Jaclyn F. Hechtman

Promyelocytic leukemia zinc finger and histone H1.5 differentially stain low- and high-grade pulmonary neuroendocrine tumors: a pilot immunohistochemical study

Promyelocytic leukemia zinc finger is a zinc finger transcription factor that functions as a transcriptional repressor. Its expression has been shown to be down-regulated in hematopoietic, melanocytic, and mesothelial malignancies. Histone H1.5 is a variant of histone H1, a family of linker proteins that organizes chromosomes into higher order structures. Its function is of key importance in gene expression and has been linked to more aggressive forms of prostatic carcinoma. This study aimed to investigate the immunohistochemical detectability of promyelocytic leukemia zinc finger and histone H1.5 in pulmonary neuroendocrine tumors, comprising 11 carcinoid tumorlets, 24 typical carcinoids, 12 atypical carcinoids, 20 small cell carcinomas, 11 large cell neuroendocrine carcinomas, and 2 combined small cell carcinomas-large cell neuroendocrine carcinomas. Promyelocytic leukemia zinc finger immunohistochemistry revealed moderate or strong nuclear staining in all carcinoid tumorlets, 23 of 24 typical carcinoids, and 7 of 12 atypical carcinoids in contrast to 9 of 11 large cell neuroendocrine carcinomas, all small cell carcinoma, and both combined small cell carcinoma-large cell neuroendocrine carcinomas, which showed no nuclear immunoreactivity. Histone H1.5 immunohistochemistry revealed only focal or no immunoreactivity in all carcinoid tumorlets and 19 of 24 typical carcinoids, whereas 7 of 12 atypical carcinoids, 19 of 20 small cell carcinomas, 10 of 11 large cell neuroendocrine carcinomas, and both combined small cell carcinomas-large cell neuroendocrine carcinomas displayed positive (≥ 10%) nuclear immunoreactivity-ranging from a minority of weak staining to a majority of strong staining cases. Our data suggest that the relative expression ratios of promyelocytic leukemia zinc finger and histone H1.5 may correlate with grade of pulmonary neuroendocrine tumors. Immunohistochemical stains for these markers, especially on small biopsies with crush artifact, may prove to be diagnostically useful.

Intramuscular corpora amylacea adjacent to ileal low-grade neuroendocrine tumours (typical carcinoids): a light microscopic, immunohistochemical and ultrastructural study

Aims The purposes of this study are to (1) document the prevalence of intracytoplasmic inclusions adjacent to ileal well-differentiated neuroendocrine tumours (WNETs), (2) examine whether and how tumour and patient characteristics are associated with inclusions and (3) investigate their properties on special stains and electron microscopy in comparison with corpora amylacea (CA). Methods We examined the resection slides from 26 ileal, 5 gastric and 5 rectal cases of WNET. Inclusions were readily identified with H&E staining. Histochemical, immunohistochemical and ultrastructural evaluations were performed on the block with the highest number of inclusions. Results Intracytoplasmic inclusions occurred adjacent (<1u2005mm) to 15 of 26 (57.7%) ileal WNETs. Patients with and without inclusions were of similar mean ages (59.5 vs 57.4u2005years; p=0.88), but NETs with inclusions were larger than those without inclusions (3.3 vs 1.7u2005cm, p=0.03). Inclusions were neither associated with gastric (mean age=65u2005years, mean diameter=1.5u2005cm) or rectal WNETs (mean age=47.8u2005years, mean diameter=0.5u2005cm) (p=0.01), nor were they present >1u2005mm from ileal NETs. CA stained strongly for ubiquitin, DPAS and Alcian blue; faintly and peripherally for desmin and smooth muscle actin and negatively for calcium. Ultrastructurally, their appearance was consistent with filaments, some with cores of particle matter. Conclusions Our results suggest that these inclusions are virtually identical to CA and present adjacent to the majority of ileal WNET. They may be the result of a degenerative process, possibly due to chronic myocyte stress from an infiltrating slow growing tumour mass or local hormonal effects.

Mycobacterial pseudotumor of the plantar fascia: how common is it?

Mycobacterial spindle cell pseudotumor (MSCP) is an extremely rare complication of mycobacterial infections. It has been reported to occur in various sites such as skin, lymph nodes, bone marrow, lungs, and spleen. This tumor-like lesion can be confused clinically as well as radiographically with dermatofibroma, nodular fasciitis, xanthogranuloma, and Kaposis sarcoma. While this lesion is rare and has been previously reported to occur only in superficial skin, we emphasize its consideration and inclusion in the differential diagnoses when a deep soft tissue mass is complicated by symptoms of deep tissue infection secondary to abscess formation in immunocompromised hosts. Here, we present the clinical and radiologic findings of a case of MSCP involving the deep plantar sheaths.

