• We present a case of dyskeratosis congenita (DC) caused by germline TINF2 mutation. • Autopsy samples reveal multisystem telomere shortening. • Pediatric bone marrow failure patients should be screened for telomere gene mutations. Dyskeratosis congenita is a disease of impaired tissue maintenance downstream of telomere dysfunction. Characteristically, patients present with the clinical triad of nail dystrophy, oral leukoplakia, and skin pigmentation defects, but the disease involves degenerative changes in multiple organs. Mutations in telomere-binding proteins such as TINF2 (TRF1-interacting nuclear factor 2) or in telomerase, the enzyme that counteracts age related telomere shortening, are causative in dyskeratosis congenita. We present a patient who presented with severe hypoxemia at age 13. The patient had a history of myelodysplastic syndrome treated with bone marrow transplant at the age of 5. At age 18 she was hospitalized for an acute pneumonia progressing to respiratory failure, developed renal failure and ultimately, she and her family opted to withdraw support as she was not a candidate for a lung transplant. Sequencing of the patient’s TINF2 locus revealed a heterozygous mutation (c.844C > T, Arg282Cys) which has previously been reported in a subset of dyskeratosis congenita patients. Tissue sections from multiple organs showed degenerative changes including disorganized bone remodeling, diffuse alveolar damage and small vessel proliferation in the lung, and hyperkeratosis with hyperpigmentation of the skin. Autopsy samples revealed a bimodal distribution of telomere length, with telomeres from donor hematopoietic tissues being an age-appropriate length and those from patient tissues showing pathogenic shortening, with the shortest telomeres in lung, liver, and kidney. We report for the first time a survey of degenerative changes and telomere lengths in multiple organs in a patient with dyskeratosis congenita.

• Sclerosing mucoepidermoid carcinoma with eosinophilia (SMCE) is a rare. • SMCE is an under-recognized subgroup of mucoepidermoid carcinoma. • SMCE is characterized by dense sclerotic stroma with marked eosinophil infiltration. • Here are added two cases with no clear split signals confirmed in FISH for MAML2 . • SMCE is possibly unique in histogenesis as well as genetic backgrounds. Sclerosing mucoepidermoid carcinoma with eosinophilia (SMCE) is a rare subgroup of mucoepidermoid carcinoma characterized by dense stromal sclerosis and marked eosinophil infiltration. We herein describe two Japanese cases of SMCE. The patients were a 60 year-old female and a 67 year-old female, and each had a tumor of the parotid and upper lip, both of which were successfully removed with no signs of recurrence or metastasis. Histologically, the tumors consisted of round or polygonal, and partly spindle-shaped squamous cells with generally scant keratinization, which formed small and large invasive nests in the background of dense sclerotic stroma with marked eosinophil infiltration. Only a small number of mucus-producing cells and cytoplasmic mucin vacuoles were observed. The second case was unique in its presentation of melanin pigmentation, which is rarely found in oral tumors. Fluorescence in situ hybridization for MAML2 was performed, but no clear split signals were confirmed in either case. The histogenesis of SMCE, which is possibly different to that of ordinary mucoepidermoid carcinoma or the other counterpart of sclerosing mucoepidermoid carcinoma lacking eosinophilia, is further discussed comparing their genetic backgrounds. Their pathological features and diagnostic problems are also detailed.

Childhood rhabdomyosarcoma (RMS) of perineal or perianal origin (PRMS) is rare, accounting for only 2% of all RMSs. PRMS has been reported to show different characteristics depending on the patient’s age, and patients aged 10 years or older have a poor prognosis. Disseminated intravascular coagulation (DIC) is considered to be an uncommon complication of RMS. However, it could occur occasionally in patients with widespread RMS with bone marrow infiltration. Pulmonary lymphangitic sarcomatosis (PLS) has been reported to be rare, and to our knowledge, only 18 cases (including 4 patients with RMS) have been reported to date. A 15-year-old female patient with suspected RMS was admitted to our hospital. The patient was diagnosed with PRMS following radiological evaluations and effusion cytology, and chemotherapy was initiated on the 6th day of admission. During the course, the patient suffered from severe dyspnea and DIC. Despite treatment, the bleeding tendency did not improve, and hepatic and renal failure progressed. The patient died of progressive respiratory failure on the 13th day of admission. An autopsy, performed 2 h after death, revealed a perianal tumor with pseudoalveolar growth pattern. In the lungs, a relatively large number of small metastatic foci, presumed to be lymphatic spread, were identified. It was diagnosed as PLS due to alveolar RMS. Although PLS is reported to be an unexpected form of metastasis, it might cause severe dyspnea in patients with RMS, as 4 of 18 reported cases of PLS are associated with RMS.

