Fumihiro Ogawa

IgG4+ to IgG+ plasma cells ratio of ampulla can help differentiate autoimmune pancreatitis from other "mass forming" pancreatic lesions.

Autoimmune pancreatitis (AIP) shows a unique spectrum of histologic features and commonly presents with an abundant IgG4-positive (IgG4+) plasma cell infiltration. However, differentiating AIP from other mass lesions, particularly pancreatic cancer [invasive ductal carcinoma (IDC)] can be clinically challenging. In this study, we evaluated the validity of IgG4 and IgG immunohistochemistry of ampullary and periampullary tissue for the diagnosis of AIP. Our study group consisted of 14 resected AIP cases with appropriate ampullary sections. Superficial ampullary tissue and “shouldering” duodenal mucosa were evaluated for several histologic variables. Immunohistochemistry for IgG4 and IgG was performed. The number of IgG4 and IgG-positive plasma cells was counted and an IgG4+ to IgG+ plasma cells ratio (IgG4/IgG ratio) was evaluated. A control cohort was composed of IDC (n=30) and chronic pancreatitis (CP) (n=29). Although an overlap was present between the groups, the overall inflammation and number of plasma cells in and around the ampulla was significantly increased in AIP compared with CP and IDC. Furthermore, although there was some overlap in the crude number of IgG4+ plasma cells of the ampullary and duodenal tissue between AIP, IDC, and CP, an IgG4/IgG ratio, especially of the ampulla, seems diagnostically useful in differentiating AIP from other “mass forming” lesions. When a cut-off of 0.10 was applied, the diagnostic sensitivity and specificity of the ampullary IgG4/IgG ratio was 86% and 95%, respectively. In conclusion, evaluation of ampullary histology and IgG4/IgG ratio might be proven beneficial in discriminating AIP from other mass forming pancreatic lesions.

Gastroduodenitis Associated With Yttrium 90-Microsphere Selective Internal Radiation An Iatrogenic Complication in Need of Recognition

CONTEXT Selective internal radiation (SIR) therapy (SIRT) with yttrium 90 microspheres is increasingly used as an alternative therapeutic modality for patients with inoperable liver tumors. During administration of microspheres via the hepatic artery branches, some may on occasion be misdirected and be caught in the capillary bed of the duodenal and/or stomach. OBJECTIVE To better characterize the histopathologic features of these complications. DESIGN We report herein our experience with 3 patients who received SIR and developed gastroduodenal complications. RESULTS SIR-microsphere-induced gastroduodenitis was diagnosed from 10 days to 5 months after treatment. In all 3 cases, purple particles measuring about 40 microm in diameter were observed. An array of changes ranging from mucosal ulceration to epithelial changes were seen. Fibrinopurulent exudate was admixed with granulation tissue and reactive stromal cells. Epithelial changes included apoptosis and mucin depletion. Glandular cystic dilatation and epithelial flattening were also common as well as foveolar hyperplasia, suggestive of reparative changes in one case. Capillary ectasia and prominent plump endothelial cells were also present. CONCLUSION The spectrum of the alterations is consistent with radiotherapy-induced changes. Given the recent approval by the US Food and Drug Administration for the use of SIRT, it is anticipated that more patients will be treated with this modality. Pathologists should become aware of the adverse effects associated with its use.

Chorioangioma: antenatal diagnosis with fast MR imaging

We report a case of chorioangioma of the placenta, in which fast magnetic resonance imaging (MRI) was useful adjunct to ultrasonography for the antenatal diagnosis. MRI allowed clear demonstration of 6.8 x 6.0 cm solid placental mass along with hydramnios and anatomically normal fetus. On T(1)-weighted breath-hold spoiled gradient-echo (fast low-angle shot [FLASH]) images, chorioangioma was mostly isointense to the placenta, but had an area of high signal intensity near the base and at the periphery, suggestive of hemorrhage. On T(2)-weighted half-Fourier single-shot fast spin echo (HASTE) images, the mass showed heterogeneous high signal intensity, but had an area of low signal intensity near the surface.

