Naomi Katsuki

Epidermoid Cyst in an Intrapancreatic Accessory Spleen: Three Case Reports and Review of the Literatures

The development of an epidermoid cyst in an intrapancreatic accessory spleen is an extremely rare lesion, with only 17 cases being reported in the English literature. All such cases were located in the pancreatic tail, some of which showed carbohydrate antigen 19-9 (CA19-9) immunoreactivity in the lining of the epithelium. A few of them indicated an elevation of the serum CA19-9 level. Here we report three cases of an epidermoid cyst in an intrapancreatic accessory spleen. Cases 1 and 2 were 57-year-old and 70-year-old women, while case 3 was a 37-year-old man. All three cases were asymptomatic. Serum CA19-9 levels showed within normal limits (case 1), slightly elevated (case 2), and clearly elevated (case 3). They underwent a distal pancreatectomy with splenectomy (cases 1 and 2) and without splenectomy (case 3). Grossly, the surgical specimen was a well-demarcated, multiple (case 1) or solitary (cases 2 and 3) cystic mass in the pancreatic tail. A high level of fluid CA 19-9 was detected in case 1. Microscopically, the cystic walls were lined with squamous and cuboidal epithelium, which were surrounded by normal splenic tissue and hyalinized fibrous tissue. The lining squamous epithelium was revealed as nonkeratinizing (Cases 1and 2) or keratinizing (Case 3). Immunohistochemically, CA19-9 was positive in the monolayer and surface layer of the cuboidal epithelium, but negative for the keratinizing squamous epithelium. As for the histogenesis, it is suggested that the cystic lining of the epithelium may derive from the pancreatic duct which protrudes into the accessory spleen.

Cytological findings of mixed squamous cell and glandular papilloma in the lung

Pulmonary mixed squamous cell and glandular papilloma is an extremely rare neoplasm. This is the first cytological report of such a rare neoplasm. A 59‐year‐old Japanese man was admitted to the hospital complaining of a persistent cough and bloody sputum. A bronchial endoscopic examination revealed an endobronchial polypoid tumor. Upon bronchial brush cytology by Papanicolaou stain, squamous dysplasia showing mild atypia was suspected. The smears showed moderate cellularity with singly scattered cells or loose clusters of cells, consisting of squamous cells and a few columnar cells. Nuclei of the squamous cells showed mild atypia, but there was no nuclear atypia of the columnar cells. Upon intraoperative pathological examination by frozen section, pulmonary mixed squamous cell and glandular papilloma was suspected. Intraoperative imprint cytology by Ultrafast Papanicolaou stain showed a few differences in comparison with bronchial brush cytology, which were thought to be due to differences in obtaining cytological specimens or the steps prior to the staining. The patient underwent a segmentectomy of the left lung. Histopathological diagnosis confirmed a mixed squamous cell and glandular papilloma. The postoperative course has been uneventful for 5 years after surgery. It was thought that cytology was diagnostically inadequate on its own in the present case. However, mixed squamous cell and glandular papilloma must be considered as another type of pulmonary tumor in cytological preparations, especially in a case showing endobronchial papillary growth by bronchoscopy. Diagn. Cytopathol. 2010;38:913–917.

Tumor Spread Through Air Spaces Is an Independent Predictor of Recurrence-free Survival in Patients With Resected Lung Squamous Cell Carcinoma

Tumor spread through air spaces (STAS) is a newly recognized pattern of invasion in lung adenocarcinoma. However, clinical significance of STAS has not yet been characterized in lung squamous cell carcinoma. In this study, we investigated whether STAS could determine clinical outcome in Japanese patients with lung squamous cell carcinoma. We reviewed tumor slides from surgically resected lung squamous cell carcinomas (n=216). STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. Tumors were evaluated for histologic subtypes, tumor budding, and nuclear diameter. Recurrence-free survival (RFS) was analyzed using the log-rank test and the Cox proportional hazards model. Tumor STAS was observed in 87 patients (40%), increasing incidence with lymph node metastasis (P=0.037), higher pathologic stage (P=0.026), and lymphatic invasion (P=0.033). All cases with STAS showed a solid nest pattern. The 5-year RFS for patients with STAS was significantly lower than it was for patients without STAS in all patients (P=0.001) and in stage I patients (n=134; P=0.041). On multivariate analysis, STAS was an independent prognostic factor of a worse RFS (hazard ratio=1.61; P=0.023). Patients with STAS had a significantly increased risk of developing locoregional and distant recurrences (P=0.012 and 0.001, respectively). We found that tumor STAS was an independent predictor of RFS in patients with resected lung squamous cell carcinoma, and it was associated with aggressive tumor behavior.

