinicopathologic study of 53 metaplastic breast carcinomas: their elements and prognostic implications

Metaplastic carcinoma of the breast is a relatively rare cancer and includes various histologic types. In this cancer, metaplastic elements are heterogeneous and sometimes mixed. We investigated, by histopathologic means, these elements and clinical implications that could indicate the clinical course (including the prognosis). Fifty-three metaplastic breast carcinoma cases and their prognoses were investigated by initially examining the presence or absence of spindle-cell elements, and then the presence or absence of other elements. Spindle cells were classified as high or low grade. The number of spindle-cell-positive cases was 24 (45%) of 53. The 24 spindle-cell (+) cases were subdivided into 12 high-grade (HGsp) (distant metastatic rate per 100 person-years, 13.27) and 12 low-grade (LGsp) (0.00) patients. Spindle-cell (-) cases were subdivided into 22 pure squamous cell carcinomas (5.93) and 7 matrix-producing carcinomas (0.00). There were significant differences among the 4 groups with regard to the disease-free period (P = .0081, log-rank test). The distant metastatic risks in the HGsp and pure squamous cell carcinomas groups were significantly higher than that in the matrix-producing carcinoma + LGsp group (nonmetastatic groups) after controlling for the effects of tumor size and lymph node metastasis (P = .019 and P = .016, respectively, Poisson regression model). The presence of high-grade spindle cells was related to the prognosis, and some histologic subtypes may be important with respect to the prognosis. The presence of high-grade spindle cells in metaplastic breast carcinoma may indicate aggressive behavior.

Sarcomatoid squamous cell carcinoma of uterine cervix

Sarcomatoid squamous cell carcinoma (SSCC) is composed of squamous cell carcinoma element and spindle cell element, and can occur in any organ, such as the lung, skin and esophagus. But SSCC in uterine cervix is very rare. The prognosis of SSCC is poorer than squamous cell carcinoma (SCC) of uterine cervix. We report here a case of SSCC of uterine cervix with a brief review of literature.

Spindle-Cell Hibernoma: A Clinicopathologic Comparison of This New Variant

Spindle-cell hibernoma is 1 of 4 histologic variants of hibernomas, which are rare lipomatous tumors distinguished from other lipomas by their brown fat component. This article presents a case of a spindle-cell hibernoma that developed in the groin of a 58-year-old man, and is 1 of only 5 known cases of spindle-cell hibernoma published in the scientific literature. Minimal information is available regarding the clinicopathologic characteristics of the 4 hibernoma variants: typical, lipoma-like, myxoid, and spindle-cell. Spindle-cell hibernoma is believed to be the rarest variant, accounting for approximately 2% of hibernomas. The spindle-cell variant predominantly develops in the fourth and fifth decades, with an average age at diagnosis of 42.5 years (range, 28-59 years). It has a male predilection of 4:1. Previously reported only in the posterior neck and scalp, the groin is now added to the sites of spindle-cell hibernoma occurrence. Our patient's tumor demonstrated low-attenuation on computed tomography and contained moderately-attenuating internal septae. Histologically, in addition to the multivacuolated brown fat component common to all hibernomas, spindle-cell hibernoma has a spindle-cell element without vacuolization that is CD34 positive. No prior treatment details are available on this particular variant. Our patient was treated by marginal excision and was disease free through 13 months of follow-up.

Mucinous Tubular and Spindle Cell Carcinoma of the Kidney With Sarcomatoid Change

Sarcomatoid change has been well documented in the various subtypes of renal cell carcinoma (RCC) and its presence is known to portend a worse prognosis in RCC. Mucinous tubular and spindle cell carcinoma is a RCC subtype, which is defined as polymorphous histology wherein the spindled epithelial cell is an inherent carcinomatous component. Many of these putatively low-grade tumors have been previously misdiagnosed as unclassified or sarcomatoid papillary RCC. We present 2 examples of hitherto undescribed sarcomatoid change in mucinous tubular and spindle cell carcinoma in a 71-year-old woman and an 80-year-old man who both underwent a radical nephrectomy procedure. In addition to the classic mucinous tubular and spindle cell carcinoma morphology, both cases had a sarcomatoid component characterized by predominantly high-grade spindle cells, solid pleomorphic epithelioid cells, and malignant fibrous histiocytoma-like storiform patterns. Sarcomatoid change comprised 60% and 20% of the tumors, respectively. Unlike the spindle sarcomatoid cells, the inherent spindle cell elements of mucinous tubular and spindle cell carcinoma had distinctively low-grade cytology and occasionally blended with tubular structures and variable mucinous stroma. The sarcomatoid cells were associated with significant necrosis, marked nuclear pleomorphism, mitoses of up to 5/10 high power field, higher proliferation fraction (MIB1), and loss of alpha-methylacyl-CoA racemase or cytokeratin 7 expression. Cytogenetic analysis in 1 tumor showed loss of chromosomes 14 and 15 and gains of chromosomes 2, 5, 7, 9, 10, 12, 17, 19, 20, 22, and X. Widespread metastasis to lymph nodes, bones and lungs occurred in one patient who succumbed 9 months after nephrectomy. Helpful features in distinguishing spindle cells of sarcomatoid component versus that of the native tumor include the presence of high-grade cytology, expansile growth with loss of typical imperceptible blending with the tubulo-papillary component, extensive necrosis, high mitotic activity, high proliferation fraction, and loss of expression of alpha-methylacyl-CoA racemase that contrasted the classic areas. Distinction of the sarcomatoid histology from inherent spindle cell component of mucinous tubular and spindle cell carcinoma is important because of its unfavorable prognostic implication.

