Atypical Spindle Research Articles

2730 Unexpected Cause of Globus Pharyngeous: Gastric Leiomyosarcoma

INTRODUCTION: Soft tissue sarcomas (STS) are derived from smooth muscle cells and typically arise in adipose tissue, blood vessels or structural tissue surrounding the organs of the body. One of the most common types of STS is leiomyosarcoma (LMS) which account for 11% of all sarcomas diagnosed. Gastric LMS are exceptionally rare and make up 0.1% of all mesenchymal tumors of the stomach. CASE DESCRIPTION/METHODS: A 72 year-old male presented to the gastroenterology clinic with complains of globus pharyngeus, migrating abdominal discomfort and a 4-month 18 pound weight loss. Endoscopy revealed a large bloody friable mass in the posterior wall of the stomach. Biopsy demonstrated atypical spindle cell proliferation. Immunohistochemistry was positive for Smooth Muscle Actin (SMA), desmin and CD34; cKIT and DOG1 was negative. He was diagnosed with high grade LMS of the stomach with no metastasis after unremarkable positron emission tomography scan. The patient underwent total gastrectomy with splenectomy en-bloc resection to achieve wide negative margins. DISCUSSION: This case highlights an unexpected cause of globus pahryngeus: Gastric LMS which is important to differentiate from gastrointestinal stromal tumor (GIST) as its management and prognosis differ. LMS represent 0.1% of all gastric tumors, and 3% of all gastrointestinal malignancies. In contrast, GIST has annual incidence of 11-14.5 per million population. LMS and GIST appear similar on gross assessment and clinical symptoms and need to be differentiated via immunohistochemical staining. LMS are actin and desmin reactive with DOG1.1 typically being absent. Further, LMS lack cKIT and PDGFRα mutations that are seen in GIST. Management of GIST with tyrosine kinase is potentially lifesaving, whereas no such treatment exists for LMS where the cornerstone of treatment is surgery. Chemotherapy and radiation have been shown to be only helpful for palliative measures. They are intrinsically aggressive tumors and 90% are moderate to high grade at time of diagnosis with evidence of metastatic disease. We are far from understanding the pathology of LMS and its risk factors. This case confirms our present understanding of LMS; as shown by positive markers as well a diagnosis of high grade tumor on presentation. However, it also challenges our current understanding of LMS in its unusual symptomatology and lack of metastatic disease. Due to its low incidence, it is crucial to report cases such as this in order to further our understanding of the tumor.

1925 GIST Kidding: Primary Gastric Synovial Sarcoma Presenting as Hematemesis

INTRODUCTION: Synovial sarcoma (SS) is an uncommon subtype of mesenchymal derived solid tumors that is characterized by its unique histologic pattern. It is most often found in the extremities and rarely, the digestive tract, which can lead to gastrointestinal bleeding. Gastric tumors of mesenchymal origin often have overlapping radiographic and endoscopic appearances, which presents a significant challenge in diagnosis. We report one of only 3 confirmed cases of primary gastric synovial sarcoma of the lesser curvature in a patient who presented with hematemesis. CASE DESCRIPTION/METHODS: A 26-year-old male presented with a two-week history of worsening abdominal pain and intermittent hematemesis. He denied any history of hematochezia, melena, early satiety, weight loss, recent NSAID use or alcohol ingestion. Exam was notable for epigastric tenderness without rebound or guarding. Labs revealed microcytic anemia and thrombocytopenia without transaminitis or elevated lipase. Abdominal CT showed an 8 cm mass along the posterior gastric body with suspicion for intratumoral hemorrhage, highly suggestive of a gastrointestinal stromal tumor (GIST) [Figure 1]. EGD revealed a large, ulcerated, non-bleeding, non-circumferential, submucosal mass on the lesser curvature of the stomach, also concerning for a GIST [Figure 2]. Endoscopic ultrasound showed neither hepatic invasion nor lymphadenopathy. Partial gastrectomy pathology supported the endoscopic biopsy results, which showed high grade, monophasic, atypical spindle cells with t(X;18)(SYT-SSX) chromosomal translocation by fluorescence in situ hybridization (FISH). Immunohistochemistry (IHC) was strongly positive for TLE1 staining, but negative for C-KIT and DOG-1, to which GISTs are immunoreactive, confirming a diagnosis of primary gastric synovial sarcoma [Figure 3]. He tolerated 6 cycles of sarcoma-directed chemotherapy without evidence of progressive disease. DISCUSSION: Intramural gastric spindle cell malignancies are difficult to distinguish from one another, and require different disease-tailored therapies. Though GISTs account for 90% of these tumors, other rare pathologies exist. These include synovial sarcomas, which are characterized by a variable degree of epithelial differentiation associated with a disease-specific gene translocation. In patients with hematemesis found to have endoscopic and radiographic findings suspicious for GIST, ICH and FISH analyses are crucial to differentiate between mesenchymal malignancies to guide effective therapy.

