International Journal of Surgical Pathology

A number of transcription factors have been identified as important in guiding normal Schwann cell development. This study used immunohistochemistry on tissue arrays to assess the expression of some of these transcription factors (Sox5, Sox9, Sox10, AP-2α, Pax7, and FoxD3) on 76 schwannomas, 105 neurofibromas, and 34 malignant peripheral nerve sheath tumors (MPNSTs). Sox9 and Sox10 were found to be widely expressed in all tumor types. FoxD3 reactivity was stronger and more frequently found in schwannomas and MPNSTs than neurofibromas. AP-2α was positive in 31% to 49% of all tumors, but strong reactivity was limited to MPNSTs and schwannomas. Pax7 and Sox5 expression was restricted to subsets of MPNSTs. Statistical analysis showed significant differences between the 3 tumor types in the expression of these markers. No differences were found in the analyzed tumor subgroups, including schwannomas of different sites, schwannomas with or without NF2 association, neurofibromas of different types, or sporadic versus NF1-associated MPNSTs. These results suggest that the transcription factors that guide normal Schwann cell development also play a role in the biology of neoplastic cells with Schwannian differentiation. FoxD3, AP-2α, Pax7, and Sox5 are upregulated in MPNSTs compared with neurofibromas and may be markers of malignant transformation. Screening the expression of FoxD3, Sox9, and Sox10 on 23 cases of other spindle-cell proliferations that may be considered in the differential diagnosis of MPNST, including synovial sarcoma and spindle cell melanoma, suggests that these 3 are helpful markers of Schwannian differentiation in the context of diagnosing MPNSTs.

Objectives. Renal cell carcinomas (RCCs) in children and adolescents are much rarer than in adults. In this age group, Xp11.2 translocation RCCs were the most common subtype of pediatric RCCs. Information regarding the clinical behavior of pediatric RCCs remains controversial because of their relatively rare incidence. The authors aimed to perform a systematic review and meta-analysis to better define the biological features of pediatric RCCs. Methods. Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Jadad Quality Scale. Data were collected comparing overall survival (OS), disease-free survival (DFS), and stage in patients with TFE3 + pediatric RCCs and TFE3 − RCCs. Results. A total of 4 studies were included for meta-analysis, and pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated. The meta-analysis outcomes showed that TFE3 + pediatric RCCs were significantly associated with poorer outcomes (OS and DFS) and a higher stage (III/IV) than TFE3 − RCCs (pooled ORs for each group: 4.59 [95% CI = 1.46-14.42] for OS; 5.79 [95% CI = 1.85-18.16] for DFS; and 5.89 [95% CI = 2.23-15.52] for stage). This result was also confirmed by OS and DFS curves (P = .005 and P = .001). Conclusions. Xp11.2 translocation carcinomas appear to have a poorer prognosis than non-Xp11.2 translocation carcinomas in children and young adults.

Abnormal substances in the nuclei that can be observed by light microscopy are often broadly referred to as nuclear inclusions. Although their recognition in the appropriate clinicopathological settings can aid in the diagnosis of some disease entities and tumor types, they can also be a source of error. There are 2 morphologically distinct types of inclusions with different mechanisms of formation and diagnostic significance, including bona fide nuclear inclusions and nuclear pseudoinclusions. Bona fide nuclear inclusions result from accumulation in the nuclei of viral particles, cytoplasmic materials (such as surfactant, immunoglobulin, and glycogen), biotin, nuclear lamins, or polyglutamine. Some of them are diagnostically helpful, such as surfactant inclusion, which can support the pulmonary origin of an adenocarcinoma, whereas others may be misleading, such as biotin inclusion, which can be mistaken for herpes infection. Nuclear pseudoinclusions, which represent invaginations of cytoplasm into the nucleus, are delimited by the nuclear membrane. Although not totally specific, they are particularly common in papillary thyroid carcinoma, meningioma, and usual ductal hyperplasia of the breast and hence may aid in the diagnosis of these entities. Nuclear pseudo-pseudoinclusions, which are artefactual bubbles in the nuclei that mimic nuclear pseudoinclusions or clear nuclei, can lead to misdiagnosis of follicular adenoma or hyperplastic nodule as papillary thyroid carcinoma.

