Sun Hee Sung

Acute Fibrinous and Organizing Pneumonia Following Hematopoietic Stem Cell Transplantation

A 60-year-old man presented with cough, sputum, and dyspnea. He had a history of acute myeloid leukemia and hematopoietic stem cell transplantation with chronic renal failure. Chest CT scans showed miliary nodules and patchy consolidations. Histological examination revealed numerous fibrin balls within the alveoli and thickening of the alveolar septum, both of which are typical pathological features of acute fibrinous and organizing pneumonia (AFOP). We report the first case of AFOP following allogeneic hematopoietic stem cell transplantation.

Chronic eosinophilic pneumonia associated with an initiation of rheumatoid arthritis

Although peripheral blood eosinophilia is observed in patients with active inflammatory rheumatoid arthritis (RA), RA is not a recognised cause of pulmonary eosinophilia. We describe a 55-year-old woman affected by chronic eosinophilic pneumonia (CEP) concomitantly with an initiation of RA. Both diseases responded rapidly and completely to high-dose corticosteroid therapy. In this patient, the initiation of RA and CEP was directly related, implying a common pathogenetic link between the two diseases.

A case report of crescentic glomerulonephritis associated with Hantaan virus infection

Although various glomerular diseases in hantavirus infection have been reported, an association between hantavirus infection and crescentic glomerulonephritis has not been described. Herein, we report a case of immune complex-mediated crescentic glomerulonephritis in a 70-year-old man with Hantaan virus infection.

Prognostic value of human apurinic/apyrimidinic endonuclease 1 (APE1) expression in breast cancer.

Human apurinic/apyrimidinic endonuclease 1 (APE1) is an essential protein for DNA base excision repair (BER) and redox regulation. The ability of cancer cells to recognize DNA damage and initiate DNA repair is an important mechanism for therapeutic resistance. Several recent studies have suggested that APE1 expression levels and/or subcellular dysregulation may be used to indicate the sensitivity of tumors to radiotherapy or chemotherapy. In this study, we assessed the prognostic significance of APE1 and differences in APE1 expression levels according to breast cancer molecular subtypes. We analyzed formalin-fixed, paraffin-embedded tumor tissue sections from 243 cases diagnosed as invasive breast cancer at Ewha Womans University Medical Center between January 2003 and December 2008. Immunohistochemistry was performed and the nuclear level of APE1 was scored by taking into account the percentage of positive cells. Medical records were reviewed to investigate clinicopathologic characteristics. We found that nuclear APE1 high-level expression (proportion ≥50%) in breast cancer showed a tendency towards unfavorable prognosis regarding disease-free survival (p = 0.093). However, there was no significant difference in overall survival between low and high-level expression groups (p = 0.294). Interestingly, within the Ki-67 low-level expression group, APE1 low-level expression was significantly associated with poor overall survival (p = 0.007). A significant positive correlation was observed between APE1 nuclear expression and estrogen receptor status (75.7% vs. 59.7%, p = 0.022). Also, the luminal A subtype was the most commonly observed breast cancer subtype in the APE1 high-level expression group (61.6% vs. 45.2%, p = 0.000). This study suggests that APE1 expression may be associated with breast cancer prognosis. In particular, its role as a prognostic factor would be significant for breast cancers with a low Ki-67 proliferation index. It is proposed that nuclear APE1 may be a novel target in breast cancer with a low proliferation rate to obtain better outcome.

Topoisomerase II alpha and microtubule-associated protein-tau as a predictive marker in axillary lymph node positive breast cancer.

Aims and Background The aims of this study were to investigate the correlation between topoisomerase II alpha (TOP2A), microtubule-associated protein-tau (MAPtau) and other prognostic factors in breast cancer and to evaluate the predictive value of TOP2A and MAP-tau in breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy. Methods and Study Design Seventy patients with axillary lymph node positive breast cancer who underwent curative surgery between January 2000 and December 2005 were evaluated retrospectively. The levels of protein expression of TOP2A and MAPtau were assessed using immunohistochemistry. Results Among the 70 patients, 43 (61.4%) showed TOP2A overexpression and 30 (42.9%) showed MAP-tau positivity. TOP2A overexpression was associated with p53 positivity and high histological grade. MAP-tau positivity was associated with a lower positive lymph node ratio, lower proliferative activity, and hormone receptor positivity. Based on the TOP2A and MAP-tau expression, there was no significant difference in disease-free survival in the breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy. Conclusions We conclude that immunohistochemical analysis of TOP2A and MAPtau protein expression may not predict the benefits of adjuvant anthracycline and taxane chemotherapy in axillary node positive breast cancer.