Large cell neuroendocrine carcinoma (LCNEC) of the ureter is an extremely rare entity. Herein, we present a case of primary LCNEC of the distal ureter in an 80-year-old male with a history of intermittent hematuria and a mass in the right distal ureter on computed tomography of the abdomen and pelvis. The patient subsequently underwent surgery followed by adjuvant chemotherapy. Histology and immunohistochemistry were in accordance with LCNEC.

Anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC) is a provisional renal cell carcinoma subtype with a growing list of published fusion partners. VCL-ALK gene fusion represents an uncommon fusion partner (only 6 reported cases), almost always associated with sickle cell trait and typically in a pediatric population. Herein, we report only the second case of VCL-ALK gene fusion ALK-RCC from a 31-year-old female without associated sickle cell trait, and also only the third reported case occurring in an adult patient. The tumor (measuring 8.5 cm and confined to the kidney) demonstrated mostly solid growth, pleomorphic nuclei, variably rhabdoid to vacuolated cytoplasm, and showed diffuse strong immunoreactivity for both PAX8 and ALK stains. Gene panel sequencing confirmed VCL-ALK gene fusion in the tumor. This study expands the clinical framework for diagnostic consideration of this rare tumor with potential targeted pharmacotherapy.

Fibrin- associated diffuse large B cell lymphoma (FA-DLBCL) is a rare entity, often incidental finding, categorized under “diffuse large B cell lymphoma associated with chronic inflammation (DLBCL-CI)“ in 2017 World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues. Here we report a 48-year-old male with FA-DLBCL who experienced recurrence within one year from initial presentation. The patient had a history of an abdominal aortic aneurism and underwent an endovascular aneurysm repair (EVAR) in 2013. Later in 2019, he was found by CT aortogram to have endoleak of the aneurysm repair. He underwent an open abdominal aortic aneurysm repair with explant of the endovascular stent. The explanted graft was sent to pathology and was found on gross examination to have ample adherent tissue. On microscopic examination this tissue was composed of abundant fibrinous material with several foci of large pleomorphic lymphocytes with enlarged round to polyhedral nuclei, prominent nucleoli, open chromatin, and scanty cytoplasm. Necrosis was also seen in a largest focus of tumor infiltrate. By immunohistochemistry, the atypical, large lymphocytes expressed CD20 and MUM-1; and positive for EBV, by Epstein-Barr virus (EBV) in situ hybridization (EBER-ISH). Together, the diagnosis for FA-DLBCL was made. Further work up by PET scan showed no active disease. The patient re-presented 10 months later with right lower extremity ischemia due to the vascular graft thrombosis. The thrombectomy specimen showed identical findings of his initial FA- DLBCL. Here we discuss the clinicopathologic findings of this entity and the importance of clinical follow up.

Xanthogranulomatous inflammation of the female genital tract is a rare entity with less than thirty cases being previously reported in the literature. It is characterized by destruction of the normal tissue followed by replacement with inflammatory cells and lipid- laden macrophages. In this report, we present a 55-year-old African American female with history of diverticulosis and use of intrauterine device, who presented with xanthogranulomatous inflammation extensively involving the fallopian tubes and ovaries, and concomitant diverticular perforation.

We report a case of high-grade endometrial stromal sarcoma originally assumed to be a benign leiomyoma, with BCOR internal tandem duplicates resulting in BCOR overexpression. A 34-year-old female presented to the gynecologic oncology service for recent miscarriage attributed to a large leiomyoma. She reported symptoms of vaginal bleeding and abdominal pain. Myomectomy and tissue analysis was performed which revealed BCOR internal tandem duplicates and cyclin D1 positive high grade endometrial sarcoma. Definitive treatment for the sarcoma was performed with pelvic washings, robotic assisted total laparoscopic hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and pelvic lymph nodes dissection. Negative margins were obtained along with negative lymph node and omental sections. Her sarcoma was staged pT1b (FIGO 1B). At follow up, patient reported no symptoms and was informed no further treatment was indicated. It is rare for high grade endometrial stromal sarcoma (HG-ESS) to present in a 34-year-old woman, though BCOR internal tandem duplicate (ITD) high grade endometrial stromal sarcoma is more common in younger women. This patient also had a unique finding in the pathology report, positive progesterone receptor (PR) expression, making this an interesting but difficult diagnosis.