Immunohistochemical evaluation of KIT expression in sarcomas of the gynecologic region

Summary: KIT is expressed in most gastrointestinal stromal tumors, and they usually show c-kit aberrations (most frequently deletions or deletions coexisting with a single or multiple point mutations). Recently, several studies regarding KIT expression in gynecologic tumors have been reported; however, their outcomes were not consistent. In this study, we immunohistochemically examined KIT expression in sarcomas of the female genital tract and studied the existence of c-kit aberrations to elucidate the characteristics of KIT-positive tumors in the gynecologic region. Formalin-fixed, paraffin-embedded tissues from 25 surgically resected and 1 biopsy specimen from 26 patients were used. Histological diagnoses included 14 uterine leiomyosarcomas, 6 carcinosarcomas, 5 endometrial stromal sarcomas, and 1 vaginal epithelioid sarcoma. Immunohistochemical studies were performed using anti-KIT polyclonal antibody. Only four of the above tumors (15%) were positive for KIT, all of which were carcinosarcomas. Specific KIT immunoreactivity was observed in the only carcinomatous components in one case, in the only sarcomatous component in two cases, and in the both components in one case. However, none of the cases showed c-kit aberrations in exons 9, 11, 13, and 17. Judicious decision is mandatory before applying Imatinib therapy to KIT-positive gynecologic tumors.

Post-gastric endoscopic mucosal resection surveillance biopsies: evaluation of mucosal changes and recognition of potential mimics of residual adenocarcinoma.

Endoscopic mucosal resection (EMR) offers curative treatment for patients with node-negative early gastric carcinoma of less than 2 cm without ulceration or ulceration scar. Follow-up biopsies are frequently performed to ensure the absence of residual neoplasia. We performed a retrospective analysis of post-EMR biopsies from 33 patients who underwent gastric EMR. Histologic changes included inflammation (100%), stromal edema (97.0%), foveolar hyperplasia (78.8%), ectatic vessels (66.7%), epithelial atypia (60.6%), increased glandular mitoses (57.6%), epithelial anisonucleosis (54.5%), fibrinopurulent materials (51.5%), ischemia (48.5%), stromal hemorrhage (33.3%), mucin depletion (12.1%), clear cell degeneration (15.2%), and signet-ring cell-like change (6.1%). Especially, clear cell degeneration and signet-ring cell-like change were conspicuous in the area of ischemia. Residual adenocarcinomas were noted in 4 of 33 cases, and consistently showed high nuclear-to-cytoplasmic ratio with high glandular density. Glandular clear cell degeneration and/or signet-ring cell-like change were worrisome and sometimes difficult to be distinguished from residual neoplastic glands. However, these degenerative glands were usually embedded in a nondesmoplastic stroma and showed anisonucleosis of glandular epithelia. Mimics of residual adenocarcinoma, namely clear cell degeneration and signet-ring cell-like change should be judiciously assessed to avoid unnecessary surgery.

Squamous cell carcinoma of the skin: dual differentiations to rare basosquamous and spindle cell variants

Abstract:  Basosquamous carcinoma (BSC) is defined as a tumor containing the areas of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a transition zone linking the two. Spindle cell squamous carcinoma (SCSC) may have a variable component of conventional SCC and spindle cells. We present a case of an 89‐year‐old woman with an eruption on the scalp for several decades. Grossly, the lesion measured 8.5 × 6.0 × 1.8 cm and consisted of a gray‐white and focally black tumor. Microscopically, a non‐ulcerated upper part of the tumor consisted of large polygonal squamoid cells with occasional keratinization (SCC), trabecular growth of basaloid cells with peripheral palisading (BCC), and an area in which both the components were intermingled. The rest of the tumor was a myxoid area with elongated fusiform spindle cells, which appeared to arise from conventional SCC. Immunohistochemically, the tumor cells in the SCSC (both conventional and spindle cell) area co‐expressed CAM5.2, and vimentin. Ber‐EP4 was positive in the BCC area with the transition zone of SCC and BCC showing diminished staining. Epithelial membrane antigen was focally positive in the conventional SCC area. To our knowledge, this is the first case report of SCC of the skin that has dual differentiations to BSC and SCSC.

Clinicopathologic features of epidermal cysts of the sole: comparison with traditional epidermal cysts and trichilemmal cysts*

Background:  It has been described that the etiology of epidermal cysts on acral skin is different from that on non‐acral skin; however, no papers have been published regarding the detailed histological differences between acral and non‐acral epidermal cysts. In this study, we compared the clinicopathologic findings of epidermal cysts of the sole with those of traditional epidermal cysts and trichilemmal cysts.

Gastric hyperplastic polyps: a heterogeneous clinicopathologic group including a distinct subset best categorized as mucosal prolapse polyp.

