Metastatic prostate adenocarcinoma and high-grade appendiceal mucinous neoplasm mimicking acute appendicitis in a post-radiation therapy patient.

Prostate cancer is the most common visceral malignancy diagnosed in males. Surveillance for post-treatment neoplasms is very crucial. Here we report the first case of recurrent metastatic prostate cancer presenting as acute appendicitis in a background of a high-grade appendiceal mucinous neoplasm. In addition, this case also includes an unusually early presentation of a secondary primary malignancy after radiation therapy. A 70-year-old male with a history of prostate adenocarcinoma status post-proton radiation therapy presented with recurrent poorly differentiated prostate adenocarcinoma with disease progression and extra-prostatic extension. He underwent salvage proton therapy and testosterone replacement therapy. Two years later, the patient presented with right lower quadrant pain. A computed tomography scan showed perforated acute appendicitis with intra-abdominal abscess, which was treated with interval appendectomy. Upon histologic analysis, metastatic prostatic adenocarcinoma was noted in the appendiceal wall and mesoappendix. In addition, an incidental background of high-grade appendiceal mucinous neoplasm was found. Four months later, he presented with persistent abdominal pain, rapid weight loss, fatigue, and fever for 3 months. An abdominal CT scan revealed a 6.1 cm rectal mass. Pathologic analysis diagnosed an aggressive post-radiation spindle cell sarcoma, intermediate to high grade. The patient opted for palliative care. This case shows that a clinical presentation of acute appendicitis in an older patient may sometimes portend a neoplastic rather than infectious etiology. Clinical history and patient epidemiology should always be considered when evaluating an older patient with clinical signs and symptoms of acute appendicitis.

Recent Advances in Digestive Tract Tumors: Updates From the 5th Edition of the World Health Organization "Blue Book".

CONTEXT.­: The World Health Organization Classification of Tumours: Digestive System Tumors, 5th edition, was published in 2019 and shows several impactful changes as compared with the 4th edition published in 2010. Changes include a revised nomenclature of serrated lesions and revamping the classification of neuroendocrine neoplasms. Appendiceal goblet cell adenocarcinoma is heavily revised, and intrahepatic cholangiocarcinoma is split into 2 subtypes. New subtypes of colorectal carcinoma and hepatocellular carcinoma are described. Precursor lesions are emphasized with their own entries, and both dysplastic and invasive lesions are generally recommended to be graded using a 2-tier system. Hematolymphoid tumors, mesenchymal tumors, and genetic tumor syndromes each have their own sections in the 5th edition. New hematolymphoid lesions include monomorphic epitheliotropic intestinal T-cell lymphoma; duodenal-type follicular lymphoma; intestinal T-cell lymphoma, not otherwise specified; and indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. This paper will provide an in-depth look at the changes in the 5th edition as compared with the 4th edition. OBJECTIVE.­: To provide a comprehensive, in-depth update on the World Health Organization classification of digestive tumors, including changes to nomenclature, updated diagnostic criteria, and newly described entities. DATA SOURCES.­: The 5th edition of the World Health Organization Classification of Tumours: Digestive System Tumours, as well as the 4th edition. CONCLUSIONS.­: The World Health Organization has made many key changes in its newest update on tumors of the digestive system. Pathologists should be aware of these changes and incorporate them into their practice as able or necessary.

Severe chronic bowel obstruction associated with brown bowel syndrome.

A 61-year-old alcoholic male with history of cholecystectomy presented with a 20-year history of recurrent bowel obstruction and a 30 lb weight loss. After numerous attempts at conservative management, exploratory laparotomy was performed, which showed no mechanical cause. Despite no clear etiology, the obstruction persisted and intensified. A follow-up computed tomography scan revealed a small bowel obstruction with concurrent megacolon. A total abdominal colectomy was performed, with ileostomy. Grossly, there was intestinal dilation up to 15 cm with prominent brown discoloration of bowel wall. No strictures or other fixed obstruction were identified. Microscopic examination revealed prominent lipofuscin-like pigment deposition, involving the muscularis propria, muscularis mucosae, and vascular smooth muscle. Histochemical staining was positive for periodic acid-Schiff and negative for iron and calcium, consistent with lipofuscin. The gross and histologic findings fit with brown bowel syndrome. Brown bowel syndrome is a very rare condition characterized by lipofuscin deposits predominantly within the smooth muscle of the muscularis mucosae and/or muscularis propria that imparts a brown color to the bowel. It is generally thought to be a smooth muscle mitochondrial myopathy due to chronic vitamin E deficiency secondary to fat malabsorption syndromes, resulting in free radicals causing peroxidation of unsaturated membrane lipids with accumulation of lipofuscin. Brown bowel syndrome may be seen in patients with alcohol abuse, maldigestion, chronic bowel inflammation, and intestinal lymphangiectasia. Our patient's severe chronic intestinal pseudo-obstruction, low levels of certain fat-soluble vitamins (A, D, and E), significant weight loss and history of cholecystectomy with alcohol abuse correlates with brown bowel syndrome clinically.