Background. The diagnosis of acute cellular rejection (ACR) in small-bowel allograft biopsies depends in part on quantification of crypt apoptotic bodies (ABs). The definition of ABs varies between authors. Recently, immunoperoxidase stains specific for apoptotic material have been used in paraffin-embedded tissue. The aim was to characterize AB morphology and quantify ABs using immunoperoxidase and hematoxylin and eosin (H&E) staining. Methods. Allograft biopsies with diagnoses of negative for ACR, indeterminate for ACR, and mild ACR were selected. Sections were stained for cleaved caspase 3 (CC3). The number of ABs per 10 crypt epithelial cells was compared by H&E and CC3 staining. Results. A total of 39 cases (15 negative, 12 indeterminate, 12 mild ACR) were obtained. CC3 staining revealed that ABs varied from well-developed “classical” exploding crypt cells to intraepithelial clusters of basophilic material. In 61%, the number detected by CC3 was higher than on H&E stains (mean 4.30 and 3.56; P < .002), with good overall correlation. With the latter definition, AB numbers by H&E were significantly higher in most cases (72%), with the diagnosis of mild ACR being downgraded in 50% if only classical ABs were counted. Conclusions. ABs have a range of morphology in biopsies of intestinal allografts, and H&E identifies the majority. The results suggest that AB counts should include basophilic clusters.

Goblet cell carcinoid (GCC) of the appendix is characterized by a dual differentiation of both endocrine and gland. This study, therefore, explores its clinicopathological and immunohistochemical features. The authors reviewed clinicopathological and immunohistochemical features of 26 GCC cases in Southwest China between 1991 and 2009. The incidence is 0.0453%, with a gender ratio of 2.71:1 (19 males and 7 females). Three cases were combined with schistosomiasis, suggesting schistosomiasis may be associated with GCC. Eighteen cases available for immunohistochemistry showed a few scattered positive cells for CD56, NSE, CgA, and Syn; diffuse positive for CEA; and preserved positive for E-cadherin and β-catenin. Follow-up data showed that 1 patient died from peritoneal metastasis and that the other 17 cases survived free of the tumor. The authors characterize GCC as a special low-grade malignant carcinoma with a primary epithelial differentiation and little neuroendocrine differentiation. A combination of both histological features and immunoreactivity is needed to diagnose GCC.

Cardiac myxoma is the most common primary tumor of the heart. The existence of apoptosis in cardiac myxoma has been demonstrated. The purpose of this investigation was to elucidate the pathway of apoptosis and the cell cycle in cardiac myxomas. This study had 2 parts: investigation of a cultured cardiac myxoma cell line and the analysis of data from 20 patients with cardiac myxoma that was surgically excised. Apoptosis signal transduction was determined by assessing DNA fragmentation, Fas ligand (FasL), Fas, tumor necrosis factor-α (TNF-α), caspase-3, and terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay through immunohistochemical stain, quantitative reverse transcriptase— polymerase chain reaction (RT-PCR), and Western blot analysis. The patient population consisted of 12 (60%) women and 8 (40%) men with a mean age of 46 years (range = 32-64 years). All cases of myxoma were sporadic myxomas rather than familial. Clinical presentations included asymptomatic (26%), dyspnea (44%), stroke (9%), chest pain (9%), and fever (11%). All myxomas were located in the left atrium. Pathological scores for inflammation, cellularity, calcification, and thrombosis were not related to myxoma location or clinical events. In cardiac myxoma, apoptosis documented by TUNEL (70.9% ± 17.6%) and the caspase-3 (66.5% ± 32.5%) final common pathway is characterized by the extrinsic Fas/ FasL dependent pathway (positive stained 70.9% ± 19.2%; 26.0% ± 17.2%, respectively), but not the intrinsic pathway. The RT-PCR and Western Blot analysis (Fas/FasL, TNF-α, caspase-3, and apoptosis) of the cardiac myxoma and cultured cardiac myxoma cells confirmed the immunochemical results. The extrinsic Fas/FasL-dependent apoptosis pathways in cardiac myxomas were proved by both RNA and protein levels.