Anti-Glutamate Receptor 2 as a New Potential Diagnostic Probe for Prostatic Adenocarcinoma: A Pilot Immunohistochemical Study

Diagnoses of prostatic carcinoma (PC) have increased with widespread screening. While the use of &agr;-methylacyl coA racemase and high molecular weight cytokeratins have aided in distinguishing benign mimics from malignancy, their sensitivity and specificity are limited. We studied 6C4, a monoclonal antibody to glutamate receptor 2, an excitatory amino acid receptor subunit distributed throughout the central nervous system, on benign prostatic epithelium, high-grade prostatic intraepithelial neoplasia, and PC. Ten cases with post-atrophic or adenosis-like prostate glands were also stained with prostatic intraepithelial neoplasia 4, an immunostain cocktail against &agr;-methylacyl coA racemase, p63, and high molecular weight cytokeratin, in parallel with 6C4. Immunoreactivity for 6C4 was graded as negative (0% to 10%), +1 (11%% to 50%), and +2 (>50%). Malignant epithelium was classified by Gleason patterns. Gleason patterns 4 and 5 were subdivided into cribriform or noncribriform type. Its utility in distinguishing postatrophic or adenosis-like glands from prostate cancer, both of which show absence of basal cells on prostatic intraepithelial neoplasia 4 immunostain, was also investigated. Our results revealed a statistically significant difference in staining of benign secretory prostatic epithelium, high-grade prostatic intraepithelial neoplasia, and low Gleason pattern carcinomas. The results also showed 6C4 is a sensitive marker in separating basal cell negative postatrophic or adenosis-like glands from prostate carcinoma. In addition, there was a statistically significant difference between staining of cribriform versus noncribriform Gleason pattern 4 and 5 carcinomas. A limited number of lymph node metastases from cribriform and noncribriform carcinomas were studied, and they stained the same as the primary tumor in the majority of cases. In conclusion, our preliminary data demonstrated potential utility of 6C4 in the pathologic evaluation of PC.

Neurogenic Polyps of the Gastrointestinal Tract: A Clinicopathologic Review With Emphasis on Differential Diagnosis and Syndromic Associations

Primary neurogenic gastrointestinal polyps are encountered relatively frequently in routine pathology practice. They encompass a variety of neoplastic entities with clinical, morphologic, and molecular features that reflect the diversity of neural elements within the gastrointestinal system. Although most are benign and encountered incidentally, accurate diagnosis may have important clinical implications because of the associations of certain neurogenic polyps with familial syndromes or other conditions. We review the pathology of these polyps with an emphasis on the diagnostic challenges that they pose and on newly described subtypes.

Thymomas diagnosed during pregnancy: two cases in young women without paraneoplastic or autoimmune disease

We report 2 cases of thymomas diagnosed during pregnancy. Neither of these 2 patients had paraneoplastic autoimmune conditions or previous neoplasia. The first patient had a 7.3-cm lymphocyte-predominant thymoma with capsular invasion. The second patient was diagnosed through fine needle aspiration biopsy after computed tomography showed multiple mediastinal masses. Although cases of thymoma during pregnancy have been reported, the exact cause has yet to be elucidated. We review the clinical, radiologic, pathologic, and immunohistochemical findings-including those of podoplanin, estrogen receptor, and progesterone receptor-of 2 previously unreported cases, as well as discuss the relationship of malignancy and pregnancy and review the available literature regarding pregnancy and thymoma.

Ischemic bowel due to embolization from an isolated mobile thrombus of the ascending aorta: a case report and review of the literature

Aortic thrombi are commonly present in atherosclerotic and aneurysmatic aortas. Thrombus formation in an aorta with or focal atherosclerosis in a patient without risk factors is rare. A 63-year-old woman with dementia and hypothyroidism presented with hypotension and respiratory distress. Work-up revealed leukocytosis, sinus tachycardia, and proximal small bowel obstruction. At emergent laparotomy, a superior mesenteric artery thomboembolus was identified with necrosis of surrounding bowel. The patient expired on hospital day five. Autopsy revealed a 1.4xa0cm thrombus overlying an isolated atherosclerotic plaque in the ascending aorta and infarctions of the spleen, liver, and right kidney as well as occlusive thromboembolism of the superior mesenteric artery. This case report illustrates lethal complications from an unsuspected aortic thrombus. Work-up for patients presenting with signs of peripheral embolization, or in this case, necrotic bowel, should include the aorta as a source of embolic thrombi.

