Moderate Cellular Atypia Research Articles

Basaloid Squamous Cell Carcinomas of the Thymus With Prominent B-Cell Lymphoid Hyperplasia: A Clinicopathologic and Immunohistochemical Study of 10 Cases.

Ten cases of basaloid squamous cell carcinomas of the thymus are presented. The patients are 6 women and 4 men ranging in ages between 51 and 72 years (average: 61.5y), who presented with nonspecific symptoms of cough, dyspnea, and chest pain with no history of malignancy, myasthenia gravis, or other autoimmune disease. Surgical resection of the mediastinal masses via thoracotomy or sternotomy was performed in all patients. Grossly, the tumors varied in size from 2 to 8cm, were light tan in color, solid and slightly hemorrhagic, and had infiltrative borders. Histologically, scanning magnification showed elongated interanastomosing ribbons of tumors cells embedded in a lymphoid stroma containing germinal centers. At higher magnification, the tumors cells were round to oval with moderate amounts of lightly eosinophilic cytoplasm, oval nuclei, moderate cellular atypia, and mitotic activity ranging from 3 to 5 mitotic figures per 10HPFs. In 8 cases, the tumor invaded perithymic adipose tissue, in 1 case the tumor infiltrated pericardium, and in 1 case, the tumor involved the pleura. Immunohistochemical stains showed positive staining in the epithelial component for pancytokeratin, p63, keratin 5/6, and p40, while CD20 and CD79a characterized the lymphoid component. Clinical follow-up was obtained in 7 patients. Two patients died within 24 months and 5 patients remained alive between 12 and 60 months. The current cases highlight the unusual feature of B-cell lymphoid hyperplasia in these tumors and their potential aggressive behavior.

Primary follicular dendritic cell sarcoma of the pleura: A clinicopathological and immunohistochemical study of two cases

Two cases of primary follicular dendritic cell sarcoma (FDCS) of the pleura are presented. The patients are a woman 76-years-old and a man 64-years-old who presented with nonspecific symptoms including chest pain, dyspnea, and cough. Clinical history did not disclose any pertinent history of previous malignancy. Diagnostic imaging showed the presence of a pleural-based mass in both patients and a thoracotomy with resection of the pleural mass was performed. Both tumors were described as solid, light tan, and with ill-defined borders. Histologically, both tumors showed similar histological features, namely the presence of a spindle cellular proliferation composed of elongated cells with fibrillary cytoplasm, oval nuclei, and conspicuous nucleoli. Mild to moderate cellular atypia was present, while mitotic figures ranged from 3 to 4 per 10 high power fields. Mature lymphocytes and plasma cells were also present dispersed throughout the tumor. Immunohistochemical stains in both cases show positive staining for CD21 and CD35 while focal staining was present for D2-40 and clusterin, while negative for other markers including keratin, desmin, S-100 protein, calretinin, and STAT-6. Clinical follow up shows that both patients have remained alive 12 and 14 months after initial diagnosis. The cases herein described represent an unusual occurrence of FDCS arising in the pleural surface and one that must be kept in mind when dealing with spindle cell tumors of the pleura.

Polycythemia Vera: New Diagnostic Concept and Its Types

Polycythemia vera (PV) is a clonal Ph-negative myeloproliferative disorder characterized by excessive myeloid proliferation of three hematopoietic cell lineages leading to ineffective myelopoiesis. According to WHO classification (2008), hemoglobin and hematocrit values are listed among the major diagnostic criteria. However, in many PV patients the levels may be below the diagnostic level, thus leading to underdiagnosis of PV. At present, three clinical types of the disease are recognized: 1) masked (latent/prodromal), 2) classic (overt), and 3) PV with progression/transformation into myelofibrosis. The masked form is most difficult for diagnosis, being highly heterogeneous with regard to clinical manifestations, laboratory data, medical history, and the course of the disease. It includes early stages, some of them with very high platelet count, imitating essential thrombocythemia, cases with abdominal thrombosis, and latent PV. Bone marrow trephine biopsy appears to be the most reliable method for diagnosis of masked PV. Findings typical for PV are readily visible, including hypercellular bone marrow with three-lineage myeloid proliferation, excess of megakaryocytes with mild to moderate cellular atypia and polymorphism. Grading of reticulin fibrosis has impact on prognosis and reflects the risk of progression into myelofibrosis. In revised edition of WHO classification (2016), the typical bone marrow histopathology will be included among the major criteria for the diagnosis of PV, meaning that bone marrow trephine biopsy is a mandatory diagnostic procedure in patients with borderline levels of hemoglobin and hematocrit.

Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions

ObjectivesIn most prostate biopsies, the seminal epithelium is easily recognized because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyze the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. MethodsWe consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. ResultsThirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. ConclusionsThe seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies.

El epitelio seminal en biopsia prostática puede semejar lesiones prostáticas malignas y premalignas

ObjectivesIn most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. MethodsWe consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. ResultsThirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. ConclusionsThe seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies.

Neonatal streptozotocin treatment causes type 1 diabetes and subsequent hepatocellular carcinoma in DIAR mice fed a normal diet.

Hepatocellular carcinoma (HCC) represents a major health challenge because of its increasing morbidity and mortality. The establishment of useful models of HCC can significantly contribute to unveiling its pathophysiology. We developed a novel mouse model of HCC based on type 1 diabetes and reported its histopathological features. Newborn male ddY, Institute for Animal Reproduction (DIAR) mice were divided into two groups on the basis of streptozotocin treatment, which induces type 1 diabetes. Streptozotocin was subcutaneously injected (60mg/g) into the treated group (DIAR-nSTZ mice), whereas physiologic solution was injected into the control group (DIAR-control mice) at 1.5days after birth. All mice were fed a normal diet and histopathologically assessed at 6, 8, 10, 12, 19, and 27weeks of age. At 8weeks, small hepatocytic nodules with mild to moderate cellular atypia were observed in the livers of DIAR-nSTZ mice, which progressed to large hepatocytic nodules with cellular atypia and infiltrating growth at 12weeks, identical to those in well-differentiated human HCC. At 19 and 27weeks, moderately differentiated HCC was observed in all DIAR-nSTZ mice. Conversely, no neoplastic findings were evident in DIAR-control mice. No steatosis or fibrosis was evident in either group. Immunohistochemical analysis revealed that all nodules observed in DIAR-nSTZ mice were positive for glutamine synthetase. In DIAR-nSTZ mice, the development of HCC with similarity to human HCC and high reproducibility can be achieved using a short and simple protocol. We believe that this model will be useful for studying liver carcinogenesis.

Atypical choroid plexus papilloma: a case report and literature review

Objective To report a rare case of atypical choroid plexus papilloma and explore its clinical presentations and histopathological features, at the same time to take a review of relevant literature. Methods and Results A 1 ⁃ year ⁃ old male patient presented with vomiting for 3 days after a sudden tumbling. Computed Tomography (CT) showed a space⁃occupying lesion located in the left lateral ventricle. The lesion was with slight hyper⁃intensity signal compared to the adjacent brain parenchyma. Left lateral ventricle was enlarged and hydrocephalus was visible. Besides, edema occured in adjacent cerebral tissues. The surgical operation was performed under general anesthesia. During the operation, the tumor tissue was in heterogeneous consistency and rich blood supply, showing grey⁃white color, and attached to the choroid plexus. Microscopically, most tumor cells grew around the fibrovascular axis forming papillary pattern and showed no obvious atypia. However, in some areas, solid and sheet⁃like patterns were identified. Within these areas, increased cell density, mild to moderate cellular atypia and focal necrosis were appreciated. Some cells with acidophilic cytoplasm, few giant tumor cells and accidental mitosis were also seen, and the counting of mitosis was 2/10 HPF. Immunohistochemistry showed positive expression of pancytokeratin (PCK), synaptophysin (Syn), cytokeratin (CK)8/18, vimentin (Vim) and podoplanin (D2⁃40) in tumor cells. Integrase interactor⁃1 (INI⁃1) were also positively and focally expressed. The Ki⁃67 labeling index of tumor cells was 8％ . S ⁃ 100 protein, CK19, neuronal nuclei (Neu ⁃ N), glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), chromogranin A (CgA), CK7 and CK20 were negatively stained. The patient was followed up for 6 months after operation and no recurrence was found. Conclusion Atypical choroid plexus papilloma, the biological behavior of which is between benignancy and malignancy, is one of the rare tumors of central nervous system that occurs in the ventricular system. The incidence is low. It often occurs in the early childhood with atypical histopathological features. Follow up is suggested although patients with complete resection usually have a good long⁃term prognosis. DOI：10.3969/j.issn.1672⁃6731.2012.06.017