Objective: To identify the magnitude and possible predictors of contralateral lobe involvement and contralateral extraprostatic extension (EPE) in prostatic biopsy—defined localized unilateral cancers. Patients and Methods: Between January 2005 and August 2009, 1861 patients underwent robotic-assisted radical prostatectomy at the authors’ institution. A total of 1114 had unilateral disease on preoperative biopsy. Final histopathology reports of these patients were reviewed. Results: Of the 1114 patients with unilateral disease on biopsy, 867 (77.9%) had contralateral or bilateral disease on final histopathology. EPE was found in 132 patients (11.9%). Twenty patients (1.8%) had contralateral EPE involvement. High-grade prostatic intraepithelial neoplasm (HGPIN) on biopsy was the significant predictor of contralateral lobe involvement on both univariate (P = .02; odds ratio [OR] = 1.791) and multivariate analysis (P = .004; OR = 2.677). Clinical stage T2 was the significant predictor of contralateral EPE on both univariate (P = .012; OR = 5.250) and multivariate analysis (P = .007; OR = 8.656). Conclusion: HGPIN on biopsy significantly predicts for contralateral lobe involvement and should be considered an exclusion criterion for focal therapy in prostate cancer patients. Patients with palpable tumor on digital rectal examination should be advised in favor of radical treatment as these patients may harbor more aggressive tumors involving the contralateral side despite the biopsy findings.

Elastofibroma is a tumorlike lesion occurring usually in the subscapular region of elderly females. In this study, 18 cases of elastofibromatous tissue retrieved from the spinal canal were analyzed to elucidate its frequency and possible clinical associations. The patients included 8 men and 10 women with a mean age of 63.4 years (range, 40-84 years). The elastic nature of the material was confirmed by Weigert’s elastic stain and immunohistochemically. Elastofibroma was diagnosed in 6 patients, and elastofibroma-like tissue was found in 11 samples. The finding of elastofibromatous tissue was associated with clinical diagnosis of juxtaarticular cysts (3 cases), thickening of ligamentum flavum (4 cases), extradural expansion (2 cases), metastatic involvement of the dorsal spine (3 cases), and a vertebral fracture (1 case). Two cases were located above the transpedicular fixation. Elastofibromatous tissue may be found in approximately 2.6% of all spinal biopsies and it may take part in compression of spinal cord and nerve roots.

This study reports the case of a 39-year-old woman with tuberous sclerosis complex (TSC) combined lymphangioleiomyomatosis (LAM), multifocal micronodular pneumocyte hyperplasia (MMPH), and clear-cell micronodules. She had repetitious bilateral pneumothoraces, and chest radiography revealed diffuse thin-walled cysts and multiple nodules. Bilateral renal angiomyolipomas (AMLs) and cerebral periventricular spots were also present. Lung biopsy revealed dilated airspace with HMB-45-positive spindle cell infiltration and aggregation indicative of LAM. Randomly distributed nodules of proliferative type II pneumocytes were consistent with MMPH. Clear-cell micronodules comprised nodular aggregation of HMB-45-positive polygonal cells with clear cytoplasm. Abnormal migration and proliferation of HMB-45 immunoreactive perivascular epithelioid cells (PEComas) is posited to indicate LAM and AML histogenesis. Clear-cell micronodules are also believed to be one of the families of PEComas and are reported in association with TSC. These behaviors of perivascular epithelioid cells may play a role in TSC.

The authors describe a rare case of thymolipoma in a 26-year-old, otherwise healthy woman presenting with general fatigue. Radiological examinations disclosed a large anterior mediastinal mass. Macroscopically, the resected tumor was approximately 5 × 10 cm², with nodular configuration, and microscopically, 3 components were identified: a normal thymic rim, hyperplastic thymic tissue, and a typical thymolipomatous component at the periphery of the hyperplastic area. The predominant component of the tumor was hyperplastic thymic tissue. The tumor was diagnosed as thymolipoma at the initial stage of development. This case suggests the histogenesis of thymolipoma—fatty regression or infiltration of fatty tissue into a previously hyperplastic thymus.

A 44-year-old male with a mediastinal mass measuring 3.5 × 3.5 × 3 cm was diagnosed with papillary adenocarcinoma of the thymus. Other origins of papillary adenocarcinoma were excluded by clinical, imaging, and immunocytochemical methods before assuming this diagnosis. Residual thymus was seen under the microscope. Focal CD5 immunoreactivity was present. There was no associated thymoma. The patient underwent surgery, radiotherapy, and chemotherapy. He disclosed systemic recurrence at 18 months (subcutaneous nodule). He is alive after 24 months of follow-up with active disease. There had been only 7 cases of this rare entity published before.