We report a rare case of sclerosing epithelioid fibrosarcoma (SEF) arising in the anterior mandible of a 49-year-old male confirmed by the detection of an EWSR1-CREB3L3 fusion gene. SEF of the oral cavity is rare. To our knowledge this case marks the twelfth reported case to date. Our report and review of the literature highlights the molecular, immunophenotypic, and unique clinicopathological features of SEF in the oral cavity, specifically, its predilection for the jaw bones. Although SEF is usually a malignancy of soft tissue, nine (75%) of the reported oral cavity cases have occurred as a primary jaw neoplasm. The mandible represents the most common location with seven cases, while two occurred in the maxilla. These findings suggest a propensity for bone involvement in the oral cavity, which may be a feature unique to this site.

This report describes a 70-year-old male with bilateral primary adrenal lymphoma (PAL) characterized as non-germinal center diffuse large B-cell lymphoma (DLBCL). PAL is a very rare, aggressive disease with a poor prognosis. Our patient presented with B symptoms, chills, and nausea. Imaging studies of his abdomen revealed rapidly enlarging bilateral adrenal masses. Computed tomography (CT) guided left adrenal mass core biopsy showed diffuse sheets of neoplastic cells with irregular nuclear contours, vesicular to hyperchromatic chromatin, and prominent nucleoli. The neoplastic cells demonstrated an immunohistochemistry (IHC) profile consistent with DLBCL. Markers assessing for melanoma and neuroendocrine tumors were negative. Fluorescence in situ hybridization (FISH) revealed BCL6 rearrangement. The diagnosis of primary adrenal DLBCL, non-germinal center subtype, was rendered. The patient’s chemotherapy is ongoing; six cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) induced significant clinical and radiological response. The differential diagnosis is broad in patients with adrenal insufficiency and bilateral adrenal masses, and our case clinically centered on metastatic melanoma in the differential. Thorough pathologic evaluation of tissue, including an extensive IHC panel, was warranted for this patient due to the rarity of PAL and due to the morphologic overlap between melanoma and DLBCL.

• MPM could present with an unexpected immunophenotype – a strong CK20 positivity. • MPM with EWSR1-ATF1 fusion is rare and associated with the BAP1 wild type. • Molecular study is essential to confirm MPM with EWSR1-ATF1 fusion and positive CK20. Malignant peritoneal mesothelioma (MPM) is a rare, aggressive, and fatal neoplasm of the abdominal mesothelium with a very abysmal survival if left untreated. MPM with EWSR1-ATF1 fusion is an uncommon entity recently recognized by molecular studies. We report the first case of MPM with EWSR1-ATF1 fusion and aberrant CK20 expression. The patient was a 38-year-old man who presented to our institution with three months history of abdominal pain and distention, a significant weight loss (>30 lb), and failure to thrive. He was working in a construction company with 20 year-history of questionable asbestos exposure. Imaging studies demonstrated radiographic patterns suggestive of extensive peritoneal carcinomatosis. However, serum tumor markers were within the normal limit (CA 19–9, CEA, AFP, and βHCG). Subsequently, he underwent a biopsy of the peritoneal nodules. Biopsy showed a proliferation of epithelioid/round cells with ample cytoplasm and occasional vacuoles, displaying papillary architecture. Immunohistochemistry showed tumor cells were strongly and diffusely positive for WT1, AE1/3, CK7, CK20, desmin, and CD99, focally positive for calretinin, D2-40, and CK5/6, while negative for BerEp4, MOC-31, trypsin, TTF-1, P40, GATA3, CDX2, and PAX8. P16 and BAP1 were retained. Fluorescence in situ hybridization studies showed EWSR1 rearrangement, and the NGS fusion panel revealed EWSR1-ATF1 fusion. A diagnosis of MPM with EWSR1-ATF1 fusion was rendered. Unfortunately, the patient passed away within a month of diagnosis. Pathologists should be aware of this entity, especially when faced with tumors displaying mesothelioma morphology but showing atypical immunoprofile (co-expression of mesothelial markers with strong CK20).

Conjoined twins occurred in one of every 58,000 births. Parapagus dicephalus tribrachius with a single heart is a scarce variant of conjoined twins. A male parapagus conjoined twins with tribrachius was born by cesarean section with severe asphyxia, weighing 3170 g from 25 years old mother with G1P0A0, 35–36 weeks gestation. There is one umbilical cord, and the placenta consists of 1 amnion, one chorion. The baby has a single heart, a pair of the lung, a single stomach, duodenum, liver, double columna vertebralis with the single pelvis, one penis, undescended right, and left testes, one anus, and a pair of inferior extremities. After 28 h of treatment, the patient's condition became unstable, deteriorated, and died. This case reminds us of the importance of antenatal care and ultrasound examination since early pregnancy.