Metastatic Ductal Adenocarcinoma in a Western Hognose Snake (Heterodon nasicus)

A 17-yr-old Western Hognose snake (Heterodon nasicus) presented with a prominent midcoelomic swelling. Surgical exploration revealed a large, multicystic, irregular, tan, and firm mass grossly effacing the splenopancreas. The mass was subsequently removed. Histologically, the mass was composed of tubules of columnar to flattened neoplastic cells with an abundant stroma and moderate cellular atypia consistent with a scirrhous adenocarcinoma, likely ductal in origin, given the location of the neoplastic mass. Bloodwork revealed anemia, monocytosis, marked hypercalcemia, and, postoperatively, persistent hyperglycemia. After postoperative recovery, the snake was diagnosed with iatrogenically induced diabetes mellitus and exocrine pancreatic insufficiency. Due to the inability to clinically control the diabetes mellitus and exocrine pancreatic insufficiency and when additional palpable masses were noted, the snake was euthanatized. Necropsy and histopathologic examination confirmed metastasis of the previously removed adenocarcinoma to the liver, right kidney, and large intestine.

P16INK4a Expression Analysis as an Ancillary Tool for Cytologic Diagnosis of Urothelial Carcinoma

We immunochemically studied p16(INK4a) expression in 116 urine cytologic samples and compared results with 190 histologic samples. The cytologic samples were classified into 4 groups: 1, mild cellular atypia; 2, moderate cellular atypia; 3, severe cellular atypia; and 4, malignancy. Overexpression of p16(INK4a) was detected in none of 32 cases in group 1, 8 (16%) of 50 cases in group 2, 5 (42%) of 12 cases in group 3, and 11 (50%) of 22 cases in group 4. In addition, by histologic analysis, p16(INK4a) overexpression was not detected in nonneoplastic urothelium, except for a few cases of reactive atypia, but it was detected in about 50% of urothelial carcinomas. In particular, a high incidence (16/20 [80%]) of p16(INK4a) overexpression in high-grade carcinomas was noted in cytologic samples. Immunocytologic analysis of p16(INK4a) expression in cytologic samples is a useful ancillary tool for detection of urothelial carcinoma with infiltrating potential.

Salivary Gland Myoepithelioma with Focal Capsular Invasion

Salivary gland tumors that display myoepithelial differentiation exclusively or predominantly are relatively uncommon, and the assessment of malignancy in a myoepithelial tumor can be difficult. We report a case of parotid gland myoepithelioma composed predominantly of spindle cells with focal capsular invasion. The patient was a 65-year-old woman who presented with a painless mass in the right preauricular region. Histologically, the tumor had a solid and multinodular growth pattern and was predominantly made up of spindle cells with a minor component of epithelioid cells with moderate cellular atypia. Focal regions of tumor cells infiltrated the capsule with tongue-like processes, but tumor infiltration into the adjacent parotid tissue was absent. The tumor cells showed strong cytoplasmic immunoexpression of vimentin, pankeratin, S-100 protein, and smooth-muscle actin. Immunostains with glial fibrillary acidic protein, melanoma marker, epithelial membrane antigen, and carcinoembryonic antigen were negative. Expression of p53 was observed focally in the nuclei of the tumor cells. A final diagnosis of salivary gland myoepithelioma with focal capsular invasion was made, and the case was regarded as a myoepithelial tumor of uncertain malignant potential. In this report, we discuss the histologic criteria required to diagnose malignancy in salivary gland myoepithelial tumors.