Unusual Expression of Thyroid Transcription Factor 1 and Napsin A in Metastatic Adenoid Cystic Carcinoma of Extrapulmonary Origin in the Lung

OBJECTIVES Our study examines thyroid transcription factor 1 (TTF-1) expression in 40 primary adenoid cystic carcinomas (ACCs) arising in various sites and compares TTF-1 expression between primary and metastatic ACCs in 12 cases with distant metastases. METHODS Forty patients with ACCs, including 12 pairs of primary and metastatic ACCs, were evaluated for the immunohistochemical expression of TTF-1 (clone SPT24). In addition, 10 metastatic ACCs to the lung were tested on napsin A and a different TTF-1 antibody (clone 8G7G3) for further evaluation. RESULTS No primary ACCs showed TTF-1 immunoreactivity (clone SPT24). TTF-1 was positive in five (41.7%) of 12 metastatic ACCs; all five cases were found only in the lung and comprised five (50.0%) of 10 cases. In all positive cases, staining was focal and detected only in the cribriform histologic subtype. Staining patterns using both antibodies (both SPT24 and 8G7G3) were very similar, and TTF-1-positive tumor cells were also positive for napsin A. Extrapulmonary ACCs were all negative for TTF-1 regardless of origination and metastasis. CONCLUSIONS TTF-1- and napsin A-positive ACCs in the lung should not be considered primary ACCs because TTF-1 and napsin A can be expressed in metastatic ACCs of the lung.

Expression of Cyclooxygenase-2 in Human Breast Cancer: Relationship with HER-2/neu and other Clinicopathological Prognostic Factors

PURPOSE Previous epidemiologic studies have demonstrated that nonsteroidal anti-inflammatory drugs can reduce the risk of breast cancer, and this possibly happens via cyclooxygenase (COX) inhibition. Moreover, growth factor-inducible COX-2, which is overexpressed in neoplastic tissue, is an attractive therapeutic target. Thus, we evaluated the expression of COX-2 in breast cancer tissues, and we assessed the association between COX-2 expression and HER-2/neu expression and also with several clinicopathological features. MATERIALS AND METHODS We analyzed the surgical specimens from 112 women with breast cancer who had undergone lumpectomy or mastectomy. The expressions of COX-2, HER-2/neu, MMP-2 and TIMP-2 were determined immunohistochemically. The correlations between COX-2 expression and several variables, including clinicopathological factors, HER-2/neu expression, MMP-2 expression and TIMP-2 expression were analyzed. Survival analysis was also performed with respect to COX-2 overexpression. RESULTS The overexpression of COX-2 protein was observed in 28.6% of the breast cancer tissues. Tumors with lymph node metastasis more frequently showed COX-2 overexpression than did those tumors without metastasis (p=0.039), and the increased COX-2 expression correlated positively with HER-2/neu overexpression (p=0.000). No significant differences were found for the MMP-2 or TIMP-2 expression rates in the COX-2 positive and negative groups. The survival analysis revealed no significant differences according to the COX-2 expression. CONCLUSION This study results suggest that increased COX-2 expression is related with the progression of breast cancer, e.g., with lymph node invasion. COX-2 overexpression found to be related with HER-2/neu overexpression, but not with MMP-2 or TIMP-2 expression. These results support the potential use of selective agents that inhibit COX-2 or HER-2/neu for the management of breast cancer.

Primary Adenosquamous Cell Carcinoma of the Pancreas: A Case Report with a Review of the Korean Literature

The most common pancreatic cancer is adenocarcinoma. Primary adenosquamous cell carcinoma of the pancreas is very rare and aggressive. A 46-year-old man presented with a 3-month history of dyspepsia and a 7-kg weight loss. The physical examination showed tenderness of the right upper quadrant of the abdomen. There was no jaundice. Amylase and lipase were elevated. CA 19-9 was elevated to 566.7 U/mL. Gastroduodenoscopy showed a hard ulceroinfiltrative mass with a yellowish exudate that bled readily on touch in the second portion of the duodenum. Abdominal computed tomography showed a 7.1 × 6.3-cm heterogeneously enhancing mass in the pancreatic head. The pancreatic mass had invaded the duodenum wall, gastric antrum, and gastroduodenal artery sheath. Fine-needle aspiration biopsy of the pancreatic mass revealed adenosquamous cell carcinoma, anaplastic type. We concluded that an adenosquamous cell carcinoma of pancreas had invaded the duodenal mucosa causing ulceration.