Regional Lymph Node Enlargement in Clinically Severe Cherubism.

Cherubism is a rare benign autosomal dominant disorder characterized by progressive, painless, bilateral enlargement of the mandible and/or maxilla because of bone replacement by fibrotic stromal cells and osteoclast-like cells forming multilocular cysts. The lesions typically stabilize and regress after puberty. We present a 14-year-old male with severe familial cherubism. Bilateral mandibular enlargement began around age 4 and progressed until puberty, affecting his speech and mastication without subsequent involution. Composite mandibulectomy and mandible reconstruction with fibula free flap technique improved functionality and cosmesis. Histology was consistent with the diagnosis of cherubism, showing large areas of bland spindle-cell fibrous tissue and moderately abundant collagen and multiple nodules of giant cell-rich tissue resembling central giant cell granuloma. Regional lymph nodes were sampled due to enlargement, demonstrating hemosiderin-laden macrophages and basophilic laminated concretions localized to the cortical interfollicular space and along the peripheral follicular marginal zone, findings which have not been previously reported.

Propionibacterium acnes-associated neurosarcoidosis: A case report with review of the literature.

A 56-year-old woman with a 3-year history of hydrocephalus and ventriculo-peritoneal shunt placement, presented with worsening altered level of consciousness for 2 days. Imaging studies showed severe ventriculomegaly involving the lateral and third ventricles with multiple septated cysts noted in the lateral ventricles predominantly near the frontal horns. Histopathologic examination of the excised brain lesion revealed choroid plexus tissue and adjacent cerebral parenchyma with several non-caseating granulomas. Granulomatous inflammation was also identified in mediastinal lymph nodes. By using specific monoclonal antibodies, Propionibacterium acnes (P. acnes) were detected in non-caseating granulomas of both the brain and mediastinal lymph nodes. No acid-fast bacilli or fungal elements were present. To the best of our knowledge, this is the first demonstration of P. acnes in sarcoid granulomas of cerebral tissue, and it reinforces the possible link between P. acnes and sarcoidosis.

EBV-associated hepatic smooth muscle tumor of uncertain biologic behavior after heart transplantation in a pediatric patient: case report.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare neoplasm recognized in immunocompromised patients. There are less than 30 cases of EBV-SMT reported in pediatric population following solid organ transplantation. Herein, we report a case of an 8-year-old female who was incidentally noted to have multiple lesions in the liver 8 years after heart transplantation. The tumor was composed of a cellular proliferation of spindle-shaped cells with low mitotic activity. The diagnosis of EBV-SMT was confirmed by in situ hybridization for EBV-encoded small RNA (EBER) transcripts. Multiple additional lesions were detected by whole body positron emission tomography-computed tomography (PET-CT) scan 4 months after the initial finding of the hepatic lesions. Immunosuppression was switched to a mechanistic target of rapamycin (mTOR) inhibitor. We conclude that EBV-SMT should be included in the differential diagnoses in post-transplantation patients and further investigations should be performed to evaluate additional lesions.

Primary B-cell lymphoma of the uterine cervix: Presentation in Pap-test slide and cervical biopsy.

