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Case Presentation A 35-year-old woman with no known medical history presented to the ED with complaints of progressive dyspnea for several months. The patient also reported episodic cough with yellow to green sputum production. She denied fever, chills, weight loss, or hemoptysis. She also denied any history of previous lung diseases in her family. She denied any history of tobacco or recreational drug use or any exposures. She was originally from El Salvador and immigrated to the United States approximately 3 years earlier. She was evaluated in El Salvador at age 15 for "lung issues" but had never received a formal diagnosis.

Nucleophosmin-anaplastic lymphoma kinase-expressing (NPM-ALK+ ) T-cell lymphoma is an aggressive neoplasm that is more commonly seen in children and young adults. The pathogenesis of NPM-ALK+ T-cell lymphoma is not completely understood. Wild-type ALK is a receptor tyrosine kinase that is physiologically expressed in neural tissues during early stages of human development, which suggests that ALK may interact with neurotrophic factors. The aberrant expression of NPM-ALK results from a translocation between the ALK gene on chromosome 2p23 and the NPM gene on chromosome 5q35. The nerve growth factor (NGF) is the first neurotrophic factor attributed to non-neural functions including cancer cell survival, proliferation, and metastasis. These functions are primarily mediated through the tropomyosin receptor kinase A (TrkA). The expression and role of NGF/TrkA in NPM-ALK+ T-cell lymphoma are not known. In this study, we tested the hypothesis that TrkA signaling is upregulated and sustains the survival of this lymphoma. Our data illustrate that TrkA and NGF are expressed in five NPM-ALK+ T-cell lymphoma cell lines and TrkA is expressed in 11 of 13 primary lymphoma tumors from patients. In addition, we found evidence to support that NPM-ALK and TrkA functionally interact. A selective TrkA inhibitor induced apoptosis and decreased cell viability, proliferation, and colony formation of NPM-ALK+ T-cell lymphoma cell lines. These effects were associated with downregulation of cell survival regulatory proteins. Similar results were also observed using specific knockdown of TrkA in NPM-ALK+ T-cell lymphoma cells by siRNA. Importantly, the inhibition of TrkA signaling was associated with antitumor effects in vivo, because tumor xenografts in mice regressed and the mice exhibited improved survival. In conclusion, TrkA plays an important role in the pathogenesis of NPM-ALK+ T-cell lymphoma, and therefore, targeting TrkA signaling may represent a novel approach to eradicate this aggressive neoplasm.

Introduction/Objective SMARCA4 (BRG1) is a central component of the Switch/Sucrose-Non-Fermentable (SWI/SNF) chromatin remodeling complex which plays a critical role in the initiation, progression and dedifferentiation of a variety of cancers arising in different anatomical sites. The recently discovered SMARCA4-deficient thoracic sarcoma (DTS) can present as a mediastinal, pleural or pulmonary mass and constitutes a unique and highly lethal entity. Methods Here we present an interesting case of a 66-year-old, smoker male with past medical history of COPD, polysubstance abuse, hepatitis C virus, and alcoholic cirrhosis who presented with left proximal tibia pathological fracture, L5 vertebral body lytic lesion, left leg cellulitis and hypercalcemia. Imaging studies, tibia biopsy, thoracocentesis, histopathological examination, and immunohistochemical stains were performed. Results Imaging studies revealed a 3.1 cm, right upper lobe speculated lung mass along with multiple other lung nodules. Numerous arterially enhancing hepatic masses up to 2.8 cm were also identified. The patient underwent intramedullary nail, cementation and tibia biopsy followed by thoracentesis a month later.The histological sections revealed sheets of poorly differentiated malignant epithelioid cells showing high nuclear pleomorphism, prominent nucleoli, eosinophilc cytoplasm with extensive necrosis, and high mitosis (Ki-67 around 100%). The tumor cells lacked the expression of SMARCA4 (BRG1), cytokeratin, SALL4, CD34, TTF-1, P40, S100, HMB45, pan melanoma, desmin, CD31, ERG, CD30, CD56, chromogranin, CD38, CD45, CD3, ALK-1, myeloperoxidase, glypican-3, hepatocyte, and inhibin with mixed kappa and lambda. Tumor cells expressed SATB2 and focal synaptophysin, consistent with SMARCA4 deficient thoracic sarcoma metastasizing to the bone. The patient’s condition rapidly deteriorated and he died within two months. Conclusion An accurate diagnosis of these tumors is paramount and can be challenging. However, recognizing SMARCA4-DTS from other types of epithelioid tumors that involve the thoracic region is clinically relevant, as targeted therapies for SMARC-deficient tumors are currently being investigated and new clinical trial data show therapeutic benefit.