Primary Smooth Muscle Tumor of Breast: An Unusual Case Presentation

Abstract Introduction Primary smooth muscle tumors (SMT) of the breast are rare with leiomyosarcomas representing less than 0.1% of all malignant breast tumors. Case Presentation A 58-year-old female with no significant past medical history noted on screening mammography to have a circumscribed 6-mm nodule in the right breast, upper outer quadrant. Core needle biopsy showed a spindle cell neoplasm with smooth muscle differentiation. The excisional biopsy showed a 6-mm lesion composed of atypical hyperchromatic spindle cells in fascicles, marked nuclear pleomorphism, and 5 mitoses per 10 high-power fields. By immunohistochemistry, the spindle cells were positive for smooth muscle actin, desmin, and negative for S-100 and cytokeratin AE1/AE3. Positron emission tomography/computed tomography of head/neck, chest, abdomen, and pelvis did not identify other neoplasms. Despite the lesion size, findings were supportive of a leiomyosarcoma. Discussion Breast SMTs have nonspecific clinical or imaging features. Histologically, these present as spindle cell tumors with smooth muscle differentiation. Initial workup starts with distinction between benign and malignant neoplasms. The malignant SMTs are usually large tumors with cytologic atypia and mitotic activity used as diagnostic criteria. In addition, the distinction between primary and metastasis is important and frequently relies on clinical history and exclusion of other primary origins by radiographic survey. In the current case, although the tumor size is unusually small, the histological features and absence of other primary malignancies support the diagnosis of a leiomyosarcoma. Conclusion Primary leiomyosarcoma of breast is extremely uncommon with less than 70 cases reported in the literature. Although they are usually large tumors, this diagnosis should be included in the differential diagnosis when smooth muscle differentiation, significant atypia, and mitoses are encountered in a spindle cell tumor of the breast.

Primary Chondroblastic Osteosarcoma of the Breast in a Teenager: What Is Changing?

Abstract Background Nonepithelial tumors of the breast are extremely rare and have an incidence of less than 1%. The most common nonepithelial breast tumor is phyllodes tumor (PT), which accounts for 61%. Primary osteosarcomas of the breast contribute up to only 12.5% of all the extraosseous osteosarcomas, and among young females, they are extremely rare, especially in those without a previous history of primary bone osteosarcoma. A case of a 16-year-old female with primary chondroblastic osteosarcoma of the left breast is herein presented. Case Description In this report, we describe and report a 16-year-old female with neither a previous history of bone osteosarcoma nor a family history of breast cancer who was diagnosed with a primary chondroblastic osteosarcoma of the left breast. The mass was shining, warm, firm, and slightly fixed. The excisional biopsy showed a large tumor measuring 11 × 9 × 7 cm, encapsulated, grayish-white, and nodular. The H&E-stained sections showed a tumor composed of atypical spindle cells, large pleomorphic epithelioid cells, and multinucleated cells of osteoclastic type with osteoid formation with abundant areas having malignant chondroid matrix. About 40 atypical mitoses/10 HPF were seen. A diagnosis of primary osteosarcoma was made. Immunohistochemically, the tumor was triple negative, vimentin was strongly positive, SMA was focally positive, and AE1/AE3 was negative. The patient was put under observation. Her postoperative course is generally promising without any complaint of pain. We present a case of a very young female with the rarest diagnosis of primary osteosarcoma involving the left breast. Conclusion Primary osteosarcomas of the breast carry poor prognosis by being triple negative, and because of being the rarest tumors, they pose a challenge in managing the patients due to lack of established treatment modalities.

What's new in adipocytic neoplasia?

Adipocytic tumors are frequently encountered in routine practice, and while the vast majority represent commonly encountered tumor types (e.g., benign lipoma), the heterogeneity and rarity of other adipocytic neoplasms can pose diagnostic challenges. Atypical and malignant adipocytic tumors account for approximately 20% of all sarcomas. The 2013 World Health Organization (WHO) classification of soft tissue and bone tumors recognizes four major liposarcoma subtypes, characterized by distinct clinical behavior, distinctive morphologies, as well as unique genetic findings: atypical lipomatous tumor/well-differentiated liposarcoma, dedifferentiated liposarcoma, myxoid liposarcoma, and pleomorphic liposarcoma. Since the publication of the 2013 WHO classification of soft tissue and bone tumors, the most notable change in the category of adipocytic tumors has been made in the clinicopathologic and molecular characterization of the heterogeneous but distinct group of "atypical low-grade adipocytic neoplasms with spindle cell features," for which the term atypical spindle cell/pleomorphic lipomatous tumor has been proposed. Another substantive change in the group of adipocytic tumors is the introduction of pleomorphic myxoid liposarcoma (myxoid pleomorphic liposarcoma) as an apparently novel subtype of aggressive liposarcoma, especially occurring in children and young adults with a predilection for the mediastinum. This review will further focus upon the diagnostic criteria of these novel emerging entities in the group of adipocytic tumors.