This case involved a 69-year-old female who presented with irritative urinary voiding. Imaging studies showed an 18-cm uterine mass centering on the cervix and extending into the bladder. The Pap test slide demonstrated necrotic background and degenerative changes in single and grouped atypical "small round blue cells" with high nuclear/cytoplasm ratio, scant cytoplasm, and hyperchromatic focally cleaved nuclei with occasional nuclear membrane "snout projections." Cervical biopsies showed similar findings. The tumor cells were positive for CD45, CD20, and PAX-5, and negative with epithelial, neuroendocrine, and muscle markers. A Ki-67 immunostain showed a markedly elevated proliferative index and the MUM1 stain was diffusely positive. Molecular study identified clonal immunoglobulin heavy chain gene rearrangement. Owing to its rarity, cervical lymphoma may sometimes be confused with other types of malignant neoplasms or inflammatory processes. Therefore, it is important to recognize the cytological features of cervical lymphomas and be aware of the potential diagnostic pitfalls for timely diagnosis and therapy. Diagn. Cytopathol. 2017;45:235-238. © 2016 Wiley Periodicals, Inc.

Undifferentiated embryonal sarcoma of the liver with an unusual presentation: case report and review of the literature.

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant mesenchymal neoplasm, relatively unique to the liver that occurs primarily in children and teenagers. Delay in diagnosis is not uncommon due to lack of a characteristic clinical presentation, serological markers and radiological changes. We report a case of UESL in a 9-year-old girl who presented with right upper quadrant pain and a palpable mass. Laboratory and imaging workup revealed a complex hepatic cyst, increased IgE, transient peripheral eosinophilia and a normal alpha-fetoprotein (AFP). Initial empirical treatment with albendazole was implemented for presumed hydatid cyst disease, but the child failed to improve. Subsequent surgical resection resulted in the correct diagnosis of UESL. She received 6 months of chemotherapy and remains well with no evidence of tumor about 12 months after resection. We herein review the typical clinical, radiologic and pathologic features of this rare tumor.

Consensus and conflict in invasive micropapillary carcinoma: a case report and review of the literature.

Invasive micropapillary carcinoma (IMPC) is an aggressive histologic subtype of adenocarcinoma that has been gaining increased attention over the past twenty years. It is important to recognize IMPC due to its strong association with early lymphovascular invasion (LVI), high risk of lymph node metastasis, perineural invasion and poor prognosis. Controversies regarding IMPC include differentiating from retraction artifact and mimics, clinical significance of proportion of micropapillary component (MC), pathogenesis, biologic nature of the entity and consequently terminology, etc. We herein present a case of rectal IMPC arising from a tubulovillous adenoma. Since HER2 over-expression has been reported in IMPC of the breast and the bladder but never in the colorectum, given the availability of HER2 targeted therapy, HER2 protein expression in our case is examined by immunohistochemical study which shows weak incomplete membrane staining in less than 5% of cells. Literature is reviewed with emphasis on colorectal IMPC as well as aforementioned controversial topics. In summary, more study is needed to resolve the conflicts and build consensus on IMPC.

Pyloric gland adenoma of gallbladder-reports of two cases and a brief review of literature.

Adenomas of the gallbladder are uncommon benign epithelial neoplasms. Rarely, they can give rise to gallbladder cancer, which is the most common malignancy of the biliary tract, carrying a poor prognosis and decreased survival. Here we report the case histories of two patients, 40-year-old and 53-year-old males who presented with >1 cm gallbladder polyps, which were detected and confirmed using various imaging studies. Cholecystectomy was performed on both patients and the subsequent pathologic exam revealed 1.2 and 1.6 cm polyps in the lumen. Histopathologically, both polyps showed features reminiscent of "pyloric" gland type of adenoma. The differences between the two cases in regard to histopathological and immunohistochemical characteristics will be discussed. We will also briefly review the latest nomenclature on such low-grade polypoid gallbladder entities.

Non-pancreatic retroperitoneal mucinous neoplasms and a discussion of the differential diagnosis.

Retroperitoneal mucinous neoplasms are common and have a wide range of differential diagnoses to consider. It is of utmost importance to maintain a multidisciplinary approach when evaluating these lesions. Clinical history, surgical impression and radiographic studies should be obtained and used in conjunction with morphology and immunohistochemistry to help guide the pathologist to the correct diagnosis. We recently encountered a case of a 51-year-old man who presented with an 11.5 cm left-sided retroperitoneal mucinous neoplasm. This lesion was initially diagnosed as a low-grade mucinous carcinoma of probable pancreatic origin at an outside facility, and he was subsequently treated with chemotherapy. One year later he presented to our institution and underwent retroperitoneal en bloc resection of the 7-cm residual multiloculated mucinous neoplasm. When discussed at tumor board additional medical history was obtained, and review of the patient's chart revealed a remote history of left orchiectomy for a mixed malignant germ cell tumor and metastatic embryonal carcinoma in 2 of 34 retroperitoneal/para-aortic lymph nodes. With no clinical evidence of tumor in the pancreas or extension from it, the predominately para-aortic location of the tumor favors a mucinous carcinoma arising from a rest of mature metastatic/proliferating teratoma that persisted after chemotherapy. This case illustrates the importance of a thorough history, however remote, and correlation with imaging in the development of differential diagnoses, as well as, the need to consider non-pancreaticobiliary sources of retroperitoneal mucinous tumors.