A 25-year-old patient presented with epigastric pain, which on gastric biopsy revealed the characteristic appearance of collagenous gastritis. There was a thick prominent subepithelial band that was confirmed to be collagen with a Masson’s trichrome stain. There was associated Helicobacter pylori gastritis but no evidence of a lymphocytic gastritis. The patient did not have watery diarrhea. Collagenous gastritis can occur in young patients, be restricted to the stomach, and can be associated with celiac disease.

We report a case of hepatic angiomyolipoma associated to a small bowel schwannoma in a 40-years old woman. Both lesions were asyntomatic. Histologically, hepatic angiomyolipoma showed oncocytic features and scanty adipose tissue, the tumor cells expressed desmin, smooth muscle actin, S-100 protein and HMB45. The tumor cells of intramural small intestinal mass were positive for S-100 protein and GFAP and negative for CD117, CD34 and desmin. To the best of our knowledge, no case of hepatic angiomyolipoma has been previously reported in association with intestinal schwannoma.

Rosai—Dorfman disease (RDD; sinus histiocytosis with massive lymphoadenopathy) is a rare, usually nodal self-limited disease. Sometimes nodal disease is coupled with extranodal localizations, in which case the disease can follow a protracted clinical course characterized by remissions and relapses and, exceptionally, a fatal outcome. Exclusive extranodal localizations are rare and their prognosis variable. This study reports a case of RDD apparently limited to the liver coexisting with a diffuse (stage IV) relapsing follicular lymphoma. The patient is alive and well 24 months after the diagnosis of the lymphoma. It is conceivable that the lymphoma has induced RDD via an immunological disorder, possibly involving interleukin expression. The favorable outcome supports the belief that the prognosis of RDD is largely dependent on the number of extranodal sites involved, rather than on the specific sites themselves.

Extramedullary hematopoiesis (EMH) is a phenomenon in which benign immature hematopoietic cells are found in sites other than the bone marrow. Although usually associated with an underlying hematologic abnormality such as myelofibrosis, it can be found in some physiologic states or occasionally within solid tumors. In most instances, foci of EMH contain elements of all cell lineages. Presented here is the second reported case of EMH occurring in a low-grade clear cell renal cell carcinoma in a patient without evidence of hematologic disease. As previously, it manifested as pure erythropoiesis as confirmed by morphology and immunohistochemistry. It is possible that this finding is related to erythropoietin secretion by the tumor and not hematologic malignancy.

Simple melanosis of the bladder is an uncommon condition with fewer than 15 reported cases characterized by multifocal, diffuse melanin pigmentation of the urothelial mucosa. It is frequently associated with urinary incontinence or urgency. Histologically, melanin granules are present within urothelial cells or lamina propria macrophages with or without bland-appearing mucosal melanocytes. Although considered a benign entity, the rarity of the lesion warrants regular follow-up cystoscopic evaluation with biopsies to screen for the development of malignancy, especially malignant melanoma. This study presents a “typical” case with light, cytochemical, immunohistochemical, and ultrastructural characterization.

Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.

Endobronchial metastasis from a prostate cancer is uncommon. Diagnosis of prostate carcinoma after primary presentation with an endobronchial mass is very rare. The authors describe the case of an 84-year-old man with endobronchial metastases from prostatic carcinoma presenting primarily with pulmonary symptoms. The diagnosis of prostate cancer and endobronchial metastases was made by a bronchoscopic bronchial biopsy and confirmed by immunohistological staining with prostate-specific antigen. The importance of this manifestation along with clinical and therapeutic implications is discussed here.

A 55-year-old woman underwent a total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy, and lymphadenectomy for endometrial cancer. Histologically, the cancer was endometrioid adenocarcinoma grade 1, which invaded the myometrium. There was no macroscopically detectable mass in the ovaries. However, histological examination revealed a small tumor, 1 mm in size, in the medulla of the right ovary. The ovarian tumor was composed of uniform epithelioid cells that grew in nests. Vessels of various sizes were observed within the tumor, and they were surrounded by tumor cells. Immunohistochemically, the ovarian tumor was positive for smooth muscle actin and vimentin but negative for desmin and CD34. Based on these findings, the authors made the diagnosis of ovarian glomus tumor. Although an ovarian glomus tumor is extremely rare, the authors believe that it should be included in the differential diagnosis of ovarian mesenchymal tumors and sex cord tumors.

