Marked Cellular Atypia Research Articles

Cachexia secondary to intracranial anaplastic (malignant) ependymoma in a boxer dog

An eight-year-old female boxer was referred because of weight loss of several months' duration. On physical examination, cachexia was the only reported abnormality. Neurological symptoms were shown only in the last days preceding death and consisted of altered mental status, compulsive behaviour and left rear proprioception deficit. At post-mortem examination, a voluminous, soft, haemorrhagic mass was found invading the floor of the brain. Based on the morphological features of the tumour, marked parenchymal invasion, extensive necrosis and cellular atypia, the mass was classified as an anaplastic ependymoma. This case report shows similarities to the diencephalic syndrome reported in human paediatric medicine in which the main clinical sign is a profound emaciation in spite of normal or slightly diminished caloric intake. Weight loss and cachexia are clinically relevant problems in small animals and these clinical signs should raise a suspicion, among the other differentials, of a brain tumour, even in absence of neurologic signs.

Primary Pulmonary Choriocarcinoma Presenting with a Hemothorax

Primary pulmonary choriocarcinoma is an extremely rare condition that is difficult to diagnose. In this report, we describe a case of primary pulmonary choriocarcinoma that presented with a hemothorax, initially diagnosed as an ectopic pregnancy. The patient was treated successfully with surgery followed by combination chemotherapy. In rare instances such as this, choriocarcinoma can originate in sites outside the genital tract; a thorough and thoughtful evaluation will ensure an accurate diagnosis and prompt treatment.

Apocrine hidradenocarcinoma showing Paget’s disease and mucinous metaplasia

A 54-year-old man presented with a solitary, erythematous, rapidly growing 1-cm nodule on his scalp that had arisen over the previous 3 months. He had no history of skin cancer. An excisional biopsy of the lesion showed a fairly well-circumscribed but focally invasive tumor consisting of areas of typical-appearing clear cell hidradenoma as well as areas with mucinous goblet-type cells and cells with eosinophilic cytoplasm and decapitation-type secretion. There was marked cellular atypia, numerous atypical mitotic figures and focal necrosis. The tumor cells focally involved the overlying epidermis (Paget's disease). Large areas of mucin were identified throughout the lesion. The tumor cells stained with markers for cytokeratin 7 and focally for EMA and CEA, confirming ductal differentiation. The goblet cells and mucinous areas stained with mucicarmine and PASD. The patient was diagnosed with hidradenocarcinoma with mucinous differentiation. Associated Paget's disease has only rarely been reported, and mucinous metaplasia is a previously unreported feature in hidradenocarcinoma.

Spindle cell oncocytoma of the adenohypophysis: report of a case with marked cellular atypia and recurrence despite adjuvant treatment

Spindle cell oncocytoma (SCO) of the adenohypophysis is a recently defined pituitary tumor mimicking a non-functioning macroadenoma and composed of mitochondrion rich tumor cells, positive for S-100, vimentin, epithelial membrane antigen and galectin-3 but lacking cytokeratins, pituitary hormones, and neuroendocrine markers. Derivation from pituitary folliculostellate cells (FSCs) has been suggested based upon immunohistochemical and ultrastructural characteristics shared by SCO and FSCs. 10 cases of SCO have been reported to date; of these, 8 underwent a benign clinical course and 2 recurred. We report a case of SCO with typical histologic and immunohistochemical features in addition to marked cellular pleomorphism and nuclear atypia. It showed slow regrowth over a 30-month period of follow-up despite combined surgical and radiotherapy. Despite the benign course of most reported cases, additional experience with longer follow-up are needed to assess clinical, histopathologic, and proliferative indices and their relevance to optimal therapy for this rare pituitary tumor.