PGR Gene Fusions Identify a Molecular Subset of Uterine Epithelioid Leiomyosarcoma With Rhabdoid Features.

Genetic aberrations among uterine epithelioid leiomyosarcomas are unknown. Following identification of an index case with NR4A3-PGR fusion demonstrating monomorphic morphologic features, we interrogated additional uterine tumors demonstrating similar histology and sought to describe the morphologic and immunohistochemical characteristics of PGR-rearranged sarcomas. Targeted next-generation RNA sequencing was performed on RNA extracted from formalin-fixed paraffin-embedded tissue of the index case. Fluorescence in situ hybridization using custom probes flanking PGR and NR4A3 genes was applied to 17 epithelioid leiomyosarcomas, 6 endometrial stromal tumors, and 3 perivascular epithelioid cell tumors. NR4A3-PGR fusion (n=4) and PGR rearrangement (n=2) were detected in 6 (35%) epithelioid leiomyosarcomas. Median patient age was 45 years, and all presented with FIGO stage I or II tumors, 2 being alive with disease at 75 and 180 months. All tumors were centered in the cervical stroma or myometrium and consisted of cells with abundant eosinophilic cytoplasm (epithelioid), including many displaying dense intracytoplasmic inclusions (rhabdoid). Myxoid matrix and hydropic change imparted a microcystic growth pattern in 4 tumors. Five also showed a minor spindle cell component which was low-grade in 3, consisting of bland spindle cells with low mitotic activity. High-grade spindle cell morphology was seen in 2 tumors, exhibiting a storiform pattern of atypical spindle cells associated with brisk mitotic activity. Desmin, estrogen receptor, and progesterone receptor were positive in all 6 tumors, while CD10 and HMB45 were negative. PGR rearrangements define a genetic subset of epithelioid leiomyosarcomas with often biphasic morphology consisting of epithelioid and rhabdoid as well as spindle cell components.

“Fat-Rich” (Spindle Cell-Poor) Variant of Atypical Spindle Cell/Pleomorphic Lipomatous Tumor: Striking Mimic of “Classical” Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma

We report the case of a "fat-rich" (spindle cell-poor) variant of an atypical spindle cell/pleomorphic lipomatous tumor in a 63-year-old female patient presenting with a firm, painless soft tissue mass on the right hip. Atypical spindle cell/pleomorphic lipomatous tumor is a very recently described low-grade adipocytic neoplasm, which occurs predominantly in adults with a predilection for the limbs and limb girdles. In the present case, the diagnosis of an atypical spindle cell/pleomorphic lipomatous tumor was challenging because the tumor was almost exclusively composed of an atypical adipocytic component (resembling "classical" atypical lipomatous tumor/well-differentiated tumor) with only very focal presence of the diagnostic atypical morphologic features (atypical spindle-shaped cells, floret-like multinucleated cells, and "bizarre" pleomorphic [multinucleated] cells). The possibility of a "classical" atypical lipomatous tumor/well-differentiated liposarcoma was ruled out by immunohistochemistry (lack of MDM2 expression and loss of Rb expression) and molecular genetic testing (no amplification of MDM2 and presence of monoallelic deletion of RB1). Another interesting morphologic observation in this case was the striking perivascular location of the atypical spindle/pleomorphic cells in some areas (so-called "pericytic mimicry"). To our knowledge, pericytic mimicry has not been reported in the setting of an atypical spindle cell/pleomorphic lipomatous tumor.

SUN-553 Atypical Spindle Cells on a Thyroid Aspirate: A Rare Case of a Thyroid Schwannoma Presenting as a Progressively Expanding Thyroid Nodule