Coexistence of intestinal Kaposi sarcoma and plasmablastic lymphoma in an HIV/AIDS patient: case report and review of the literature.

Human immunodeficiency virus (HIV) infection or acquired immunodeficiency disease (AIDS) is associated with increased risk for various malignancies including Kaposi sarcoma (KS) and lymphoma. We report a rare case of coexistence of KS and plasmablastic lymphoma (PBL) in the gastrointestinal (GI) tract in a HIV/AIDS patient. A brief review of literature is also presented.

Nuclear protein in testis midline carcinoma with unusual elevation of α-fetoprotein and synaptophysin positivity: a case report and review of the literature.

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare cancer that displays a characteristic chromosomal rearrangement of BRD4-NUT t(15;19)(q14;q13.1). Despite occasional dramatic responses to radiation and chemotherapy, NMC usually behaves aggressively and becomes rapidly progressive. Immunohistochemical staining is usually limited to p63, cytokeratins, and monoclonal NUT antibody. Here, we report a NMC case in a 36-year-old man with elevated serum α-fetoprotein (AFP), synaptophysin positivity, and a 9.0 cm mass involving the right lung and mediastinum. Tumor cells demonstrated BRD4-NUT fusion on fluorescence in situ hybridization. To our knowledge, only one other case with elevated serum AFP and one case with synaptophysin positivity have been described. This diagnosis will undoubtedly grow more common as informed physicians become more aware of the disease and begin testing for NMC. Further study is needed to establish the prevalence of NMC and to elucidate the significance of elevated AFP and synaptophysin positivity in this rare tumor.

Cytoplasmic vacuoles: clue in the fine-needle aspiration diagnosis of melanoma.

For the fine-needle aspiration (FNA) diagnosis of melanoma recognition of characteristic morphologic features is key. In our practice we noted that cytoplasmic vacuoles in Romanowsky-stained FNA smears of melanoma appeared to be a frequent finding. To investigate this premise, we examined 36 consecutive melanoma FNA cases that had both adequate Papanicolaou-stained and Romanowsky-stained smears in an effort to determine the prevalence, and thereby, the potential diagnostic utility of cytoplasmic vacuoles in the diagnosis of melanoma compared to established cytomorphologic parameters of melanoma. We found pigment in 21 cases (58%) and plasmacytoid cells in 28 cases (78%), and in all 36 cases (100%) we found bi/multinucleation, intranuclear cytoplasmic inclusions and prominent nucleoli. Cytoplasmic vacuoles were present in 30 cases (83%) and were found in air-dried Romanowsky-stained smears only. These findings suggest that in FNA smears of melanoma cytoplasmic vacuoles in Romanowsky-stained smears have prevalence and potential diagnostic utility that are comparable to widely recognized cytomorphologic features of melanoma. Numerous articles have focused on the cytomorphologic criteria for the FNA diagnosis of melanoma, but few have noted the presence of cytoplasmic vacuoles in FNA smears of melanoma, and rare reports suggest this finding to be a useful clue to the FNA diagnosis of melanoma. This report appears to be the first to focus on the prevalence and potential diagnostic utility of cytoplasmic vacuoles in FNA samples of melanoma.

Cytopathology of the pancreatobiliary tract-the agony, and sometimes, the ease of it.

Pancreatic cytopathology is recognized as a rapid, reliable, safe and cost-beneficial modality of investigation of pancreatic mass lesions. Optimal cytodiagnosis depends on multiple factors including sample quality, and expertise of the cytopathologist and endoscopist. This article discusses key cytologic features of specific tumor types, specimen handling, differential diagnoses and pitfalls.

Cytopathologic diagnosis of liver mass lesions.

