A Case of Small Cell Carcinoma of the Maxillary Sinus with Distant Metastasis / 대한내과학회지

Primary small cell carcinoma of the paranasal sinuses is extremely rare. It is aggressively locally invasive, with high recurrence and metastatic rates. A combination of systemic chemotherapy and locoregional treatment, such as radiotherapy, is currently recommended based on the treatment of small cell carcinoma of lung. We report a case of small cell carcinoma originating from the maxillary sinus with distant metastasis at the time of diagnosis. The patient had a good initial therapeutic response to etoposide-cisplatin chemotherapy, but the cancer progressed after the sixth cycle of chemotherapy and the prognosis was poor.

Primary mesenteric carcinoid tumor / 대한외과학회지

Primary mesenteric carcinoid tumor is very rare, although secondary mesenteric involvement is common, reported as 40% to 80%. And distant metastasis rate reported as 80% to 90%, when the size is larger than 2 cm. We present a case of very rare primary mesenteric carcinoid tumor showing benign character though large size. The patient visited St. Vincent's Hospital, The Catholic University of Korea with increasing palpable abdominal mass. At laparotomy, a well encapsulated mass arising from the mesentery near the ligament of Treitz was found without any adjacent organ invasion or distant metastasis. The mass was measured as 8.2 x 7.3 cm and histopathologically benign character. At 11 months of follow up, the patient was recurrence free.

Microtubule-Associated Protein Tau, alpha-Tubulin and betaIII-Tubulin Expression in Breast Cancer

BACKGROUND: The microtubule-associated protein Tau binds to both inner and outer surfaces of microtubules, leading to tubulin assembly and microtubule stabilization. The aim of this study was to evaluate the significance of Tau, alpha-tubulin, and betaIII-tubulin expression in breast carcinoma and to assess their relationships with disease progression in the context of taxane treatment. METHODS: Immunohistochemical expressions of Tau, alpha-tubulin, and betaIII-tubulin were assessed in 183 breast cancer cases. Expression was correlated with clinicopathologic parameters, disease progression and overall survival. RESULTS: Tau expression was correlated with lymph node metastasis and estrogen receptor (ER) positivity (p=.003 and p<.001, respectively). Loss of alpha-tubulin was significantly correlated with distant metastasis (p=.034). Loss of betaIII-tubulin was correlated with lymph node metastasis and ER positivity (p=.004 and p<.001, respectively). In taxane-treated cases, Tau expression and loss of alpha-tubulin and betaIII-tubulin expression were related to disease progression (p=.001, p=.028, and p=.030, respectively). Tau expression was associated with a worse survival rate in taxane-treated patients (p=.049). CONCLUSIONS: Tau expression and loss of alpha-tubulin and betaIII-tubulin expression were correlated with aggressive behavior in taxane-treated breast cancer. Further evaluation of Tau, alpha-tubulin and betaIII-tubulin may be useful in predicting clinical behavior and seeking therapeutic measures in taxane-based chemotherapy for breast cancer.

Fine Needle Aspiration Cytology of Thyroid Follicular Neoplasm: Cytohistologic Correlation and Accuracy

BACKGROUND: This study evaluated the accuracy of fine needle aspiration cytology (FNAC) in cases of follicular neoplasm (FN) on the basis of histologic diagnosis, and reviewed the cytologic findings of FN according to the FNAC. METHODS: Among the 66 cases diagnosed with thyroid FN by FNAC during the 7-year period from 2003 to 2009, 36 cases that had undergone thyroid surgery were available for review. Cytologic diagnosis was compared with the histologic diagnosis of each case. RESULTS: Among the 36 cases with a cytologic diagnosis of thyroid FN, histologic diagnosis was as follows: 20 follicular adenomas (55.6%), 3 Hurthle cell adenomas (8.3%), 2 follicular carcinomas (5.6%), 8 nodular goiters (22.2%), 2 papillary carcinomas (5.6%), and 1 Hashimoto's thyroiditis (2.8%), resulting in a diagnostic accuracy of FNAC for thyroid FN of 69.5%. CONCLUSIONS: This study shows that FNAC for thyroid FN is a useful primary screening method because when FN is diagnosed by FNAC, the rate of FN histologic diagnosis is relatively high, however, adequate sampling and experience is a prerequisite for this procedure.