Background: Mesenchymal tumors represent around 1% of all thyroid neoplasms. Schwannoma is one such tumor that arises from the peripheral nerve sheath within the thyroid gland. Case: A 40-year-old lady was referred to our center for evaluation of a thyroid mass that was initially noticed 2 years prior and had been rapidly enlarging over the past several months. The patient experienced occasional dysphagia, but no shortness of breath nor change in voice. There was no family history of thyroid cancer or exposure to head and neck radiation. On physical exam, a firm, non-tender, 3 cm nodule was palpated in the right thyroid lobe. There was no cervical lymphadenopathy. Pemberton sign was negative. There was no evidence of café-au-lait spots or cutaneous neurofibromas on skin exam. The thyroid function tests were normal (NL), with serum TSH of 2.06 µIU/mL (NL: 0.27 - 4.2) and free thyroxine of 1.2 ng/dL (NL: 0.9 - 1.7), anti-TPO antibody was elevated (483 IU/mL; NL: 0 - 34.9), serum calcitonin was undetectable (<5 pg/ml, NL <= 7.6 pg/ml), and serum PTH was NL (29.8 pg/ml; NL: 15 - 65). Thyroid ultrasound (US) revealed a solid, heterogeneous, hypoechoic, vascularized nodule, with regular borders and no microcalcifications, measuring 3.2cm x 1.7cm x 3.9cm - consistent with intermediate suspicion for malignancy per the American Thyroid Association risk stratification. There was no cervical lymphadenopathy. A CT scan of the neck revealed the mass causing mild tracheal deviation. A fine needle aspiration biopsy of the nodule revealed atypical spindle cells with hyperchromatic elongated nuclei and rare colloid, representing a spindle cell neoplasm. The patient underwent total thyroidectomy, right central neck lymph node dissection and a right cervical thymectomy. Histopathology was consistent with thyroid schwannoma characterized by a low Ki67 proliferation index, along with background Hashimoto’s thyroiditis. Immunohistochemical staining showed that the tumor cells were focally positive for TTF-1, negative for thyroglobulin and calcitonin and diffusely positive for S-100 and vimentin, further supporting the diagnosis of a schwannoma. Next generation sequencing of the DNA and RNA derived from tumor tissue using Oncomine Comprehensive Assay v3 detected NF2 p.Leu505fs frameshift mutation. The post-operative course was uneventful, and the patient was discharged on replacement levothyroxine. Upon 8 months follow-up, the patient continued to do well without any symptoms. Conclusion: Thyroid schwanommas are exceptionally rare, with around 20 cases reported to this day. Schwannomas may progressively enlarge causing compressive symptoms and mimicking more aggressive spindle cell tumors such as spindle cell papillary, medullary or anaplastic thyroid cancer and thyroid sarcomas. Prompt imaging and cytologic evaluation with appropriate ancillary studies is crucial in the management of these tumors.

A contemporary review of myxoid adipocytic tumors.

Myxoid adipocytic tumors encompass a broad heterogeneous group of benign and malignant adipocytic tumors, which are typically myxoid (e.g. myxoid liposarcoma, lipoblastoma and lipoblastoma-like tumor of the vulva) or may occasionally appear predominantly myxoid (e.g. pleomorphic liposarcoma, atypical lipomatous tumor, dedifferentiated liposarcoma, chondroid lipoma, spindle cell/pleomorphic lipoma, atypical spindle cell lipomatous tumor and atypical pleomorphic lipomatous tumor). There have been significant advances in recent years in classification and understanding the pathogenesis of adipocytic tumors, based on the correlation of histologic, immunohistochemical, and cytogenetic/molecular findings. Despite these advances, the morphologic diagnosis and accurate classification of a myxoid adipocytic tumor can be challenging due to major morphologic overlap between myxoid adipocytic and non-adipocytic tumors. This article will provide a review on the currently known morphological, immunohistochemical and molecular features of myxoid adipocytic tumors and their differential diagnosis.

Undifferentiated Uterine Sarcoma: A Rare Cause of Pelvic Pain in Young Woman

We report a case of undifferentiated uterine sarcoma occurring in a 20-year-old woman presenting as a pelvic pain with a mass discovered at the physical examination. The tumor ruptured into the abdominal cavity. A total hysterectomy was performed. On the pathological examination, the uterine corpus presents a proliferation of markedly atypical spindle cells admixed with round cells and pleomorphic cells. The tumor deeply infiltrated the myometrium. The tumor was very necrotizing. There were more than 50 mitoses per 10 fields at high magnification. The isthmus was invaded by the tumor. The diagnosis of undifferentiated uterine sarcoma was confirmed by immunohistochemistry. The tumor shows negativity for the following markers: CKAE1/AE3, h-caldesmon, α-SMA, progesterone receptors, desmin, CD 10, alpha foeto-protein, CD 3 and CD 20.

Diagnostic Immunohistochemistry for Soft Tissue and Bone Tumors: An Update.

Although some soft tissue and bone tumors can be identified based on histologic features alone, immunohistochemistry plays a critical diagnostic role for most mesenchymal tumor types. The discovery of recurrent genomic alterations in many benign and malignant mesenchymal neoplasms has added important biologic insights and expanded the spectrum of some diagnostic subgroups. Some tumors are defined by unique genomic alterations, whereas others share abnormalities that are not tumor-specific and can be observed in a sometimes broad range of biologically unrelated neoplasms. We herein focus on novel immunohistochemical markers, based on molecular genetic alterations, which are particularly useful in the diagnostic workup of selected groups of soft tissue and bone tumors, including recently described entities, specifically round cell sarcomas (Ewing sarcoma, CIC-rearranged sarcoma, and BCOR-rearranged sarcoma), vascular tumors (epithelioid hemangioma, epithelioid hemangioendothelioma, and pseudomyogenic hemangioendothelioma), SMARCB1-deficient neoplasms, adipocytic tumors (spindle cell/pleomorphic lipoma, atypical spindle cell lipomatous tumor, and conventional atypical lipomatous tumor), giant cell-rich bone tumors (giant cell tumor of bone and chondroblastoma), and biphenotypic sinonasal sarcoma. Given the complex nature of sarcoma classification, and the rarity of many mesenchymal tumor types, careful integration of clinical presentation, imaging features, histology, immunophenotype, and cytogenetic/molecular alterations is crucial for accurate diagnosis of soft tissue and bone tumors.