We report a mature solid teratoma of the fallopian tube in an elderly woman. This mass was noted on CT scan and considered metastatic in nature since following a bioptical diagnosis of endometrial adenocarcinoma. Hysterectomy and bilateral salpingectomy and ovariectomy were performed and a second minor mature solid teratoma was discovered inside the right ovary. Neoplasms of the fallopian tube are very uncommon and this is the first Italian case to be added to about other 60 of the literature. Moreover it joins minimum teratomatous diameter with maximum recorded age.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferation of the hormonally responsive, specialized mammary stroma characterized by slit-like pseudovascular spaces lined by bland spindle cells. It is usually an incidental microscopic finding but in some cases it may present as a slowly growing mass. A malignant counterpart for this lesion has not been reported. We describe a case of PASH with foci of malignant histologic features presenting as a slowly growing mass in a 30-year-old woman. The previously reported variants of PASH and the other mammary stromal lesions related to PASH are also discussed. This is perhaps the first case of PASH with foci of malignant histologic features reported in the literature and represents a rare sarcoma derived from specialized hormonally responsive mammary stroma.

The development of squamous metaplasia or carcinoma is a rare occurrence in the setting of a ruptured or leaking silicone breast implant capsule. However, the oncogenic process in such a context is yet another intriguing example of how chronic inflammation plays an integral role in the tumorigenic process. Recent papers have shed light on how inflammation involving M2-tpe macrophages, lymphocytes, and other inflammatory cells at first provide the cytokines necessary to fend off an inciting foreign-body attack such as silicone from a ruptured or leaking implant. Although such a response is beneficial in keeping infection or foreign material in check, there are instances when the response may be exaggerated. It is thought that the extent and length of the response, the balance between pro-inflammatory/ anti-apoptotic and anti-inflammatory/pro-apoptotic, as well as genetic factors play important roles in determining the final result of an inflammatory insult.

Breast spindle cell tumors (BSCTs), although uncommon, constitute a heterogeneous group of benign and malignant lesions, often necessitating different therapeutic approaches. This study describes the case of a 62-year-old man who displayed a gradually growing retroareolar tumor of the left breast. The mass was well circumscribed, unilateral, and grossly nodular. The patient eventually underwent wide local excision of the mass. The lesion was made up of spindle cells arranged in fascicular clusters, separated by bands of collagen. No mitotic figures were observed. Immunohistochemically, the mass expressed strong and diffuse cytoplasmic staining for vimentin, CD34, CD10, and bcl-2, whereas it was negative for cytokeratins, smooth muscle actin, desmin, S-100 protein, p53, Ki-67, estrogen and progesterone receptors. Diverse histological results and immunohistochemical features established the diagnosis of benign BSCT, not otherwise specified. The patient remains disease-free 12 months after lumpectomy. This case report adds to the spectrum of the benign BSCTs and delineates the nature of different types of these lesions, in order to carefully select optimal therapeutic regimes.

Capillary hemangioblastoma (CHB) is a benign, highly vascularized tumor that generally occurs in the central nervous system either in the setting of von Hippel-Lindau (VHL) disease or, more often, as a solitary sporadic lesion that is increasingly recognized in extraneural sites. We present the case of a 72-year-old woman with low back pain and a well-demarcated lytic lesion of the sacrum, which at histological and ultrastructural examination was indistinguishable from central nervous system CHB. The patient had no signs of VHL disease and died of another cause with no evidence of disease 57 months after curettage of the lesion. To our knowledge, this is the second case of CHB reported to occur in bone.

Malakoplakia is an uncommon chronic inflammatory disorder, which is characterized by the presence of histiocytes containing concentric concretions known as Michaelis-Gutmann bodies in a background of mixed inflammation. The urinary tract is the most commonly involved site. However, malakoplakia can be found in a wide range of other organs throughout the body. Its occurrence has been attributed to a defect in the bactericidal capacity of phagocytic cells, and it is usually seen in patients with some degree of immunologic compromise. A case of malakoplakia of the spleen in a patient with Crohn’s disease is reported in this article.