Cytopathologic features of orbital intraosseous chordoid meningioma: Report of a case and distinction from other myxoid/mucoid tumors

Chordoid meningioma (CM) is characterized by a striking histologic resemblance to chordoma and propensity for aggressive behavior or recurrence (WHO grade II designation). Orbital intraosseous CM is extremely uncommon and only one case report has been documented. A case is presented here in which squash smears of a left orbital tumor in a 53‐year‐old male revealed small clusters or cord‐like structures of bland tumor cells embedded in a myxoid or mucinous background. Whorl‐like structures were also identified. The tumor cells possessed uniformly round nuclei with a smooth nuclear outline, fine granular chromatin, and small nucleoli. Occasional intranuclear inclusions, coarse collageneous cytoplasmic filaments were observed. Many spindle‐shaped cells with similar nuclear findings were also seen. A cytologic diagnosis of a chordoid meningioma was suggested and histochemical and immunohistochemical studies were conducted on formalin‐fixed, paraffin‐embedded material. Immunohistochemically, the tumor cells showed diffuse and strong membranous and cytoplasmic staining for vimentin, epithelial membrane antigen (EMA) and faintly reactive with S‐100 protein but negative for pan‐neuroendocrine markers (i.e., NSE, chromogranin A, synaptophysin), cytokeratin AE1/AE3, smooth muscle actin, D2‐40, brachyury or class III beta‐tubulin. The proliferative index with MIB‐1 was less than 1%. The diagnosis of orbital intraosseous CM was confirmed based on cytopathologic, histopathological, immunohistochemical results, location of the tumor, and the lack connection to the duramater. We demonstrated here for the first time the cytopathological features of intraosseous CM with emphasis on differential diagnostic considerations. Diagn. Cytopathol. 2010; 38:818–821.

Cytopatholologic features of gliosarcoma with areas of primitive neuroepithelial differentiation of the brain in squash smears

Gliosarcoma with areas of primitive neuroepithelial differentiation (GSPNED) is an extremely rare neoplasm. A case is presented here in which squash smears of a left temporal lobe tumor in a 76‐year‐old male demonstrated two distinct and easily recognizable cellular populations, i.e., densely hyperchromatic cells of a primitive nature in a fibrillary background and pleomorphic spindle‐shaped cells. Occasional pseudo‐rosette formations and nuclear cannibalism suggestive of neuroendocrine differentiation were also found. A cytologic diagnosis of a malignant tumor was suggested, and histochemical and immunohistochemical studies were conducted on formalin‐fixed, paraffin‐embedded material. Reticulin stain highlighted increased intercellular collagen and reticulin deposition within the spindled regions, whereas nodules with primitive cells were reticulin‐poor. There was a diffuse and strong reactivity to neuron specific enolase, synaptophysin and CD56 immunostains. A stain for glial fibrillary acidic protein and S‐100 protein demonstrated a subset of tumor cells including elongated cytoplasmic processes. The spindled component was positive for vimentin and smooth muscle actin, whereas the primitive‐appearing tumor cells were negative. The diagnosis of GSPNED was confirmed based on cytopathologic, histopathological and immunohistochemical results. The cytomorphologic features of this distinctive tumor are illustrated, and the adjunctival value of squash smears for frozen‐section diagnosis is also discussed. This is the first presentation of a cytopathologic analysis that provides an important clue to an accurate diagnosis of GSPNED. Diagn. Cytopathol. 2009.

A Grading System Combining Tumor Budding and Nuclear Diameter Predicts Prognosis in Resected Lung Squamous Cell Carcinoma.