A Case of Spontaneous Malignant Hibernoma in a Crl:CD(SD)IGS Rat

A firm, tan, well-circumscribed mass that measured 25 × 30 × 35 mm was observed in the thoracic cavity of a 53-week-old male Crl:CD(SD) IGS rat. Histologically, the mass was encapsulated by fibrous tissue and contained fibrovascular septae. Tumor cells were compactly arranged, and most were oval to polygonal in shape with multivacuolated cytoplasm and a centrally located nucleus. In some parts of the tumor, marked cellular atypia and frequent mitoses were evident. Vacuoles in cytoplasm were positive for oil red O. The tumor cells were characterized ultrastructurally by abundant, round to oval mitochondria with transverse closely-packed cristae. Tumor cells were immunohistochemically positive for uncoupling protein 1 (UCP-1). Several thrombi and hemorrhagic or necrotic foci were also observed within the tumor mass. Vascular invasion of the tumor capsule was observed; however, invasion of surrounding tissues or metastases were not observed. Based on the pathology findings, this case was diagnosed as a malignant hibernoma.

Fine needle aspiration cytology of myxoid lesions of soft tissues: a study of 24 cases

To summarize the diagnostic features of fine needle aspiration cytology (FNAC) of myxoid lesions in soft tissue, and to define the cytological criteria for differentiating benign lesions from sarcomas and between various myxoid lesions. FNAC data of 24 soft tissue myxoid lesions (14 benign lesions, 10 malignant lesions) from 1993 to 2006 from Kiang Wu Hospital, Macau were reviewed in correlation with the clinical course or the results of biopsy. Ganglion, myxoma, and myxoid nodular fasciitis were the most common benign myxoid lesions of the soft tissues, all of which had low cellularity and lack of marked cellular atypia in smears in common. Ganglion was characterized by the disappearance of or the gradual minimization of the nodule after aspiration and the lack of blood vessel in smears. Myxoid nodular fasciitis was characterized by a pleomorphic pattern of proliferative cells and the presence of ganglion cell-like cells. Myxoid liposarcoma, extraskeletal myxoid chondrosarcoma and myxofibrosarcoma were the most common myxoid sarcomas. Cytologically, they had high cellularity and various degrees of cellular atypia. Myxoid liposarcoma exhibited branching chicken-wire like capillary vessels and/or lipoblasts; myxofibrosarcoma were prominent in both pleomorphic and atypia of the cells. The data revealed that the diagnostic accuracy of FNAC was nearly 100% in differentiating benign and malignant myxoid lesions of the soft tissues. The coordinate rate to the histopathology diagnosis of the common myxoid lesions of the soft tissues was above 75% (benign 71.4% and malignancy 80% respectively). FNAC is an effective method in diagnosing myxoid lesions of soft tissue, in correlation with the clinical data and the accessory examinations. FNAC can provide an objective basis for the treatment of myxoid lesions and prevention of unnecessary surgical operations.

Carcinoma in a Mixed Mammary Tumor in a Llama (Lama Glama)

A 13-year-old female llama was presented to the referring veterinarian for swelling and firmness of the right rear mammary gland, for a duration of 2 months, which had been unresponsive to antibiotics. A formalin-fixed wedge biopsy specimen from the affected quarter was submitted to Purdue University Animal Disease Diagnostic Laboratory for histopathology. Histopathologic examination revealed tubulopapillary acinar or solid nest-like clusters of neoplastic epithelial cells surrounded by whorls and sheets of proliferative myoepithelial cells. Histologic criteria for malignancy observed in neoplastic epithelial cells included marked cellular and nuclear atypia, high mitotic index, and numerous bizarre mitoses. The presence of osseous metaplasia in the proliferative mesenchymal component justified classification as a mixed tumor. Positive immunohistochemical staining of neoplastic epithelial cells with anticytokeratin antibody, and proliferative spindloid cells with antiviemtin and antismooth muscle actin antibodies supported the histopathologic diagnosis. The llama was in good health after about 1 year of initial presentation, and metastasis to regional lymph nodes was not reported. Mammary neoplasia is rare in camelids. To the authors' knowledge, this is the first report of a carcinoma in a mixed mammary tumor in a llama.