Male breast cancer represents1% of breast cancers, with invasive lobular carcinoma in male breast being extremely rare. Only four cases of male breast with pleomorphic lobular carcinoma (PLC) are reported in literature. Here, we report two additional cases. The first case was a 63-year old male presenting with a left neck mass, progressive facial numbness, bilateral cervical lymphadenopathy, and brain metastasis. Neck mass and left breast biopsies confirmed left breast PLC with metastasis. The second case was a 79-year old male with a left breast mass; biopsy and subsequent mastectomy showed PLC. Awareness of this entity is important for rendering an accurate diagnosis, especially in the setting of metastases.

Boerhaave syndrome is a transmural disruption of the esophagus, due to an increase in esophageal pressure and is associated with high morbidity and mortality. There are cases reported secondary to bowel obstructions such as incarcerated hernias and gallstone ileus. Here, we describe an unusual autopsy case of Boerhaave syndrome, due to bowel obstruction secondary to biliary adenocarcinoma, which has never been reported in the literature. The patient was an 87-year old male presenting with severe chest and epigastric pain. Computed tomography showed fluid-filled esophagus, gastric distention and an ill-defined mass within the liver. Patient underwent esophagogastroduodenoscopy, which revealed esophageal rupture. Patient expired within 20 hours of admission. On autopsy, the decedent was found to have an esophageal perforation and an inferior hepatic mass, which morphologically and immunohistochemically was consistent with a biliary adenocarcinoma.

Background Sarcomatoid carcinoma, or carcinosarcoma, is a neoplasm that contains both sarcomatous and carcinomatous elements. It is an extremely rare cancer most often arising from visceral organs. Here we report the seventh documented de novo case of carcinosarcoma of the bone, in a young female who showed initial clinical improvement with gemcitabine and docetaxel. Case presentation A 36-year-old Caucasian female presented with diffuse musculoskeletal pain that had progressed from her shoulder to her back, arm, and knee over 6 months. Imaging revealed diffuse sclerotic lesions of bilateral humeral heads, iliac and ischial bones, and thoracic and lumbar spine. Histopathologic examination of biopsies from the T9 vertebra and left femur showed mainly sarcomatous spindle cells with focal osteoid production. Immunostaining showed the cells to be OSCAR cytokeratin, patchy positive for pankeratin, and negative for CK7, GATA3, S100, SOX10, CD99, EMA, AE1/AE3, and HMW keratin indicative of an epithelial origin. After thorough clinical correlation, sarcomatoid carcinoma of a visceral organ was excluded and the diagnosis of primary sarcomatoid carcinoma of the bone was ultimately favored. She received chemotherapy with gemcitabine and docetaxel, and showed improvement at 6 months but ultimately passed 1 year post diagnosis. Conclusions Primary carcinosarcoma of the bone is an extremely rare malignancy. Early diagnosis is crucial as localized disease may be curable with resection. As shown in this case, combination chemotherapy with gemcitabine and docetaxel is a potential option in patients with unresectable or metastatic disease.

Introduction/Objective Chordoma is a rare tumor most commonly arising in the sacrococcygeal region from notochord remnants. Usually, these tumors are locally invasive and recurrent, but do not have the capability to metastasize. A newly described aggressive variant called poorly differentiated chordoma is different than conventional chordoma in that it does not have the well-differentiated histologic appearance of conventional chordoma and also exhibits loss of SMARCB1/INI1. Methods Herein, we describe a case of poorly differentiated chordoma with SMARCB1/INI1 loss, concurrent TP53 mutation and Rb1 loss. Results The patient is a 55-year-old man with a history of a previously resected sacrococcygeal chordoma, who was found to have new hepatic, lung, and adrenal lesions. Biopsy of the liver showed sheets of malignant epithelioid cells with vacuolated cytoplasm, areas of necrosis, and up to 5 mitoses in one high power field. No physaliferous features or matrix material were seen. After an extensive panel of immunohistochemical markers, the origin of the metastatic tumor could not be determined and the tumor was only positive for Cam5.2, EMA, and CD56. Brachyury was performed due to the patient’s previous history and was positive. Genomic testing showed a SMARCB1 mutation, a TP53 mutation, and RB1 loss. Additional markers were performed and the tumor showed a Ki-67 proliferation index of approximately 80%, mutant p53 protein, loss of INI1, and strong expression of prometastatic CXCR4 and the histone methyltransferase EZH2. The most recent follow-up of the patient showed that the patient was receiving palliative care. Conclusion Poorly differentiated chordoma is a highly aggressive variant of chordoma with few cases reported. This case of SMARCB1/INI-deficient, poorly differentiated chordoma also showed concurrent TP53 mutation and loss of RB1, which resulted in malignant transformation with loss of differentiation, cell cycle progression, up-regulation of prometastatic CXCR4 and the histone methyltransferase EZH2 causing aggressive behavior and metastasis.