SYSTEMIC MASTOCYTOSIS WITH NORMAL BIOMARKERS. HOW VALUABLE ARE MAST CELL MEDIATORS IN IDENTIFYING DISEASE?

Introduction Systemic Mastocytosis (SM) is a disorder characterized by the excessive accumulation and activation of mast cells (MC) in various organs. Many biomarkers have proven to be helpful in disease screening and diagnosis. Namely, serum tryptase, urinary N-methylhistamine, leukotriene E4 (LTE4) and prostaglandin F2 alpha (PGF2α). Our purpose is to describe a case of Indolent SM (ISM) with normal MC biomarkers. Case Description This is a 30 y.o. female who presented with a 10-year history of headaches, clouding of consciousness, syncope, intermittent abdominal pain, nausea, diarrhea, bone pain, skin flushing and suspected episodes of anaphylaxis. Serum tryptase, 24-hour urinary N-methylhistamine, PGF2α and LTE4 were all within normal limits. Blood molecular studies confirmed KITD816V point mutation. Skin biopsy showed mastocytosis with features of telangiectasia macularis eruptiva perstans. Bone scan was consistent with bony remodeling for MC disease. Ultimately, bone marrow (BM) biopsy showed low-level (25%) exhibiting an atypical spindle shape morphology, immunohistochemistry detected aberrant CD5 and CD2 co-expression confirming SM. Discussion Cutaneous and ISM have a good prognosis with similar survival rates compared to the general population. However, close monitoring may be warranted in SM patients, since a low-rate progression has been reported. The relationship between biomarkers and symptomatology and MC burden is not completely understood nor are the sensitivities of the tests. In the right clinical setting, clinicians should proceed with bone marrow biopsy, immunohistochemistry and molecular studies for a prompt and accurate diagnosis regardless of the status of the above mentioned serum and urine MC biomarkers. Systemic Mastocytosis (SM) is a disorder characterized by the excessive accumulation and activation of mast cells (MC) in various organs. Many biomarkers have proven to be helpful in disease screening and diagnosis. Namely, serum tryptase, urinary N-methylhistamine, leukotriene E4 (LTE4) and prostaglandin F2 alpha (PGF2α). Our purpose is to describe a case of Indolent SM (ISM) with normal MC biomarkers. This is a 30 y.o. female who presented with a 10-year history of headaches, clouding of consciousness, syncope, intermittent abdominal pain, nausea, diarrhea, bone pain, skin flushing and suspected episodes of anaphylaxis. Serum tryptase, 24-hour urinary N-methylhistamine, PGF2α and LTE4 were all within normal limits. Blood molecular studies confirmed KITD816V point mutation. Skin biopsy showed mastocytosis with features of telangiectasia macularis eruptiva perstans. Bone scan was consistent with bony remodeling for MC disease. Ultimately, bone marrow (BM) biopsy showed low-level (25%) exhibiting an atypical spindle shape morphology, immunohistochemistry detected aberrant CD5 and CD2 co-expression confirming SM. Cutaneous and ISM have a good prognosis with similar survival rates compared to the general population. However, close monitoring may be warranted in SM patients, since a low-rate progression has been reported. The relationship between biomarkers and symptomatology and MC burden is not completely understood nor are the sensitivities of the tests. In the right clinical setting, clinicians should proceed with bone marrow biopsy, immunohistochemistry and molecular studies for a prompt and accurate diagnosis regardless of the status of the above mentioned serum and urine MC biomarkers.

Lentigo maligna and lentigo maligna melanoma: a clinicopathologic analysis of twenty-four cases