Hedgehog Related Protein Expression in Breast Cancer: Gli-2 Is Associated with Poor Overall Survival

BACKGROUND: The hedgehog (Hh) signaling pathway is known to play a critical role in various malignancies, but its clinicopathologic role in breast cancer is yet to be established. METHODS: Tissue microarray blocks from 334 cases of breast cancer were prepared. The expression of six Hh signaling proteins including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene (Gli)-1, Gli-2, and Gli-3 were analyzed immunohistochemically. RESULTS: The expression of Hh signaling proteins was significantly correlated with some prognostic factors including the correlation of lymph node metastasis with the expression of Shh (p=0.001) and Ptch (p=0.064), the correlation of the stages with Shh and Gli-3 expression (p=0.007 and p=0.024, respectively), the correlation of the nuclear grade with the Smo (p=0.004) and Gli-3 (p=0.000), and the correlation of the histologic grade with the Ptch (p=0.016), Smo (p=0.007), and Gli-3 (p=0.000). The Shh, Ptch, Smo, Gli-1, and Gli-2 expression was significantly different between the phenotypes (p=0.000, p=0.001, p=0.004, p=0.039, and p=0.031, respectively). Gli-2 expression was correlated with a worse overall survival outcome (p=0.012). CONCLUSIONS: Hh pathway activation is correlated with a more aggressive clinical behavior in breast carcinomas. The comparison of phenotypes suggested that the Hh pathway may be a useful therapeutic target for breast carcinoma. Patients with Gli-2 expression had a significantly lower overall survival rate and, therefore, it showed promise as a prognostic marker.

A case of inflammatory myofibroblastic tumor originated from the greater omentum in young adult / 대한외과학회지

Inflammatory myofibroblastic (IMF) tumor is a rare solid tumor that often affects children. IMF tumors occur primarily in the lung, but the tumor may affect any organ system with protean manifestations. A 22-year-old woman was evaluated for palpable low abdominal mass that had been increasing in size since two months prior. Abdominal computed tomography showed a lobulated, heterogeneous contrast enhancing soft tissue mass, 6.5 x 5.7 cm in size in the ileal mesentery. At surgery, the mass originated from the greater omentum laying in the pelvic cavity and was completely excised without tumor spillage. Histologically, the mass was a spindle cell lesion with severe atypism and some mitosis. Immunohistochemistry for anaplastic lymphoma kinase-1 revealed that the lesion was an IMF tumor. Because of its local invasiveness and its tendency to recur, this tumor can be confused with a soft tissue sarcoma. Increasing physician awareness of this entity should facilitate recognition of its clinical characteristics and laboratory findings.

A Proposal for Creating a Guideline for Cancer Registration of the Fibromatosis, PEComa Group, Malignant Lymphoma In Situ and Dendritic Cell Tumors (III)

BACKGROUND: Understanding the biologic behavior of a tumor is a prerequisite for tumor registration code assignment. The aim of this report was to propose appropriate behavior codes of the International Classification of Disease Oncology 3 (ICD-O3) to rare, yet pathologically interesting hematopoietic and soft tissue tumors. METHODS: The Study Group for Hematopathology, the Bone and Soft Tissue Pathology Study Group, and the Cancer Registration Committee prepared the questionnaire containing provisional behavior codes of selected diseases. RESULTS: In situ lesions of mantle cell and follicular lymphomas, dendritic cell tumors, and neoplasms with perivascular epithelioid cell differentiation (PEComa), not otherwise specified were classified as malignant (-/3). The fibromatosis group, with the exception of lipofibromatosis, was proposed as benign (-/0). Lipofibromatosis and several diseases that belong to the PEComa group were proposed as uncertain malignant potential (-/1). For the hematologic and soft tissue tumors, 274 and 288 members of the Korean Society of Pathologists, respectively, provided opinions through questionnaire, and most responders showed agreement with the provisional behavior code proposed. CONCLUSIONS: The determination of behavior codes for the rare diseases described in this study, especially those of the PEComa group or malignant lymphoma, could be viewed as impractical and premature, but this study provides the basis for future research on this topic.