For lung squamous cell carcinomas, there are no histologic findings that have been universally accepted as prognostic factors. Tumor budding and nuclear grade have been recognized as prognostic factors in other carcinomas. In this study, we investigated whether pathologic findings could determine clinical outcome in Japanese patients with lung squamous cell carcinomas. Tumor slides from surgically resected lung squamous cell carcinomas (1999 to 2012) were reviewed (n=216). Tumors were evaluated for histologic subtypes, differentiation, tumor budding, nuclear diameter, and mitosis. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the log-rank test and the Cox proportional hazards model. Tumor budding and large nuclei were independent prognostic factors of a worse RFS (P<0.001 and P=0.002, respectively) and a worse OS (P<0.001 and P=0.038, respectively) on multivariate analysis after adjustment for pathologic stage and lymphatic invasion. However, histologic subtypes, differentiation, and mitotic count did not correlate with prognosis. A grading system combining tumor budding and nuclear diameter was an independent prognostic factors of a worse RFS (grade 2 vs. 1, hazard ratio [HR]=2.91; P<0.001, and grade 3 vs. 1, HR=7.60, P<0.001) and a worse OS (grade 2 vs. 1, HR=2.15; P=0.014, and grade 3 vs. 1, HR=4.54, P<0.001). We found that a grading system combining tumor budding and nuclear diameter was a significant prognostic factor among Japanese patients with resected lung squamous cell carcinoma.

IL-17A induces heterogeneous macrophages, and it does not alter the effects of lipopolysaccharides on macrophage activation in the skin of mice

Macrophages are central to inflammatory response and become polarized towards the M1 or M2 states upon activation by immunostimulants. In this study, we investigated the effects of lipopolysaccharides (LPS) and interleukin (IL)-17A on the activation of macrophages in in vivo mouse skin. We examined whether macrophages are activated in the skin of imiquimod (IMQ)-treated mice, a model for IL-17A-induced psoriasis-like skin inflammation, and flaky-tail (Flgft) mice, a model for IL-17A-induced chronic atopic dermatitis-like skin inflammation. LPS and IL-17A independently increased the expression levels of iNOS, CX3CR1, CD206, phospho-STAT1 and phospho-STAT3 proteins in the skin of B6 mice, and the effects of LPS was not altered by IL-17A. The expression levels of these proteins were increased in the skin of IMQ-treated and Flgft mice. IL-17A neutralization increased the expressions of iNOS and phospho-STAT1 in the IMQ-treated skin, but it decreased the expressions of CD206 and phospho-STAT3 proteins in the skin of Flgft mice, suggesting that macrophages to change from the M2 to the M1 state in the skin of these mice. These results suggest that IL-17A is involved in the activation of macrophages that are in the process of adopting the heterogeneous profiles of both the M1 and M2 states.