Expression patterns of GATA3 and the androgen receptor are strongly correlated in patients with triple-negative breast cancer.

GATA-binding protein 3 (GATA3) is a diagnostically useful immunohistochemical marker of breast cancer. Because of its strong association with estrogen receptor expression, GATA3 has markedly reduced sensitivity in triple-negative breast cancer (TNBC). We constructed a tissue microarray using a large series of TNBCs and evaluated GATA3 expression by TNBC subtype as defined by surrogate immunohistochemical markers. A total of 205 TNBCs were classified into cancers of the molecular apocrine type (n=23, 11.2%), claudin-low type (n=21, 10.2%), basal-like type (n=91, 44.4%), mixed type (n=62, 30.2%), and null type (n=8, 3.9%). The GATA3 scores (staining intensity × proportion) were categorized as negative (0), focally positive (1-10), or positive (11-300). GATA3 staining was negative in 153 cancers (74.6%), focally positive in 11 (5.4%), and positive in 41 (20.0%). The rate of focal positivity or positivity for GATA3 was significantly higher in the molecular apocrine type (73.9%, 17/23) than in other types of TNBCs (P=.001). The mean GATA3 score of molecular apocrine-type TNBC was significantly higher than that of the other types (P=.001) and differed significantly between androgen receptor (AR)-positive and AR-negative TNBCs (P<.001). In conclusion, GATA3 expression was correlated strongly with AR-positive, molecular apocrine-type TNBCs. Co-expression of AR and GATA3 is a specific feature of molecular apocrine-type TNBC, which may serve as a diagnostic aid for cancer of unknown primary.

A case of membranoproliferative glomerulonephritis associated with metastatic colon cancer