The liver is a common site for metastatic malignancies, particularly from the gastrointestinal tract. It also may be involved by primary neoplasms, both benign and malignant. Cytopathologic examination of mass lesions of the liver with pertinent use of ancillary studies is a useful method of establishing a correct diagnosis for patient management. The authors reviewed the literature for articles pertaining to cytologic characteristics of specific tumor types, utility of immunohistochemical markers and pertinent molecular studies, differential diagnoses and pitfalls.

Parotid dermoid cyst: a case report.

A dermoid cyst arising in the parotid is rare and usually represents the rare first branchial cleft type II anomaly, which can have morphology similar to a dermoid cyst. This study reports the case of a 20-year-old woman who presented with a parotid mass, which on histologic review was consistent with a dermoid cyst. This appears to be the first case report of a parotid dermoid cyst with focus on the gross and histopathologic findings and to be presented in a histopathology focused journal. The discussion includes the clinical presentation, imaging findings, gross pathology, histologic features, and differential diagnosis of parotid dermoid cysts. Although there was no prior fine needle aspiration (FNA) of the lesion in this case, parotid masses are commonly subject to FNA prior to excision. Therefore, a brief review of the FNA findings in dermoid cysts is also included.

Role of cytopathology in the diagnosis and management of gastrointestinal tract cancers.

Cytology of gastro-intestinal (GI) tract lesions can be used successfully to diagnose neoplastic and non-neoplastic conditions, especially when combined with biopsies. Cytologic evaluation is widely accepted as a cost-effective method that allows rapid interpretation and triaging of material. Technical advances over the years have allowed simultaneous visualization of abnormal tissue and procurement of needle aspirates, brushings and biopsies from mucosal and deeper seated lesions. Successful cytologic examination of the GI tract is highly dependent on the skill of the endoscopist, specimen preparation, the expertise of the pathologist, and the recognition of the limitations of cytology. This article reviews the key cytologic features of important GI tract lesions, differential diagnoses, and pitfalls, and addresses the advantages and limitations of different collection techniques.

Pigmented villonodular synovitis: extrasynovial recurrence.

A 32-year-old female athlete underwent arthroscopy for a second recurrence of pigmented villonodular synovitis (PVNS), which was extrasynovial, seen on magnetic resonance imaging. It was noted on arthroscopy that (1) the nodules moved medially with joint insufflation, (2) the nodules were less prominent than on magnetic resonance imaging, and (3) more than 95% of the recurrent tumor was hidden by neosynovium. We believe that the extrasynovial location is because of the more rapid proliferation of the neosynovium relative to the growth of the remaining tumor cells after the previous resection. In resecting pigmented villonodular synovitis with a high risk of recurrence, a layer of periarticular fat should be removed and the surgeon should be wary of change in position with insufflation.

CD34, CD117, and Ki-67 expression in phyllodes tumor of the breast: an immunohistochemical study of 33 cases.

Phyllodes tumors (PTs) of the breast are biphasic lesions, comprising an epithelial component set within a neoplastic spindle-celled stroma. These tumors have been classified as benign, borderline, and malignant based on a combination of histological criteria, including stromal cellularity, nuclear pleomorphism, mitotic rate, stromal overgrowth, and margin appearance. The aim of this study was to evaluate the expression of CD34, CD117 (c-kit), and Ki-67 in PT of the breast and attempt to correlate the staining pattern with tumor grade by morphology. Immunohistochemical expression of CD117, CD34, and Ki-67 was studied on formalin-fixed, paraffin-embedded archival tissue material from 33 cases of PT. Histologically, there were 21 benign, 6 borderline, and 6 malignant (high-grade) tumors. All 6 histologically malignant PTs were positive for CD117 (100%), but only 1 marked with CD34 (16.7%). Borderline PTs frequently coexpressed CD34 and CD117 (66.7%). The benign PTs, on the other hand, most commonly (52.4%) showed a CD34(+)/CD117(-) immunoprofile with 33.3% cases coexpressing the markers: that is, CD34(+)/CD117(+). Although most benign PTs (80.6%) showed a Ki-67 of <2%, a few cases showed slightly higher proliferation indices. This study indicates that CD34 and CD117 are differentially expressed in benign and malignant PTs. These markers, therefore, in combination, may be used as an adjunct to morphology in the subclassification of PTs.