Metastasizing epithelioid hemangioendothelioma of the nose in childhood

Epithelioid hemangioendothelioma (EHE) arising in the skin is extremely rare, and the majority of documented cases have developed in soft tissues or parenchymatous organs. We report on a 9-year-old boy who presented with a painful erythematous plaque on the nose. Histopathological findings showed a dermal tumor composed of epithelioid cells with moderate cellular atypia and characteristic intracytoplasmic vacuoles. Immunohistochemical stainings confirmed the vascular nature of the tumor. On the basis of these findings, the diagnosis of an EHE was made. Then, two cervical lymph nodes were excised and adjuvant therapy with interferon alpha 2b was initiated. Eighteen months after diagnosis, there is no evidence of local tumor recurrence or metastases. To our knowledge, this is the first report of a metastasizing cutaneous EHE on the nose in childhood. As our case shows, this rare tumor entity has to be considered as a differential diagnosis in neoplasms of the skin, even in childhood.

Leiomyosarcoma of the Sacral Bone in a Patient with a Past History of Resection of Uterine Leiomyoma

We report here a case of leiomyosarcoma in the sacrum with a differential diagnosis of metastasizing leimyoma of uterus, since the patient had a past history of resection of uterine leimyoma 19 years ago. The sacral tumor was an osteolytic lesion, 8x6 cm in size on radiological examination. Microscopically, tumor cells consisted of spindle shaped cells with moderate cellular atypia. The tumor cells invaded into the surrounding muscle tissue. Immunohistochemistry revealed that the tumor cells were positive for α -SMA and vimentin, and they were enclosed by type IV collagen, suggesting the presence of the basement membrane. The labeling index of Ki-67 in the tumor cells was 25%. Re-examination of leiomyomas of uterus resected 19 years ago showed that they were typical leiomyomas, showing well-circumscribed tumors, composed of well-differentiated smooth muscle cells without nuclear atypia. The presence of radiological and pathological findings of malignancy of the sacral tumor excluded the possibility of metastasizing leiomyoma, suggesting that the sacral tumor was another primary tumor.

Clinical, Pathological, and Molecular Studies of Two Families with Iodide Organification Defect.

Two unrelated families (CA and NA) in which an iodide organification defect (lOD) was present in two siblings of each family were studied. These patients had congenital goiters with hypothyroidism and a positive perchlorate discharge test. Examination of the thyroid tissue revealed no thyroid peroxidase (TPO) activity. Histologic findings were consistent with a microfollicular pattern of hyperplasia. Moderate cellular atypia was present, characterized by nuclear pleomorphism and hyperchromatism. Full length thyroglobulin was purified by gel filtration, but was not iodinated. Immunohistochemical studies using a polyclonal anti-human thyroid peroxidase (hTPO) antibody confirmed the presence of immunoreactive TPO protein in the thyroid tissues. Samples of normal and affected individuals were studied with respect to the presence of various fragments using TPO probes of varying sizes. The two affected siblings from family CA were homozygous for fragments 3.9, 4.6, and 7.0 kb (8g111) and 2.3 and 2.9 kb (Ta ql), whereas the parents were heterozygous. In the other family (NA), the Bg/ll digestion and TPO-31 hybridization revealed an interesting and informative polymorphism. The parents showed two different polymorphic patterns: the father had a 5.0/4.6 kb pattern and the mother a 4.7/4.5 kb pattern. However, the two affected siblings showed the same heterozygotic allelic pattern at 4.5/4.6 kb. The restriction fragment length polymorphism detected in these two families suggests an association between the TPO gene and an lOD. Results suggest that in these dyshormonogenetic tissues an altered TPO protein molecule is being synthesized, without detectable in vitro activity, but visible by immunostaining techniques in the goitrous tissue. Mutations in the TPC gene sequence are most likely associated with these changes.