To the Editor, Glomerular diseases frequently develop in patients with malignancy. It has been reported that 11% of adult patients with nephrotic syndrome also have malignant tumors [1]. Previous data show an excess incidence of de novo cancer (5.2%) after diagnosis of renal diseases in patients with biopsy proven glomerulopathy, compared to the general population [2]. Membranous glomerulonephritis (MGN) is the most common malignancy related glomerular disease [3]. Although a few reports have described membranoproliferative glomerulonephritis (MPGN) in association with lung cancer [3], MPGN related to colon cancer has to our knowledge not yet been reported. Here, we present a case of rapidly progressive MPGN associated with metastatic colon cancer. A 58-year-old male patient was admitted to our hospital for his first chemotherapy session to treat metastatic sigmoid colon cancer. The patient had been diagnosed with sigmoid colon cancer with hepatic metastasis (stage IV, T4aN1bM1) 50 days earlier. Other past medical history was unremarkable. Sigmoidectomy with partial hepatectomy had been performed 40 days earlier. The pathological type was characterized as adenocarcinoma. He was referred to the nephrology department due to abruptly increased levels of blood urea nitrogen (BUN; 68 mg/dL) and serum creatinine (sCr; 2.2 mg/dL). His laboratory results were within the normal range 50 days earlier: BUN, 11 mg/dL; sCr, 1.0 mg/dL; and there was no proteinuria or hematuria on urinalysis. On day 1 of admission, he complained of nausea, vomiting, and poor oral intake. Blood pressure was 140/70 mmHg, pulse rate was 70 beats/min, and body temperature was 37.4℃. Bilateral pretibial pitting edema and moderate ascites were noted on physical examination. Laboratory studies revealed white blood cell (WBC) count 9,400/mm3, hemoglobin 10.5 g/dL, hematocrit 31.0%, platelet count 153,000/mm3, potassium 5.2 mEq/L, total protein 5.4 g/dL, albumin 2.5 g/dL, phosphorus 3.9 mg/dL, and total cholesterol 178 mg/dL. Urinalysis with microscopic examination showed urine protein (3+), a red blood cell count of 21 to 30/high power field (HPF) and a WBC count of 6 to 10/HPF. The spot urine protein/creatinine ratio was 19.9 and the fractional excretion of sodium was 0.62%. Twenty-four hour urine collection could not be performed due to a decreased urine output and poor patient cooperation. Urine protein electrophoresis showed nonselective glomerular proteinuria. Immunological studies showed no specific abnormalities. Antineutrophilic cytoplasmic antibody, antinuclear antibody, and antiglomerular basement membrane antibody were negative. Serologic markers of hepatitis B and hepatitis C were negative. The carcinoembryonic antigen level was decreased compared with the value at diagnosis (5.7 ng/mL vs. 163.9 ng/mL). Urine cytology revealed negative results. Abdominal sonography showed normal sized kidneys with appropriate echogenicity. Ascitic fluid analysis revealed transudate with no abnormal cells. On day 4 of admission, a kidney biopsy was performed because his renal function did not improve. Upon light microscopic examination, glomerular enlargement due to diffuse endocapillary proliferation, diffuse thickening of capillary loop with double contour, subendothelial and mesangial fuchsinophilic deposition, and glomerular neutrophil infiltration were found. Cellular crescents were found in four of 24 glomeruli. Mild tubular atrophy, interstitial edema, fibrosis, and mild neutrophilic and mononuclear cellular infiltrations were found. Immunofluorescence microscopy showed immunoglobulin G (IgG), IgA, C1q, dominant C3, fibrinogen, and mild IgM, as well as C4 deposition in both the mesangium and capillary loops. These findings were compatible with type 1 MPGN (Fig. 1). Chemotherapy was delayed due to the poor general condition of the patient. On day 12 of admission, hemodialysis was initiated because BUN and sCr levels were elevated to 57 and 4.2 mg/dL, respectively. His uremic symptoms, including nausea, and vomiting were aggravated, and daily urine output was < 500 mL. On day 20 of admission, the first chemotherapy session was performed with FOLFOX (oxaliplatin, leucovorin, and 5-fluorouracil). After that, four more cycles of FOLFOX chemotherapy were performed at intervals of 2 weeks. Follow-up abdominopelvic computed tomography at 3 months showed no evidence of recurrence of primary cancer. The patient is currently undergoing maintenance hemodialysis three times per week. Figure 1 (A) A glomerulus showing a membranoproliferative pattern of injury. There was hypercellularity due to diffuse mesangial and endocapillary proliferation with neutrophilic infiltration (periodic acid-methenamine silver stain, × 400). Capillar y ... Various glomerular diseases such as MGN and minimal change disease frequently present as a paraneoplastic syndrome in different solid or hematological malignancies. Although there are some case reports of MPGN associated lung cancer or renal cell carcinoma [3], MPGN associated solid organ malignancy has rarely been reported. The mechanisms that underlie how malignancy induces renal diseases remain unresolved. Three hypotheses have been suggested to explain the pathogenesis of tumor associated glomerulonephritis: 1) an undiagnosed malignancy associated with antigen deposition may have caused glomerular disease-like paraneoplastic syndrome; 2) immunosuppressive therapy used in glomerular disease may trigger tumorigenesis; and 3) viral infection may have induced both glomerulopathy and cancer by: intrinsic viral oncogenic activity; disrupted renal clearance of biological mediators associated with oncogenesis; or both [2]. The treatment of MPGN depends in part upon the underlying cause because most cases appear to have an identifiable chronic disease with circulating immune complexes [4]. However, there are limitations in proving the effectiveness of immunosuppressive drugs in progressive MPGN. Furthermore, the development of severe nephrotic syndrome, renal insufficiency, hypertension at presentation, and negative findings of renal biopsy (formation of crescents and tubulointerstitial disease) are known as poor prognostic factors [5]. We did not administer any immunosuppressive agents to our patient because he was considered to have a low probability of renal recovery, despite treatment of MPGN itself, and he was at higher risk due to his poor general condition. In this patient, amelioration of renal function after cancer excision and chemotherapy was not observed. Based on this finding, we cannot rule out a coincidental association of MPGN with colon cancer. However, remnant metastasis may have been present, although the macroscopic masses were removed by surgery. Nevertheless, cytotoxic therapy was not performed due to age, poor general condition, drug toxicity, and low life expectancy. Other glomerular diseases such as crescentic glomerulonephropathy or acute tubular necrosis (ATN) were possible causes of the aggravated renal function. However, the pathology showed that the crescentic lesions comprised < 50% of the total and no findings compatible with ATN were identified. If ATN was the cause of the renal dysfunction, renal function should have recovered after conservative treatment. However, his renal function remains exacerbated. These findings suggest that renal failure in this patient was caused by rapid progress of glomerulopathy associated malignancy. In addition, there were no additional etiologies to explain the development of MPGN. Therefore, we believe that colon cancer may have contributed to the development of MPGN in our patient, in part, because the development of idiopathic MPGN in a relatively elderly individual is uncommon. We report here a case of rapidly progressive MPGN associated with metastatic colon cancer.