Review of atypical cytology of thyroid nodule according to the Bethesda system and its beneficial effect in the surgical treatment of papillary carcinoma / 대한외과학회지

PURPOSE: For the atypical cases of fine needle aspiration (FNA) cytology of thyroid nodules, ultrasonographic findings are a primary guideline for the surgical treatment. However, they have the intrinsic risk of overtreatment, as well. In this study we examined whether the Bethesda system could provide a real effect on the diagnostic rate of atypical cytology, and thereby reduce the number of cases diagnosed as atypical from FNA cytology. METHODS: We reviewed 166 cases diagnosed as atypical by FNA cytology at this institute between the years 2005 to 2010. We classified these cases on the basis of ultrasonographic and cytological findings and compared them with the histological results. RESULTS: Ultrasonographically, findings suspicious for malignancy and indeterminate were associated with 83.7% and 47.2% of malignancy rates, respectively. Cytopathologically, the malignancy rates varied according to the main cytological features and the highest malignancy rate was 77.3%. Based on the Bethesda system, 39.2% of the cases diagnosed as atypical could be grouped into the category of suspicious for malignancy and yielded a malignancy rate of 76.9%. CONCLUSION: Although ultrasonography provides an excellent guideline for the surgical treatment of atypical cases, it also showed considerable risk of overtreatment. The Bethesda system did not offer definitive effects on the rate of atypical cytology, but this system seemed to provide stricter boundaries for the atypical cytology and to aid in reducing the rates thereof. This in turn may permit that more limited cases are allotted to ultrasonographic decision making.

Pathologic Differences between Placentas from Intrauterine Growth Restriction Pregnancies with and without Absent or Reversed End Diastolic Velocity of Umbilical Arteries

BACKGROUND: Abnormal umbilical artery Doppler velocimetry is one of the important findings of intrauterine growth restriction (IUGR) and IUGR is associated with high perinatal morbidity and mortality. In addition, this abnormal Doppler velocimetry is correlated with placental insufficiency. The aim of this study was to determine the pathologic differences in the placentas from IUGR pregnancies with and without the absent or reversed end diastolic velocity (AREDV). METHODS: Among the cases that had undergone prenatal follow-up in our institute, a retrospective slide review was conducted for 18 cases of IUGR with AREDV and 17 cases with IUGR that had normal end-diastolic flow of the umbilical artery. RESULTS: The birth weight and the other clinical parameters were not different among the two groups. Grossly, the placental weight percentiles were significantly smaller in AREDV group when they were adjusted according to gestational age. Histologically, chronic deciduitis, mural hypertrophy of the decidual arteries, an intimal fibrin cushion of the large fetal vessels, increased syncytial knots, villous agglutinations, avascular villi, villous stromal-vascular karyorrhexis, and acute atherosis were more frequently found in the AREDV group and their presence showed statistical significance. CONCLUSIONS: These findings suggest that pathologic abnormalities due to fetal and maternal vasculopathies in the placenta may be the cornerstone for inducing AREDV in the umbilical artery.

Distribution of Dendritic Cells and Regulatory T-Cells in Cutaneous Lymphomas

BACKGROUND: Dendritic cells (DCs) play an important role in immune reactions. This study was designed to identify the distribution patterns of DCs and regulatory T-cells (Tregs) in cutaneous lymphomas. METHODS: Immunohistochemistry was used to determine langerin expression on Langerhans cells, CD11b on inflammatory DCs, CD209 and CD11c on dermal DCs, CD303 on plasmacytic DCs, and Foxp3 on Tregs in 81 cases of cutaneous lymphomas. RESULTS: Various DCs and Tregs were identified in most cutaneous lymphomas. Plasmacytic DCs, inflammatory DCs and Tregs were identified mainly in tumor areas, whereas dermal DCs were distributed both in the tumor and stromal areas. Among DCs, dermal DCs were most prominently identified in the cutaneous lymphomas not only in the tumor area but also in the stroma. The intense stromal infiltration of dermal DCs was consistent finding in T-cell lymphomas. Diffuse large B-cell lymphoma (DLBCL), not otherwise specified also showed intense stromal infiltration of dermal DCs, but stromal infiltration in DLBCL, leg type was relatively scant. CONCLUSIONS: The results suggest that all types of DCs and Tregs are involved in cutaneous lymphoma tumor immunity. Among them dermal DCs may play a dominant role.