Primary Dermal Melanoma Latent for More than 10 Years

Dear Editor: Primary dermal melanoma (PDM) has been described as a novel rare variant of melanoma that is confined to the dermis and/or subcutaneous tissue1,2. There have been no reports focusing on the duration of PDM so far. We report here a case of PDM for more than 10 years. A 54-year-old Japanese woman was presented with an asymptomatic nodule on her sacral region. It had been present for more than 10 years. Two years later, she visited us again, complaining that the lesion had been growing and was painful for the past two months. A physical examination revealed a brown/red, elastic hard, dome-shaped nodule measuring 18×18 mm in diameter (Fig. 1A). A histopathological examination revealed a solitary, well-circumscribed, dermal and subcutaneous nodule that was encapsulated by fibrous tissue with extensive central necrosis and hemorrhage (Fig. 1B). Immunohistochemistry (IHC) showed that the tumor cells were positive for S100 protein, Melan-A and HMB-45 (Fig. 2A). In addition, IHC for p53, cyclin D1 and Ki-67 (Fig. 2B) were low positive (8.0%, 14.7% and 14.9% of cells were positive, respectively). Moreover, negative staining for D2-40 was observed. Positron emission tomography and computed tomography revealed no evidence of another primary melanoma or metastatic lesions. We diagnosed her with PDM. Wide local excision with a 2 cm margin was performed again. Then, the patient received a course of DAV-feron therapy (dacarbazine, nimustine hydrochloride, vincristin sulfate and interferon-β), followed by several local injections of interferon-β. After 3 years of follow-up, there has been no evidence of recurrence or metastasis. Fig. 1 (A) Brown/red nodule on the sacral region. (B) Primary dermal melanoma composed of a dermal and subcutaneous nodule surrounded by fibrous tissue, with extensive central necrosis and hemorrhaging (H&E, ×10). Fig. 2 Immunohistochemical findings of primary dermal melanoma. (A) HMB-45 staining was focally positive (×200). (B) Ki-67 staining was low positive (14.9% of cells were positive) (×200). Clinically, PDM may be misdiagnosed due to its features, which resemble a cyst or subcutaneous nodule. Histopathologically, it is difficult to differentiate PDM from solitary cutaneous metastatic melanoma. Recently, low levels of p53, Ki-67, cyclin D1 and D2-40 unique to PDM have been proposed2. Our findings were concordant with them. Central necrosis and hemorrhage were seen in our case. Of course these features may be the reflection of traumatized melanocytic nevus; moreover, these features are also frequently observed in PDM2. Furthermore, characteristic changes indicative of traumatized melanocytic nevus, such as ulceration, parakeratosis and less than 5% of Ki-67 labeling, were not recognized in our case. According to the 2009 American Joint Committee on Cancer (AJCC) melanoma staging guidelines, localized metastases to the skin or subcutaneous tissues with an unknown primary site are defined as stage III, although they are classified as stage IV (M1a) according to the 2002 AJCC melanoma staging database3. The five-year survival rate of stage IIIB (T1-4aN2cM0) melanoma is 59%3. In contrast, the Kaplan-Meier 8-year survival rate of PDM was 83% in one series1 and 92% at a mean follow-up duration of 44 months in another2. Thus, patients with PDM achieve markedly better survival compared to metastatic melanoma patients. Although we cannot deny the possibility of recent malignant changes from the preexisting melanocytic dermal nevus, it is worth noting that our case has more than 10 years of history. The disease duration of PDM was not mentioned in the previous 2 case series1,2. One Japanese case showed a 3-year history4. Long disease duration may be indicative of less aggressive behavior.

Antenatal ultrasonographic features of fetal capillary hemangioma in the posterior fossa

A capillary hemangioma with hydrocephalus in the posterior fossa of a fetus was detected on ultrasonography at 38 weeks and 4 days of gestation. A well‐defined, round tumor with a mixed pattern occupied the posterior fossa, and the normal cerebellum was significantly compressed by this tumor. No other anomaly was detected. Delivery was induced because of rapidly progressive hydrocephalus, and an otherwise healthy female infant weighing 2800 g was delivered vaginally at 39 weeks and 4 days of gestation. Histologic examination of the lesion through biopsy demonstrated capillary hemangioma. The tumor spontaneously decreased in size, and disappeared six months later. The child is now 2 years of age, and is developing normally.

Cytopathologic characteristics and differential diagnostic considerations of neuroglial heterotopia of the retropharyngeal space

Neuroglial heterotopias (NGH) are rare congenital head and neck lesions composed of differentiated neuroectodermal tissue and representing developmental heterotopias rather than true neoplasms. The case of a male neonate with respiratory distress and early feeding problems depicting a retropharyngeal space mass which in the intraoperative squash smears revealed glial cells with multiple cytoplasmic processes is reported here. Small clusters of cuboidal epithelial cells with rosette‐like ependymal structures and cuboidal cells arranged in sheets or branching folds suggestive of choroid plexus cells were also identified. Through this cytological approach a cytologic diagnosis of a NGH or low‐grade astrocytoma was suggested. Further evaluation and immunohistochemical studies were conducted on formalin‐fixed, paraffin‐embedded material. Glial cells, ependymal structures and choroid plexus were identified on H&E sections. Immunohistochemically, the glial cells showed diffuse and strong cytoplasmic staining for glial fibrillary acidic protein (GFAP) and S‐100 protein and focal immunoreactivity for synaptophysin and neurofilament. The proliferative index with MIB‐1 was around 4%. The diagnosis of NGH of the retropharyngeal space was confirmed based on the clinical, cytopathologic, histopathology, immunohistochemical results, and the location of the tumor. We demonstrated here for the first time the cytopathological features of NGH of the retropharyngeal space with emphasis on differential diagnostic considerations. Diagn. Cytopathol. 2011.