Carcinosarcoma of the penis

Carcinosarcoma of the penis is extremely rare and little is known about its biological behaviour. We report the second such case and discuss its histological categorisation and biological behaviour. A total penectomy with perineal urethrostomy was performed without lymphadenectomy in an 83-year old presenting with a fungating penile mass. Microscopy of the gross specimen showed a biphasic tumour with both squamous and spindle cell elements. Immunohistochemical staining for epithelial markers showed positivity in the squamous cell elements but was uniformly negative in the spindle component. Immunohistochemistry of the spindle cell element demonstrated mesenchymal markers. The patient refused further treatment and follow up but presented at 26 months with inguinal lymphadenopathy. Biopsy confirmed squamous cell carcinoma metastasis consistent with penile origin. The patient refused further surgery and received pelvic irradiation. He died 6 months later. This case illustrates the biological behaviour of this rare tumour.

Monophasic epithelial synovial sarcoma arising in the temporomandibular joint

Synovial sarcoma is a mesenchymal spindle-cell tumour that occurs infrequently in the head and neck. It originates from unknown stem cells differentiating into mesenchymal and/or epithelial structures. Most synovial sarcomas are biphasic in character, consisting of epithelial and spindle-cell elements . Here is reported a case of monophasic epithelial synovial sarcoma arising in the temporomandibular joint. The tumour was of a predominantly epithelial pattern, although a minute area of sarcomatous cells was found. The primary mode of treatment was wide en-bloc excision. Two years after surgery, the patient died of hepatocelluar carcinoma, but there was no evidence of synovial sarcoma recurrence.

Polypoid Spindle Cell Carcinoma of the Esophagus

Rare histologic variants of esophageal cancer account for about 5% of cases. As its name suggests, polypoid spindle cell carcinoma of the esophagus (carcinosarcoma, pseudosarcoma) is comprised of both epithelial and spindle cell elements. The nomenclature reflects both the historical controversy over the lesion's cell of origin as well as its characteristic fungating intraluminal growth pattern. The authors report a case of polypoid spindle cell carcinoma of the esophagus that was preoperatively diagnosed as a visceral sarcoma.

膀胱肉腫様癌の1例

A 49-year-old female visited to our department with complaints of gross hematuria and micturition pain. Cystoscopic examination revealed a 5-cm diameter solid broad-based tumor located at the front wall of the bladder. Histologically, the tumor was composed of grade 2 urothelial carcinoma (UC) element and sarcomatous spindle cell element. Immunohistochemical examination demonstrated that both UC and spindle cells were positive for cytokeratin. In addition, spindle cells did not stain for S-100 protein or smooth muscle actin. We diagnosed the tumor as sarcomatoid carcinoma and performed total cystectomy and ileal conduit without chemotherapy and radiation. The patient has remained without any evidence of recurrence for 14 months after operation. Sarcomatoid carcinoma of the bladder has aggressive malignant potential and poor prognosis. An appropriate adjuvant therapy for sarcomatoid carcinoma with metastasis has not been established. Total cystectomy is recommended as soon as possible after pathological diagnosis in the same manner as conventional high grade UC.