Objective: To study the clinicopathologic features, differential diagnosis and prognosis of lentigo maligna (LM) and lentigo maligna melanoma (LMM). Methods: Histopathologic evaluation and immunohistochemical study by HRP multimer method were carried out in 24 cases of LM and LMM from 2012 to 2017 at Fudan University Shanghai Cancer Center. The clinical information and follow-up data were analyzed. Results: Of total 24 cases, there were 7 cases of LM and 17 cases of LMM; 10 males and 14 females. The age of patients ranged from 32 to 88 years (mean 67 years). The male-to-female ratio was 1.0∶1.4. Tumors were all located on head and face. Clinically, all patients presented with mottled light brown or sepia macule located on head and face for a long time, and some of them followed by nodules or ulceration within the lesion. The diameter of lesions ranged from 0.5 to 3.0 cm. Microscopically, LM and in-situ component of LMM were all characterized by a predominantly junctional proliferation of atypical melanocytes with marked pleomorphism, frequently extending down the walls of hair follicles and sweat ducts. Multinucleate cells were frequently present. The invasive components of LMM mainly consisted of atypical melanocytic spindle cells (13 cases, 76.5%), and the mean Breslow thickness was 1.2 mm (0.1-2.7 mm). The lesions of LM/LMM were generally associated with severe actinic damage, scattered infiltration of lymphocytes and melanophages. Statistically, the number of cases whose diameter of lesion ≥0.6 cm, mitotic rates ≥4/mm(2) and nests of melanocytes within epidermis in group of LMM were significantly more than those in group of LM. Immunohistochemically, atypical melanocytes in LM and LMM were generally positive for S-100, HMB45, PNL2, Melan A and SOX-10. Follow-up was available in all cases, ranging from 1 to 64 months. Only one out of 23 patients with wide surgical excision had local recurrence, and the remaining 22 patients were all alive with no evidence of disease. One LM patient who was merely treated with biopsy was alive with disease progression after 20 months follow-up. Conclusions: LM/LMM is a special subtype of melanoma predominantly located on the sun-exposed skin of elderly people. Recognition of its specific histologic features can help distinguish with sun-damaged diseases and other subtypes of melanoma. The prognosis of LM/LMM patients treated with surgical excision is considered relatively favorable. However, long term follow-up should be recommended in patients with LM/LMM because of high recurrence rates indicated by previous studies.

Metastatic Leiomyosarcoma Presenting as a Pancreatic Mass and Small Bowel Obstruction

Leiomyosarcomas are rare smooth muscle cell tumors that primarily originate in the retroperitoneum, genitourinary tract, and gastrointestinal tract. However, among soft-tissue sarcomas, they are a fairly common subtype, accounting for 10-20% of soft-tissue sarcomas. The recurrence rate of leiomyosarcoma is quite high, ranging from 26% to 51%, and dependent upon the origin of the primary lesion. Metastatic tumors are typically detected in the lungs and liver. Metastases to the liver from a primary extremity leiomyosarcoma are rare, and metastases to the pancreas regardless of cancer are very rare in themselves. Here we present the case of a patient with previous history of leiomyosarcoma of the right thigh (Fig. 1), which was treated medically with chemotherapy and radiation, as well as surgical resection. The patient later presented with abdominal pain and elevated amylase and lipase. Computed tomography imaging identified a mass in the head of the pancreas and liver (Fig. 2). Endoscopic ultrasound-guided fine-needle aspiration biopsy of the pancreatic mass demonstrated atypical spindle cell stromal fragments staining positive for the SMMS-1 and actin proteins and negative for desmin. Laparoscopy was performed for staging and biopsy of the liver and confirmed metastatic leiomyosarcoma. While recovering from surgery, the patient developed a closed loop small bowel obstruction (Fig. 3). Urgent surgery discovered a bowel obstruction secondary to intussusception of a metastatic tumor located within the wall of the jejunum. The current plan for the patient's pancreatic and liver lesions is cytotoxic chemotherapy, such as gemcitabine-based therapy, and screening for possible GPC3-CD3 BiTE therapy. This case provides a unique presentation of several rare leiomyosarcoma metastases in a single patient and demonstrates the common recurrence of metastases in these particular types of cancers.2925_A Figure 1. Short TI inversion recovery (STIR) MR image depicting a 4.9 x 1.9 cm mass intra-articular mass within the suprapatellar recess and deep to the medial patellar retinaculum within the right knee.2925_B Figure 2. CT imaging of the abdomen and pelvis with contrast. Arrow demonstrates a 1.7 x 1.3 cm hypodense lesion within the head of the pancreas.2925_C Figure 3. CT imaging of the abdomen and pelvis with contrast. Arrows demonstrate a 1.8 x 1.5 cm enhancing lesion within the small bowel. Bottom images were taken 3 days after top images and demonstrate dilation of the small bowel.

Atypical spindle cell/pleomorphic lipomatous tumor: A clinicopathologic, immunohistochemical, and molecular study of 20 cases.