• Renal EWS is rare, with aggressive clinical progression, early metastasis and poor prognosis. • Combination of histological and immunohistochemical evaluation is important for the diagnosis. • Renal mass with vessel and/or spinal invasion should raise suspicion for renal EWS. In this report, we present a rare case of renal EWS in a 47-year- old man who presented with complaints of hematuria and flank pain. On CT imaging a 7 cm lobulated mass was discovered. Suspecting malignancy, a radical nephrectomy was performed. Microscopic evaluation showed features consistent with a small round blue cell sarcoma. Immunohistochemical stains and FISH with positive EWSR1 translocation confirmed the diagnosis. An extensive review of literature in English language returned under 150 reports of renal EWS making it a rare entity with many differentials like rhabdomyosarcoma, neuroblastoma and desmoplastic small round cell tumor.

Acinar cell carcinoma (ACC) is a rare form of pancreatic cancer that has been reported to occur in pancreatic heterotopia of the gastrointestinal tract. Molecular profiling studies of primary pancreatic ACC describe genetic alterations distinct from pancreatic adenocarcinoma. However, molecular testing in ACC arising from pancreatic heterotopia has not been described. We report a case of ACC of the stomach associated with pancreatic heterotopia in a 76-year-old man. The clinical, microscopic, immunohistochemical, and molecular features are described, including analysis via a targeted 225-gene next-generation sequencing (NGS) panel. Two novel mutations involving PIK3CA and AXIN1 are described, with implications for therapeutic options. This study is the first to characterize the molecular profile of ACC arising in pancreatic heterotopia and broadens the molecular landscape of these rare tumors.

Intravascular large B-cell lymphoma (IVLBCL) is a very rare type of extranodal large B-cell lymphoma that selectively grows within vessels and can spread to any organs or tissues. A very few cases of synchronicity with malignant tumor have yet been described. We report a rare case of IVLBCL accompanying a pleural malignant solitary fibrous tumor (MSFT). A 76-year-old man presented with a chronic dry cough, fever, minor general state deterioration and pancytopenia. Imaging revealed a large pleural mass. Histologically, the mass consisted of a MSFT. However, CD20 + malignant round cells were scattered within lumina of intratumoral blood vessels, evidencing a synchronous IVLBCL occurrence. Molecular analysis of the lymphoid clone identified MYD88 and CD79B gene mutations. After pleural mass excision, global health’s patient improved with cytopenia correction. However, a general state deterioration appeared 4 months after surgery, associated with a large retroperitoneal mass presenting the same pathological and molecular patterns identical to the initial IVLBCL clone.

Extranodal NK/T-cell lymphoma, nasal type, is an unusual Epstein-Barr Virus (EBV)-related lymphoma that carries a poor prognosis. Most cases affect upper aerodigestive tract, and secondarily may extend to skin, lungs, testis, and other sites. Extranodal NK/T-cell lymphoma, nasal type, presenting primarily as intestinal lymphoma is rare, and not recognized as a distinct entity and neither is considered as a special subtype of intestinal lymphoma of T-cell lineage. Here, we describe a 36-year-woman who presented with abdominal pain and acute-onset diarrhea. Her clinical course was complicated by intestinal perforation and peritonitis. She died one month later of sepsis. Pathologic examination revealed extranodal NK/T-cell lymphoma, nasal type, confined to the intestine. Immunophenotypically, the neoplastic cells expressed CD3 and Granzyme B, and were positive for EBV-encoded RNA (EBER) by in situ hybridization. From the practical point of view, we highlight the clinical, pathologic and immunophenotypic features that can be useful in the differential diagnosis from other intestinal lymphomas of T-cell lineage.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive genetic disorder in which the proper function of lysosome-related organelles (LROS) is impaired due to mutation in one of several well-characterized genes, including, but not limited to: HPS1, HPS3, and HPS4. Clinical manifestations include oculocutaneous albinism, nystagmus, platelet dysfunction, progressive pulmonary fibrosis, and granulomatous colitis. We present a case of a 28-year-old woman of Puerto Rican descent who required post-partum lung transplantation due to an inherited HPS1 mutation. The pathologies observed in HPS underline the mechanistic importance of LROS in a variety of tissue types and organ systems.

Sarcina Ventriculi is a gram-positive organism, rarely encountered as a human pathogen. It has been described in stomach specimens, often in patients with delayed gastric emptying. The exact role of this organism in human disease is not clear. In this case report, we describe a case of Sarcina organism associated with gastric ulceration. This organism is likely underreported and often overlooked, as it may not be obvious on routine staining. Awareness of this organism and further studies are needed to understand its role in human disease.