Personal Experience in Surgical Management of Pulmonary Pleomorphic Carcinoma

Background Pleomorphic carcinoma is a rare epithelial malignant tumor. Pulmonary pleomorphic carcinoma was introduced by the 1999 World Health Organization classification as a new peculiar type of lung carcinoma showing concurrent malignant epithelial and sarcomatoid spindle cell elements. Few reports describe its clinical behavior. My colleagues and I report a series of patients surgically treated for pulmonary pleomorphic carcinoma to describe our experience with this malignant neoplasm. Methods Twenty cases of pleomorphic pulmonary carcinoma were collected and studied clinicopathologically. All patients underwent surgical resection. The cases were as follows: 6 stage I, 12 stage II, and 2 stage IIIA. Histologic diagnosis was established by using light microscopic examination and immunohistochemistry. Survival rates were calculated with the Kaplan-Meier method. Results We postoperatively diagnosed 20 cases of pleomorphic carcinoma: 14 cases were exclusively spindle and giant-cell carcinomas, 2 cases were spindle and giant-cell carcinoma combined with adenocarcinoma, 2 were combined with squamous cell carcinoma, and 2 were combined with large cell carcinoma. At last follow-up, 4 patients were still alive; they were postoperative T1 N0 and T2 N0. The remaining 16 patients died from early distant metastases. The median duration of disease-free survival was 5 months. The median duration of overall survival was 8 months. Conclusions The prognosis of patients with pleomorphic carcinoma was poor, despite surgery and adjuvant chemotherapy, because of early relapse of disease. Nodal involvement was a determinant prognostic variable, because advanced stages were related to worse prognosis. In case of preoperatively proven pulmonary pleomorphic carcinoma, surgery should be recommended to N0 patients.

Ectopic Hamartomatous Thymoma: A Case Report Showing CD99+ Lymphocytes and a Low Proliferation Index

Ectopic hamartomatous thymoma is a rare benign tumor that consists of spindle, epithelial, and adipose cell elements. We present a case of this lesion arising in the supraclavicular region of a 59-year-old man, including the characteristic immunohistochemical and ultrastructural findings. DNA flow cytometry revealed diploidy with a low proliferation index (6.73%). The tumor contained CD99+ lymphocytes; CD99 (MIC2) can serve as a useful marker of immature T cells. These findings suggest that ectopic hamartomatous thymoma may develop from the third branchial pouch or thymic anlage.

Sarcoma sinovial primário da orofaringe: relato de caso

O sarcoma sinovial primário da cabeça e pescoço é um tumor raro. Em torno de 90 casos foram descritos na literatura. Relatamos um caso adicional ocorrido em um paciente jovem do sexo masculino comprometendo a orofaringe. O tumor apresentou típico crescimento bifásico, fibrossarcomatoso e epitelial, com estruturas pseudo-glandulares. O diagnóstico final foi obtido pelo exame da peça cirúrgica com preparações histológicas de rotina e análise imunohistoquímica.

MR Imaging Findings of Gliosarcoma: Report of Three Cases

Gliosarcoma is a rare primary brain tumor composed of neoplastic glial cells and a sareomatous spindle-cell element. We report three cases of gliosarcoma, and describe their MR findings, which in many respects are very similar to those of malignant astrocytomas. Gliosarcomas are, however, more peripherally located, abutting and/or invading the dura mater, and at T2-weighted imaging their signal intensity is lower than is usually the case with malignant astrocyomas. Despite its rarity, the possibility of gliosarcoma should be considered when MR findings of this nature are apparent.

CD44 isoform expression in synovial sarcoma correlates with epitheliogenesis but not prognosis.

We immunohistochemically determined the expression of CD44 standard and splice variant isoforms in a series of synovial sarcomas and sought correlations with histological subtype and clinical parameters including outcome. From 39 patients, a total of 56 formalin-fixed and paraffin-embedded tumour samples (including initial, recurrent and metastatic tumours) were used to immunohistochemically evaluate the expression of epitopes encoded by CD44s and the CD44 splice variants CD44v3-v10. Significance of proposed prognostic indicators was evaluated in relation to the survival, time to local recurrence and time to metastases using log-rank analysis. Sixty-four percent of synovial sarcomas expressed CD44s and 46% expressed CD44v3-v10 (var). Synovial sarcomas with epithelial or epithelioid areas preferentially expressed CD44s in these areas when compared with the spindle cell element. There were no correlations with clinical parameters or outcome. The expression of CD44 was not found to correlate with survival, local recurrence or metastatic ability. In synovial sarcoma, CD44 and variant isoform expression appears to be associated with the degree of epithelial differentiation. CD44 expression in synovial sarcoma shows interesting similarities to CD44 expression in embryological epitheliogenesis.

Ectopic hamartomatous thymoma: a case study and review of the literature

Ectopic hamartomatous thymoma is a rare and distinctive tumor found in the deep soft tissues of the neck, which is characterized histopathologically by a mixture of spindle, epithelial, and adipose cell elements. We present a case of this lesion occurring in a 39-year-old male. The characteristic histochemical and immunohistochemical findings of these tumors are demonstrated. In addition, review of the reported histological, immunohistochemical and ultrastructural findings is presented together with a table of clinical findings in the tumors so far described. A brief discussion of theories of histogenesis and possible differential diagnosis is included.