Lipomatous tumors accompanied by spindle cell component are not frequently encountered, and there are still problems regarding their differential diagnosis, nature, and nomenclature. To contribute to ongoing efforts, we present the clinical, histologic, and immunohistochemical characteristics of 20 cases of spindle cell lipomatous tumors with atypical features that may also be called atypical spindle cell/pleomorphic lipomatous tumors. Of the patients, 13 were men and 7 were women with an average age of 57.5 years. The most commonly affected site was the extremities. Twelve tumors arose in the subcutaneous tissue, while eight cases were located in the deep soft tissues. Tumor margins were often ill-defined with invasion into the surrounding tissues. Microscopic examination revealed a wide spectrum of histologic features. All cases consisted of poorly marginated proliferation of mildly atypical spindle cells set in a fibrous or myxoid stroma with a variable amount of adipocytic component showing variation in adipocyte size and scattered nuclear atypia and frequent univacuolated or multivacuolated lipoblasts. Tumor cellularity and the relative proportion of the components were highly variable. One tumor showed morphologic features evocative of dedifferentiation and another one exhibited histological features resembling pleomorphic liposarcoma. None of the patients had recurrence or metastasis at follow-up.

Dedifferentiated parosteal osteosarcoma of the maxilla: a case report and review of the literature

BackgroundParosteal osteosarcomas are usually low-grade tumors, however, sometimes they transform to high-grade tumors, which is named dedifferentiation. This phenomenon has been reported in long bones. Recently, we encountered a patient with dedifferentiated parosteal osteosarcoma occurring in the maxilla. Here, we report a first case of dedifferentiated parosteal osteosarcoma of the head and neck region.Case presentationA 45-year-old Japanese woman with a refractory bone lesion in the maxilla presented to our hospital. A biopsy showed atypical spindle cell proliferation involving dedifferentiated high-grade component, which was diagnosed as dedifferentiated parosteal osteosarcoma. Three cycles of neoadjuvant chemotherapy using ifosfamide and pirarubicin were performed followed by sub-total maxillectomy. Histopathological results showed that neoadjuvant chemotherapy was effective for high-grade component. The decision to perform adjuvant chemotherapy (cisplatin and pirarubicin) was made because distant metastasis has been reported, even in cases with dedifferentiated parosteal osteosarcoma in which complete necrosis of high-grade component was achieved due to neoadjuvant chemotherapy. There was no recurrence 15 months after surgery.ConclusionsDedifferentiated parosteal osteosarcoma can occur in the head and neck region. Chemotherapy including anthracycline anticancer agent could be effective for high-grade component of dedifferentiated parosteal osteosarcoma.

Lipofibromatosis-like neural tumour: a clinicopathological study of ten additional cases of an emerging novel entity

We present our experience with ten cases of lipofibromatosis-like tumour (LPF-NT) to further characterise this newly described neoplasm. There were six males and four females with a mean age of 12.8 years (range 2-37 years). Tumours occurred in the neck (n=3), buttock (n=2), chest wall, flank, hip, hand and foot (n=1). Histologically, they were composed of cellular fascicles of mildly to moderately atypical spindle cells displaying an infiltrative pattern reminiscent of lipofibromatosis or dermatofibrosarcoma protuberans. Immunohistochemically, all cases co-expressed S100 protein and CD34. FISH analysis revealed NTRK1 gene rearrangement in four of five cases tested. Clinical follow-up showed local recurrence in three cases but no evidence of metastasis. This study further supports that LPF-NT represents a novel entity of NTRK1-associated neoplasms. Awareness of its clinicopathological features, immunophenotypes and cytogenetic abnormalities helps pathologists arrive at the correct diagnosis.

Pleomorphic and dedifferentiated leiomyosarcoma: a clinicopathologic analysis

Objective: To investigate the clinicopathologic features, differential diagnosis and biological behavior of pleomorphic leiomyosarcoma (PLMS) and dedifferentiated leiomyosarcoma (DLMS). Methods: Forty-nine cases were collected from November 2007 to December 2016, including eight that diagnosed at Fudan University Shanghai Cancer Center, and 41 consultation cases. The clinical findings and pathologic features were reviewed. Immunophenotype was obtained in 33 cases and follow-up information was available in 38 cases. Results: There were 22 males and 27 females with ages ranging from 24 to 83 years (mean 52.5 years). Fifteen cases occurred in extremities, 14 in deep body cavity, 11 in the trunk, 4 in the head and neck, 2 in the bladder, and 1 each in the inguinal region, perineum and femoral vein, respectively. Tumor sizes ranged from 3 to 30 cm (mean 9.1 cm). The tumors were composed of at least small foci of typical leiomyosarcoma (LMS) and areas of high-grade pleomorphic/undifferentiated sarcoma. The typical LMS component showed the characteristic morphology of smooth muscle differentiation and was low to intermediate grade in most cases. Pleomorphic areas were mainly composed of atypical spindle and polygonal cells admixed with variable large, bizarre atypical cells and multinuclear giant cells, mostly mimicking undifferentiated pleomorphic sarcoma. The pleomorphic and leiomyosarcomatous areas were usually intermixed, but the demarcation may be distinct or gradual in some cases. The classical LMS component was positive for at least one myogenic marker: α-SMA in 97.0%(32/33), desmin in 72.7%(24/33), H-caldesmon in 90.9% (20/22), MSA in 14/16, and calponin in 15/15 of cases. The pleomorphic sarcoma component was reactive for at least one myogenic marker in 87.9% (29/33) of cases, usually showing focal and less intense immunoreactivity than classical LMS component: α-SMA was positive in 81.8%(27/33), desmin in 48.5%(16/33), H-caldesmon in 72.7% (16/22), MSA in 12/16, and calponin in 11/15 of cases. Based on staining for muscle markers in the pleomorphic component, 29 cases were designated as PLMS, 4 as DLMS. Ki-67 index ranged from 15% to 70% (mean 40%). Follow-up data was available in 38 cases (77.6%), of which 11 patients (28.9%) died of disease, 12 patients were alive with unresectable or recurrent disease, 14 patients were alive with no evidence of disease and another one died of unrelated cause. The median disease-free and overall survival was 6 and 10 months respectively. Twelve patients exhibited local recurrence and 11 developed metastases. The median interval to progression was 8 months. Conclusions: The identification of areas of typical LMS is crucial for accurate diagnosis of PLMS and DLMS. Both PLMS and DLMS show more aggressive behavior and poorer prognosis than ordinary LMS.