Corpora amylacea in gastrointestinal leiomyomas: a clinical, light microscopic, ultrastructural and immunohistochemical study with comparison to hyaline globules

Context Corpora amylacea (CA) are inclusions with starch-like composition that occur in various conditions. We have observed CA in gastrointestinal leiomyomas (GILM) and hypothesised that they differ from intracytoplasmic hyaline globules (HG) of GILM. We aimed to investigate the anatomical distribution, prevalence, staining characteristics and ultrastructural features of CA and compare them with HG of GILM. Design Slides from a consecutive series of resected GILM and bland spindle cell tumours were examined for CA and HG. Special stains, electron microscopy and elemental analysis were performed on select leiomyomas. Results CA occurred in 13/35 GILM (37%) from the following sites: oesophagus (4/8), stomach (5/7) including one frozen section, small intestine (1/2) and large intestine (3/18), but were not identified in 19 gastrointestinal stromal tumours (12 gastric, 7 small intestinal; p=0.0019), five schwannomas (three gastric, two small intestinal; p=0.154) and 35 non-GILM (p=0.0001). The densities of CA ranged from one per 4–200u2005mm2. CA stained intensely with periodic acid Schiff after diastase predigestion (PASD), Alcian blue and ubiquitin, and faintly in peripheral zones for desmin and smooth muscle actin. Ultrastructurally, CA consisted of an electron-dense outer layer and a fibrillar core with scattered particle matter. HG were present in all leiomyomas, but showed variable staining for PASD, negative staining for Alcian blue and ubiquitin, and positive staining for smooth muscle markers. Conclusions CA are a distinctive histological feature of approximately one third of GILM with different composition to HG. These differences may represent divergent degenerative processes or different stages of a single degenerative process over time.

Intraductal Polypoid Lipid-Rich Neuroendocrine Tumor of the Pancreas with Entrapped Ductules: Case Report and Review of the Literature

Pancreatic neuroendocrine tumors of the main pancreatic duct are rare and usually small due to symptoms of pancreatic duct obstruction. We present a case of a large (3xa0cm), well-differentiated (G1) lipid-rich polypoid neuroendocrine tumor of the pancreas completely occluding the main pancreatic duct with non-neoplastic-entrapped ductules and CK19 positivity. Clinical, radiological, gross, microscopic, immunohistochemical, and ultrastructural findings are discussed. The literature pertaining to the unique features of this case is reviewed including clinical and pathologic pitfalls and the possible etiologic and prognostic significance of these findings.

Hepatic Mass in a 73-Year-Old Man

Question: A 73-yearold man with history of hypertension and dyslipidemia was incidentally found to have a large liver mass on magnetic resonance imaging. He did not have a personal or family history of chronic liver disease, previously diagnosed malignancy, alcohol use, blood transfusion, or smoking. Physical examination revealed abdominal distention. A palpable mass and jaundice were absent. Comprehensive metabolic panel, complete blood count, alpha-fetoprotein, liver transaminases, and carcinoembryonic antigen were within reference range. Carbohydrate antigen 19-9 was elevated 45.8 U/mL). Serologic studies for hepatitis B surface antigen and hepatitis C core antigen were negative. Antibody to hepatitis B surface antigen as positive. Computed tomography (CT) was performed, revealing a large right hepatic lobe mass, 20 cm in greatest dimension (Figure A). he mass had predominantly fatty attenuation with interspersed wispy soft tissue attenuation, multiple scattered small round enhancing odules, and prominent dilated irregular enhancing vessels. A right lobectomy was performed. Pathologic examination of the 3503.6-g resection specimen revealed a 22 cm, well-circumcribed yet unencapsulated yellow-tan variegated soft mass with hemorrhagic foci (Figure B). The uninvolved hepatic parenchyma as grossly unremarkable. Histologically, the mass consisted of a mixture of smooth muscle cells (arrows), abnormal thick-walled lood vessels, mature adipose tissue, and foci of hematopoietic elements (Figure C). The smooth muscle cells were positive for the elanocytic lineage marker homatropine methylbromide 45 (HMB-45) (Figure D). What is the diagnosis? Look on page 679 for the answer and see the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.