Mucinous carcinoma of breast is a rare variant of invasive breast carcinoma and usually affects older females and is associated with good prognosis. Human epidermal growth factor receptor 2 (HER2) positivity in these tumors is rare. We describe here a case of advanced stage HER2 + mucinous carcinoma with micropapillary features who underwent complete remission on treatment with radiation therapy and hormonal therapy and presented after eight years with invasive duct carcinoma in the contralateral breast.

Approximately 24 cases of cytokeratin-positive interstitial reticulum cell tumors have been reported in English literature. In this paper, we report a case of cytokeratin-positive interstitial reticulum cell tumor that was localized in the parafollicular region of the axillary lymph node and was an incidental finding in a patient with breast cancer. A 50 year-old woman underwent a mastectomy and lymph node dissection following a preoperative diagnosis of bilateral breast cancer. Histopathological examination revealed that the patient had non-invasive and invasive ductal carcinoma in the right and left mammary glands. Although we could not detect breast cancer metastasis in the lymph nodes, one of eight right axillary lymph nodes harbored an 11 × 8 mm discohesive sheet of large polygonal epithelioid tumor cells in the parafollicular area. Tumor cells were immunoreactive for AE1/AE3, CAM5.2, CK18 and l-caldesmon and negative for CD1a, CD21, CD23, CD31, CD68, and S‑100 protein markers. Based on these findings, the lesion was diagnosed as a cytokeratin-positive interstitial reticulum cell tumor of the lymph node. Notably, this early-stage cytokeratin-positive interstitial reticulum cell tumor demonstrated focal nuclear YAP/TAZ proto-oncogene products, which were recently identified as critical for differentiation, maturation, and function of fibroblastic reticular cells. To the best of our knowledge, this is the first report to describe nuclear YAP/TAZ immunoreactivity in cytokeratin-positive interstitial reticulum cell tumors.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor, which can be seen in varied anatomic locations, most commonly arising in the lung/pleura. SFTs of the gastrointestinal tract are exceedingly rare. Herein we report a case of SFT presenting as a 35 mm polyp in the descending colon, arising from the submucosa, that was found during routine screening colonoscopy in a 66 year old male. This was clinically felt to be a lipomatous lesion. Histologic sections demonstrated a spindle cell lesion with haphazard/patternless architecture, hyalinized collagen, and dilated, ectatic, irregularly shaped “staghorn” vessels. Mitoses were infrequent. Immmunostains demonstrated the neoplastic cells were positive for CD34 and STAT6; while they were negative for c-Kit, DOG1, SMA, and S100, confirming the diagnosis of SFT. The patient was disease free following the procedure. To our knowledge, this is only the second reported case of SFT presenting as a polyp, arising from the submucosal layer of the colon.

We report a case of a primary malignant solitary fibrous tumor (SFT) of the urinary bladder in a previously healthy 35-year-old male. The unusual presentation, focal GATA3 expression in the biopsy and the excessive rarity of the entity at the involved location all contributed to a challenging diagnosis, which was finalized with the resection specimen. Review of the literature highlighted the rarity of this tumor but revealed a relatively positive outcome, with no previous reports of disease recurrence. We therefore describe the first report of malignant bladder SFT associated with pulmonary metastases.

Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a newly accepted entity that belongs to the group of low-grade adipocytic neoplasms. ASPLT commonly manifests a soft tissue mass in both upper and lower extremities but is extremely rare in the gastrointestinal tract. Here we report a case of a gastric ASPLT in a 59-year-old male, who presented for the evaluation of new onset of dysphagia. To our best knowledge, this is the first case report of ASPLT in the upper gastrointestinal tract.

Sarcoidosis is a systemic idiopathic granulomatous disease that most commonly presents with lungs and hilar lymph node involvement. Clinical manifestation with acute ischemic stroke, with central neurological and cardiac involvement is extremely rare. Herein we report the case of a 60-year-old African American woman with history of chronic heart failure and pacemaker implantation, who presented with acute ischemic stroke, and died within 34 h of hospitalization. On autopsy, well-formed non-caseating granulomas were present in the myocardium, adventitia of the left main coronary artery, all lobes of bilateral lungs, pleura, liver, and spleen. The brain also showed granulomas, with predominantly leptomeningeal and focal parenchymal involvement of the central basal brain tissue (hypothalamic region), but without vascular wall involvement. Granulomas were also present within the thyroid as well as an incidental finding of a Hürthle-cell adenoma (HCA). We believe that left internal carotid artery and left middle cerebral artery obstruction, possibly thromoboembolic from the heart, was the cause of acute regional brain ischemia. This rare case illustrates the importance of the autopsy in the diagnosis of unexpected medical conditions; and also that sarcoidosis may play an etiologic role in acute ischemic stroke.