Deoxyribonucleic acid flow cytometry of testicular Leydig cell tumors

We analyzed by flow cytometry the deoxyribonucleic acid content of 13 paraffin embedded, formalin-fixed Leydig cell tumors of the testis. Of the tumors 10 were clinically benign (9 diploid and 1 aneuploid) and 3 were malignant (aneuploid). The benign aneuploid tumor showed moderate cellular atypia and a low mitotic count (less than 2 per 10 high power fields). Our study suggests that the majority of Leydig cell tumors are diploid and the less common malignant tumors are typically aneuploid, and that deoxyribonucleic acid flow cytometric findings can be useful as a prognostic indicator in these tumors.

Uterine Smooth-Muscle Tumors of Uncertain Malignant Potential

To determine whether tumors meeting the criteria of Hendrickson and Kempson for uterine smooth-muscle tumors of uncertain malignant potential have a natural history different from those of leiomyomas and leiomyosarcomas. Tumors with five to ten mitoses per ten high-power fields and with mild or moderate cellular atypia were classified as tumors of uncertain malignant potential. Tumors with two to four mitoses per ten high-power fields and severe cellular atypia would also be classified as tumors of uncertain malignant potential, but we had no tumors that fell into this latter group. Forty-seven women with leiomyosarcoma or smooth-muscle tumors of uncertain malignant potential were identified. Paraffin-embedded blocks were recut, and hematoxylin and eosin-stained sections were studied for mitotic counts and cellular atypia. Statistical analysis used chi 2, Fisher exact test, Student t test, and Kaplan-Meier life table analysis. Fifteen tumors were classified as uncertain malignant potential and 32 as leiomyosarcomas. The patients with leiomyosarcoma were significantly older and more likely to present with extrauterine disease. Those with tumors of uncertain malignant potential had a 5-year disease-free survival of 66% and overall survival of 92%, compared to 28 and 40%, respectively, for leiomyosarcomas; these differences were statistically significant. Patients with tumors of uncertain malignant potential tended to have a protracted clinical course after development of recurrence, and several survived longer than 5 years with metastatic disease. Patients with five to ten mitoses per ten high-power fields and mild to moderate cellular atypia had a prognosis significantly better than that of patients with leiomyosarcomas. In this group, only 27% developed a recurrence, and after recurrence they tended to have a protracted course. Some of these tumors do have a very aggressive course, and the term "uncertain malignant potential" is appropriate.

Hematoporphyrin derivative in the detection and localization of radiographically occult lung cancer.

Hematoporphyrin derivative used in conjunction with the Mayo Clinic bronchofiberscopic fluorescence detection system allows accurate localization of radiographically occult early squamous cell carcinoma. Thirteen tumors were localized in 10 patients with radiographically occult lung cancer. Six were in situ with or without microinvasion and were also bronchoscopically occult. Localization of these 6 tumors was expedited by the use of hematoporphyrin derivative and the bronchoscopic fluorescence detection system. Hematoporphyrin-derivative fluorescence was not specific for carcinoma and was also detected in areas of moderate and marked squamous cellular atypia. Thus, although detection of hematoporphyrin-derivative fluorescence suggests the presence of cancer, proof depends on histologic or cytologic confirmation.

Transitional cell epithelioma of the bladder: correlation of cytologic and histologic diagnosis.

The cytologic and histologic diagnoses have been compared in 83 non-treated bladder tumours and 26 recurrent tumours after surgical treatment, involving a total of 99 patients. A histologic grading into five groups, based on the cellular characteristics of the tumour, has been used. A further 96 cases with no tumour of the urinary tract have been examined cytologically. Generally speaking the conformity is good. It should be possible to reduce the number of unsatisfactory smears and of indecisive cytologic diagnoses through increased experience and improved techniques. The cytologic diagnosis is useful in the prognostic evaluation of individual cases, particularly respecting tumours with histologically moderate cellular atypia (grade II), which appear to constitute a biologically heterogenous group.The material does not yet permit an appraisal of the accuracy of cytology in the follow-up after radiation treatment. It is quite evident, however, that a recurrence can be detected cytologically long before it...