BackgroundGastric hyperplastic polyps are the second most common subtype of gastric polyps. There has been an ongoing debate about their precise diagnostic criteria and etiological associations. Materials and MethodsA total of 208 gastric polyps that were originally diagnosed as hyperplastic polyps in our department during an 8-year period were reviewed using recently emphasized diagnostic criteria, and their clinicopathologic associations were explored. ResultsOnly 41 cases were confirmed as hyperplastic polyps, whereas 103 cases (49%) were reclassified as polypoid foveolar hyperplasia, and 64 cases (31%) were diagnosed as gastric mucosal prolapse polyps. Gastric mucosal prolapse polyps were distinguished by basal glandular elements, hypertrophic muscle fibers ascending perpendicularly from the muscularis mucosae, and by thick-walled blood vessels. This hitherto undescribed polyp is more commonly sessile than hyperplastic polyps (P=0.0452) and is found more often in the antropyloric region (P: 0.0053). Only 20.6% of hyperplastic polyps were associated with Helicobacter pylori infection. ConclusionsOur findings highlight that gastric polypoid lesions that have morphologic similarities may be related to various mechanisms, including inflammatory and prolapse processes. The predominantly antral location of gastric mucosal prolapse polyps, a zone of pronounced peristalsis, suggests that mucosal prolapse plays a role in the development of these common polyps. Evaluation of the prevalence and clinical associations of these distinctive polyps awaits further studies.

Lymphoglandular bodies in malignant tumors: with special reference to histologic specimens.

Lymphoglandular bodies (LGBs) have been described as cytoplasmic fragments of lymphocytes and a specific feature of organized lymphoid tissue. The recognition of LGBs is useful in distinguishing malignant lymphomas from carcinomas and sarcomas in cytology specimens, especially in Giemsa-stained tissues. So far, there has been no description of LGBs in hematoxylin and eosin (HE)-stained histologic specimens in the literature. Therefore, we evaluated LGBs in HE sections, especially regarding malignant tumors. We reviewed 110 biopsy and surgical materials including malignant lymphoma, carcinoma, and other malignant tumors and evaluated the frequency, number, size, and significance of LGBs. We also performed the terminal deoxyribosyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method on LGBs. Lymphoglandular bodies were found in about 40% of cases with malignant lymphoma, whereas only 3 (3.8%) nonlymphoma cases showed LGBs. These were undifferentiated carcinoma, seminoma, and multiple myeloma. The size of LGBs was usually less than half the size of a red blood cell. No apoptotic cells were detected in any of the cases by TUNEL method regarding LGBs. Our study suggests that LGBs can be found in HE sections. As observed in cytologic specimens in the literature, the presence of LGBs around cytologically malignant cells favors a diagnosis of malignant lymphoma rather than nonlymphoma malignancies, even in HE histologic sections.

Primitive Neuroectodermal Tumors of the Female Genital Tract: A Morphologic, Immunohistochemical, and Molecular Study of 19 Cases

Primary primitive neuroectodermal tumor (PNET) of the female genital tract is rare, and its proper classification remains unclear. The clinical, histologic, and immunophenotypic features as well as EWSR1 rearrangement status of 19 gynecologic PNETs, including 10 ovarian, 8 uterine, and 1 vulvar tumors, are herein reported. Patient age ranged from 12 to 68 years, with a median age of 20 and 51 years among those with ovarian and uterine PNETs, respectively. Morphologic features of central nervous system (CNS) tumors were seen in 15 PNETs, including 9 medulloblastomas, 3 ependymomas, 2 medulloepitheliomas, and 1 glioblastoma, consistent with central PNET. The remaining 4 PNETs were composed entirely of undifferentiated small round blue cells and were classified as Ewing sarcoma/peripheral PNET. Eight PNETs were associated with another tumor type, including 5 ovarian mature cystic teratomas, 2 endometrial low-grade endometrioid carcinomas, and a uterine carcinosarcoma. By immunohistochemistry, 17 PNETs expressed at least 1 marker of neuronal differentiation, including synaptophysin, NSE, CD56, S100, and chromogranin in 10, 8, 14, 8, and 1 tumors, respectively. GFAP was positive in 4 PNETs, all of which were of central type. Membranous CD99 and nuclear Fli-1 staining was seen in 10 and 16 tumors, respectively, and concurrent expression of both markers was seen in both central and Ewing sarcoma/peripheral PNETs. All tumors expressed vimentin, whereas keratin cocktail (CAM5.2, AE1/AE3) staining was only focally present in 4 PNETs. Fluorescence in situ hybridization was successful in all cases and confirmed EWSR1 rearrangement in 2 of 4 tumors demonstrating morphologic features of Ewing sarcoma/peripheral PNET and concurrent CD99 and Fli-1 expression. In conclusion, central and Ewing sarcoma/peripheral PNETs may be encountered in the female genital tract with central PNETs being more common. Central PNETs show a spectrum of morphologic features that overlaps with CNS tumors but lack EWSR1 rearrangements. GFAP expression supports a morphologic impression of central PNET and is absent in Ewing sarcoma/peripheral PNET. Ewing sarcoma/peripheral PNETs lack morphologic features of CNS tumors.