Intussusception in an Adult due to Inverted Meckel's Diverticulum with Ectopic Pancreatic Tissue

Adult intussusception is rare involving of only 1% of the causes of bowel obstruction. We report a case of a 39-year-old female with intussusceptions due to inverted Meckel's diverticulum. She visited our hospital for diffuse abdominal pain during 1 week and aggravated abdominal pain for 2 days. Vital signs were stable, and there was periumbilical tenderness. She had no history of abdominal operation. CT scan showed a 3.7x2.1 cm of fatty mass with focal intussusception in the distal ileum. When the emergency operation was performed, the patient was found to be suffering from ileocolic intussusception. A manual reduction of intussusception showed inverted Meckel's deverticulum at 65 cm proximal to the ileocecal valve, and the segmental resection of small bowel including a Meckel's diverticulum was performed. Pathologic examination revealed a Meckel's diverticulum containing a 0.6x0.6 cm sized aberrant pancreas.

The Cytologic Features of Chronic Myelogenous Leukemia and Its Lymphoid Blast Phase in Body Fluid: A Case Report

Although chronic myelogenous leukemia (CML) may be involved in any part of the body, infiltration of the body fluid has rarely reported in the literature. Here we report on a 35 year-old male patient who was diagnosed chronic myelogenous leukemia ten years previously and he received allogenic hematopoietic stem cell transplantation. He then presented with left knee pain eight years after the initial diagnosis. MRI revealed a soft tissue mass at the distal femur. Cytology of the joint fluid revealed myeloblasts, promyelocytes, eosinophilic myelocytes, band neutrophils, megakaryocytes and orthochromatic erythroblasts, which was all consistent with leukemic infiltration of the knee joint fluid. The immunohistochemistry was positive for CD34, CD117 and myeloperoxidase (MPO). Despite that the patient underwent radiation therapy, MRI revealed growth of the mass, and ten months later, the lymphoid blast phase of CML was confirmed after biopsy. The patient received an above knee amputation. Five months later, multiple masses were revealed on PET-CT at the left iliopsoas muscle, abdominal wall and bones. Bilateral pleural effusion occurred shortly after this. Cytologic evaluation of the pleural fluid also revealed blast-like cells, and histologic evaluation of the abdominal mass confirmed the lymphoid blast phase of CML with positivity for CD3, UCHL-1, CD34 and CD117, but negativity for MPO.

Alteration of G1/S Cell Cycle Regulatory Proteins in Carcinogenesis of Cutaneous Squamous Cell Carcinomas

BACKGROUND: Aberration of the cell cycle regulatory proteins has been reported to contribute to the development and progression of human malignancy. We studied the expression of G1/S cell cycle regulatory proteins to investigate the carcinogenesis in cutaneous squamous cell lesions. METHODS: We evaluated the expressions of p16, pRb, cyclin D1 and Ki-67 protein by immunonohistochemistry in cases of normal skin (n=15), seborrheic keratosis (SK; n=26), actinic keratosis (AK; n=30), Bowen's disease (BD; n=37), keratoacanthoma (KA; n=23), and squamous cell carcinoma (SCC; n=22). RESULTS: The Ki-67 expression gradually increased from SK, through AK, to BD. The expression of p16 was more increased in BD than that in AK. The decreased expressions of p16 and Rb, and the increased expression of cyclin D1 were observed to a greater degree in SCC than those in BD. The expressions of cyclin D1 and Ki-67 were higher in SCC than those in KA. CONCLUSIONS: The altered expressions of p16, Rb, and cyclin D1 were considered to be related to the carcinogenesis in the cutaneous squamous cell lesions. Therefore, immunohistochemical studies of the cell cycle regulatory proteins and a combined analysis may be helpful as an adjunct to the histomorphology in the diagnosis of cutaneous squamous cell lesions.