Introduction/Objective Gastrointestinal stromal tumor (GIST) arises from the interstitial cell of Cajal. 30% of GISTs arise in the jejunum. GISTS are generally solitary although multiple GISTs may be synchronous or metachronous. There are a few reports of a GIST of the jejunum mimicking a vascular malformation/arteriovenous malformation (AVM) prior to surgical excision. Methods Herein, we report a case of four synchronous GISTs of jejunum. One GIST, highly vascularized, presented with lower gastrointestinal bleeding. The patient was a 40-year-old female presenting with epigastric pain and melena. Results She was found to have an ulcerated lesion in the distal jejunum by capsule enteroscopy and double balloon enteroscopy, interpreted as an arteriovenous malformation and tattooed. Several other non-ulcerated “polyps” were described. Gross examination of the ensuing segmental resection of jejunum demonstrated four bosselated tumors ranging from 3.1 cm to 6.5 cm. Microscopically, three tumors did not extend to the surface of the jejunum and were predominantly composed of spindle cells. One tumor (identified by tattoo) extended to the surface with ulceration. This tumor was dominated by wide vascular channels with a spindle cell component between the channels. The four tumors were each positive for CD117, DOG1, and Succinate dehydrogenase B (SDH), identifying the four tumors as non-SDH-deficient GISTs. Ki-67 proliferation index was less than 5% in all four masses. Conclusion Multiple GISTs are rare, classified as either sporadic or familial. Familial GEISTs are described in neurofibromatosis type 1, Carney’s triad and Carney-Stratakis syndrome. Pediatric GISTs, with clinical and genetic features often differing from typical adult tumors may also be multiple. Our patient’s four GISTs are considered multiple synchronous sporadic neoplasms. This case serves as an important reminder for pathologists consider GIST in the evaluation of a highly vascular gastrointestinal proliferation and keep in mind the possibility of multiplicity.

Human papillomavirus–related adenocarcinomas account for approximately 20% of all cervical cancers. Most of them arise in the transformation zone but may be found exclusively in endocervical canal. Contiguous spread into the lower uterine segment is known to occur, but finding a “skip” lesion in a fundal endometrial polyp poses an interesting pathologic conundrum. We present a case of a 57-year-old woman with a history of postcoital bleeding and abnormal cervical smear. Cervical exam showed a 2-cm exophytic mass on anterior cervix. Biopsy revealed invasive endocervical adenocarcinoma. Patient underwent radical hysterectomy. Gross examination revealed large cervical mass without involvement of low uterine segment and a benign-appearing small uterine fundal polyp. Microscopic examination confirmed the deeply invasive endocervical adenocarcinoma, and the benign-appearing endometrial polyp had similar atypical glands on the polyp surface and admixed with benign endometrial glands. Both cervical tumor and the carcinoma involving endometrial polyp demonstrated identical immunohistochemistry showing diffuse positive p16 and CEA(m) and negative for ER and vimentin. The authors report a rare case of endocervical adenocarcinoma with skip lesion in the endometrial fundal polyp, and rare cases with skip lesion in the fallopian tubes from endocervical adenocarcinoma have been reported in the literature. High clinical suspicion and ancillary immunohistochemistry are necessary to differentiate the lesion from endometrioid or papillary carcinoma arising from endometrial polyp.

Nucleophosmin‐anaplastic lymphoma kinase‐expressing (NPM‐ALK +) T‐cell lymphoma is an aggressive neoplasm that is more commonly seen in children and young adults. The pathogenesis of NPM‐ALK + T‐cell lymphoma is not completely understood. Wild‐type ALK is a receptor tyrosine kinase that is physiologically expressed in neural tissues during early stages of human development, which suggests that ALK may interact with neurotrophic factors. The aberrant expression of NPM‐ALK results from a translocation between the ALK gene on chromosome 2p23 and the NPM gene on chromosome 5q35. The nerve growth factor (NGF) is the first neurotrophic factor attributed to non‐neural functions including cancer cell survival, proliferation, and metastasis. These functions are primarily mediated through the tropomyosin receptor kinase A (TrkA). The expression and role of NGF/TrkA in NPM‐ALK + T‐cell lymphoma are not known. In this study, we tested the hypothesis that TrkA signaling is upregulated and sustains the survival of this lymphoma. Our data illustrate that TrkA and NGF are expressed in five NPM‐ALK + T‐cell lymphoma cell lines and TrkA is expressed in 11 of 13 primary lymphoma tumors from patients. In addition, we found evidence to support that NPM‐ALK and TrkA functionally interact. A selective TrkA inhibitor induced apoptosis and decreased cell viability, proliferation, and colony formation of NPM‐ALK + T‐cell lymphoma cell lines. These effects were associated with downregulation of cell survival regulatory proteins. Similar results were also observed using specific knockdown of TrkA in NPM‐ALK + T‐cell lymphoma cells by siRNA. Importantly, the inhibition of TrkA signaling was associated with antitumor effects in vivo, because tumor xenografts in mice regressed and the mice exhibited improved survival. In conclusion, TrkA plays an important role in the pathogenesis of NPM‐ALK + T‐cell lymphoma, and therefore, targeting TrkA signaling may represent a novel approach to eradicate this aggressive neoplasm.