Clinicopathologic features of atypical spindle cell lipomatous tumor

Objective: To investigate the clinicopathologic characteristics, immunophenotype, differential and diagnostic features of atypical spindle cell lipomatous tumor (ASLT). Methods: Three cases of ASLT were collected from January 2010 to March 2017 at Zhejiang Provincial People's Hospital. The clinical and imaging features, histomorphology, immunophenotype and prognosis were analyzed. Fluorescence in situ hybridization (FISH) was used to detect MDM2 gene amplification, and relevant literature was reviewed. Results: All three patients were adult males, aged 38, 43 and 54 years, respectively. One tumor originated in the subcutaneous soft tissue in the head and neck, one was located in the left primary bronchus and one in the latissimus dorsi muscle. Grossly, all three tumors were circumscribed and ranged from 4.0 to 5.8 cm in size. Microscopically, all showed a focally infiltrative front. These tumors were composed of variable proportions of spindle-shaped and adipocytic cells in a background of variable fibrous and edematous matrix. Scattered lipoblasts were easily seen. One tumor was composed predominately of spindle tumor cells, one of adipocytic cells, and one of equally mixed cell populations. The spindle tumor cells were generally bland-appearing with focal nuclear enlargement and hyperchromasia noted in one case. Mitosis was not seen in neither the spindle cells nor the adipocytic cells. By immunohistochemistry, diffuse and strong reactivity to CD34 of the spindle cells was noted in all cases, definite loss of Rb expression was noted in one of three cases, and S-100 protein was expressed only in the adipocytic cells. INI-1 was intact and Ki-67 index was 1% to 3%. All other markers including CDK4, MDM2, STAT6, SOX10, CD99, bcl-2, β-catenin, CD117, GFAP, CK, EMA, SMA and desmin were negative. FISH of MDM2 was done in two cases, and both showed no amplification. The ASLT in the head and neck had two recurrences during 17 months of follow-up, whereas the tumor in the latissimus dorsi was free of disease during 33 months of follow-up. Conclusions: ASLT is a rare subtype of low-grade adipocytic neoplasm and is distinctive from atypical lipomatous tumor/well-differentiated liposarcoma. The histomorpholgy of ASLT has significant heterogeneity and forms a continuous spectrum. ASLT needs to be distinguished from a series of benign and malignant soft tissue tumors.

Carcinosarcoma of Stomach Confined to the Mucosa.

Carcinosarcoma is a malignant tumor composed of both epithelial and mesenchymal malignant tumor components. A 78-year-old man was transferred to our hospital because of hematemesis and tarry stool. An emergency gastrointestinal endoscopic examination revealed active bleeding from an ulcerative lesion on the posterior wall of the gastric body; endoscopic hemostasis was successfully performed. A gastrointestinal endoscopy performed two months later showed a polypoid lesion at the same place where the ulcer had been. The biopsy specimen was histologically diagnosed as well to moderately differentiated tubular adenocarcinoma. The patient underwent a laparoscopic distal gastrectomy with D2 lymph node dissection under a diagnosis of gastric adenocarcinoma. A 28 × 15 mm polypoid tumor was resected from the gastric body, and was found on microscopic examination to consist of both carcinoma and sarcoma components, showing atypical spindle cells, which were positive for α-smooth muscular actin, calponin, and h-caldesmon, but negative for CD34, CD117 (c-kit), desmin, and dog 1. These findings led to a diagnosis of gastric carcinosarcoma. The tumor was confined to the mucous membrane. Lymph node metastasis was found in one node and contained only the carcinoma component. The postoperative course was uneventful. The patient lived without recurrence for 2 years. Carcinosarcoma of the stomach is a rare tumor with high malignant potential and poor prognosis. Careful follow up is required for early detection of any recurrence.