The Cytology for Leukemic Cells in Cerebrospinal Fluid; Comparison of Conventional Cytology with Liquid-Based Cytology

BACKGROUND: The cytological examination of cerebrospinal fluid (CSF) using conventional cytology with a cytocentrifuge (cytospin) is an important method for evaluating the involvement of leukemia in the CNS. Liquid-based cytology (LBC) is now a widely used cytological method not only for gynecological and non-gynecological specimens, but its application to CSF for the identification of leukemic cell has not yet been reported. In this study, we tried to compare conventional cytology with using a cytospin with LBC and Papanicolaou (Pap) staining. We also examined the modified LBC with Wright staining to assess whether this modified method can be useful for diagnosing Leukemia. METHODS: We studied 30 cases of CSF that were obtained from 16 patients, including 17 cases of acute myeloid leukemia, 12 cases of acute lymphoblastic leukemia and 1 case of diffuse large B cell lymphoma. We applied conventional cytology with a cytocentrifuge (cytospin), LBC with Pap staining and modified LBC with Wright staining. RESULTS: The morphological features of the LBC with Pap staining showed difficulty for interpretation when compared with conventional cytology with a cytospin, and mainly because of cellular shrinkage. The modified LBC with Wright staining showed good morphological features. CONCLUSIONS: We suggest that modified LBC with Wright staining may be useful for examining CSF.

Mesenteric Fibromatosis Presenting as a Submucosal Tumor of the Jejunum

Mesenteric fibromatoses occur as sporadic lesions or as parts of familial adenomatous polyposis, are clonal lesions prone to locally aggressive behavior, but lack metastatic capacity. Fibromatoses harbor somatic beta-catenin or adenomatous polyposis coli (APC) mutations, leading to intranuclear accumulation of b-catenin. We report a case of mesenteric fibromatosis presenting as a 5.4x4.8 cm submucosal tumor of the jejunum in a 42-year-old woman. Histologically, the tumor consisted of proliferation of bland, elongated-spindle fibroblasts with collagen deposition and a characteristic prominent vasculature. Immunohistochemically, the tumor cells showed nuclear staining for beta-catenin. Mesenteric fibromatosis should be included in the differential diagnosis of submucosal spindle cell tumors of the gastrointestinal tract, and nuclear immunoreactivity for beta-catenin may help distinguish these tumors form histological mimics.

IgA Nephropathy Encountered in a Patient with Hodgkin Lymphoma / 대한신장학회지

Various types of glomerulonephritis can occur at the same time with Hodgkin lymphoma, including minimal change disease and membranous glomerulonephritis. However, the concurrence of IgA nephropathy with Hodgkin lymphoma is rare. We report here on a case of IgA nephropathy in a patient with newly diagnosed Hodgkin lymphoma: A 60-year-old man presented with weight loss and anorexia. The patient showed lymphadenopathies in the neck on physical examination, and multiple lymphadenopathies in the mediastinum and abdomen on computerized tomography. Diagnosis of Hodgkin lymphoma was made after cervical lymph nodes were excised, but during the course of the chemotherapy, laboratory findings of hematuria and an elevated creatinine level were observed and IgA nephropathy was additionally diagnosed from a renal biopsy. There were fluctuations in the creatinine level and the amounts of hematuria and proteinuria, but by the time of the eighth cycle of chemotherapy, the patients condition had rapidly deteriorated, mainly due to the newly developed adult respiratory distress syndrome. The patient died soon thereafter.

Gangliocytic Paraganglioma of the Duodenum

Gangliocytic paragangliomas are rare benign neuroendocrine tumors that arise mainly in the duodenum. A total of 3 cases of duodenal gangliocytic paraganglioma have been reported in Korea. The authors encountered another case of a gangliocytic paraganglioma in the duodenum. A 48-year old man presented with a mass in the duodenum that had been found incidentally in a medical checkup. The endoscopic examination revealed a 3.5x2.2 cm sized polypoid mass in the second portion of the duodenum. The patient underwent a polypectomy in the form of a wedge resection under general anesthesia. Microscopically, the tumor was composed of epithelial cells forming paraganglioma like patterns, spindle cells and ganglion cells. Gangliocytic paragangliomas are believed to be benign tumors but regional lymph node metastasis and recurrence can occur in rare cases. During the 27-month follow-up after treatment, there was no evidence of recurrence or lymph node metastasis. We report this case to help improve the understanding of this rare disease.

Concurrence of Spatially Separated Medullary Carcinoma and Papillary Carcinoma of the Thyroid Gland: A Report of Three Cases

Although medullary thyroid carcinoma (MTC) may coexist with papillary thyroid carcinoma (PTC) as a collision tumor within the same nodule or as two or more spatially separated tumors, these two carcinomas rarely coexist. We encountered three cases of sporadic MTCs spatially separated from PTCs, which occurred concurrently, either within the same thyroid lobe or in different thyroid lobes. In each of the cases the patients underwent total thyroidectomy and neck dissection. PTC metastases of the lymph node were observed in two of the cases and MTC metastasis of the lymph node was observed in one case. Among the multiple thyroid nodules affected by both MTCs and PTCs, only the dominant nodules had spread to the lymph nodes. Because MTC has a different clinical significance from PTC, in patients with multiple thyroid nodules, appropriate diagnostic approaches, such as fine needle aspiration of all possible nodules and measurement of serum calcitonin level, should be performed.

Touch Imprint Cytology Contributed to the Frozen Section Diagnosis of Merkel Cell Carcinoma : A Case Report / 대한세포병리학회지

Merkel cell carcinoma (MCC), a rare primary cutaneous small cell neuroendocrine carcinoma, is a tumor with distinct cytological features. In many cases, immunohistochemical staining (IHC) is required for the differentiation from other small round cell malignancies. Here we describe the cytological findings of Merkel cell carcinoma; these findings contributed to the diagnosis prior to performing IHC. A lower eyelid mass was excised and submitted for frozen section diagnosis. The frozen section diagnosis was consistent with a malignancy, but the more specific diagnosis was limited by the lack of specific histological features. Touch imprint cytology revealed a high cellularity with loosely cohesive small to large sized cells. The tumor cells showed hyperchromatic nuclei with fine chromatin and inconspicuous nucleoli, and thin-rimmed-cytoplasm including the characteristic eosinophilic button-like paranuclear inclusion, previously described as a pathognomonic cytological finding of MCC; this was not found in the H&E frozen section. In conclusion, we suggest that the touch imprint cytology may help in the differential diagnosis of small round cell neoplasms prior to performing IHC especially in frozen section diagnosis.

Pathological Findings of Crohn's Disease in the Stomach

BACKGROUND: The incidence of Crohn's disease in the upper digestive tract, and especially in the stomach, is recently increasing. Focal inflammatory reaction without Helicobacter pylori (H. pylori) infection is thought to be the characteristic pathologic findings suggesting Crohn's disease in the stomach. Yet gastric involvement of Crohn's disease has not been studied in Korea. We studied the endoscopic and pathologic findings of patients with Crohn's disease in the stomach by taking biopsies. METHODS: Thirty patients with Crohn's disease who underwent gastroduodenoscopy followed by biopsies were included in the study. The pathology of the gastric biopsy specimens and the presence of H. pylori were evaluated. RESULTS: Among 30 cases, 22 cases (73.3%) were H. pylori negative and 8 cases (26.7%) were H. pylori positive. For the H. pylori negative cases, all but one cases showed pit abscess and focal lymphocytic collections in the antrum. Granulomas were found in 6 cases (20%) and they were exclusively located in the antrum. CONCLUSIONS: In the stomach, pit abscess and focal lymphocytic collections that are not associated with H. pylori infection are the characteristic pathologic findings found in Crohn's disease.