Multicentric epithelioid angiosarcoma of the spine: a case report of a rare bone tumor

Background context Epithelioid angiosarcoma (EA) is a high-grade sarcoma of vascular origin. EA is a rare variant of angiosarcoma. It is characterized by large cells with an epethelioid morphology. EA has been reported in sites like skin thyroid, adrenal gland, soft tissue, and rarely in bone. Purpose The current article describes a case of multicentric EA of the spine that presented simultaneously at T4 spine and the posterior one third of the left fourth rib. Study design/settings This study included a patient with a rare spinal tumor, which presented insidiously. Radiologically, the lesions were osteolytic with erosion of cortices. The tumor was composed of nests and cords of malignant cells with epithelioid morphology with areas of vascular differentiation, necrosis, and hemorrhage. Anastomosing vascular spaces lined by epithelioid endothelial cells suggested focal endotheliod differentiation. Methods Histopathological evaluation of the tumor obtained from en bloc resection of the fourth rib and specimen from decompression of the fourth thoracic vertebra was done. Immunohistochemistry showed positivity for endothelioid cell markers like CD31 and factor VIII related antigen. The authors point out the need for immunohistochemical evaluation after careful histological analysis for vascular differentiation for an accurate diagnosis of vascular bone tumors with epithelioid features so that an erroneous diagnosis of metastatic carcinoma can be avoided. EA occurs rarely in bone. EA is marked by the presence of large polygonal epithelioid malignant cells with marked cellular atypia and pleomorphism. The arrangement of the cells may mimic epithelial neoplasm. These types of lesions are a definite diagnostic challenge in bone biopsy. The tumor was treated with en bloc resection of the rib and decompression of the body of T4 spine, followed by megavoltage radiotherapy. Follow-up X-rays showed regression of the tumor at 2 years. CD31 is the most sensitive marker for EA. Even in the absence of obvious vascular differentiation, abundant intratumoral hemorrhage and intratumoral neutrophils are definite morphologic changes that should suggest a vascular origin. Results The patient was followed up for 2 years. A conservative surgical approach with a radical course of megavoltage radiotherapy could yield a good result in EA of bone. At the time of writing this report, there is no evidence of tumor recurrence. Conclusion It is important to differentiate EA from other tumors because the clinical course and treatment are specific for these conditions. Careful histologic and immunohistochemical analysis will clinch the diagnosis. Even though rare, we stress the importance to be aware of the existence of this tumor, which is essential for correct diagnosis.

Sustentaculoma

A case of a morphologically distinctive tumor of the adrenal medulla occurring in a 54-year-old woman is described. On microscopic examination, the tumor was well circumscribed and characterized by the presence of ill-defined, irregular nests of spindle cells with oval to elongated nuclei, tiny nucleoli, and abundant eosinophilic cytoplasm. The tumor was associated with a moderate infiltrate of lymphocytes and plasma cells with occasional lymphoid follicles. Necrosis, marked cellular atypia, and mitoses were absent. Immunohistochemical studies demonstrated the tumor cells to be strongly reactive for vimentin, S-100 protein, and CD56, and nonreactive for glial fibrillary acidic protein, chromogranin, synaptophysin, melanoma-associated antigens, and dendritic cell markers. Ultrastructural examination showed elongated cells with interdigitating cytoplasmic processes devoid of a basal lamina. No secretory granules were noted. The morphology, immunophenotype, and ultrastructure of this unique neoplasm suggest derivation from sustentacular cells of the adrenal medulla. We propose the designation "sustentaculoma" for this hitherto undescribed neoplasm of the adrenal gland.

Malignant Proliferating Trichilemmal Tumor of the Lower Eyelid

To report on the first case of malignant proliferating trichilemmal tumor (PTT) on the eyelid, and to describe the clinical and histopathologic findings. Interventional case report and literature review. A 42-year-old woman presented with a 2-year history of a firm, 3 x 2 cm lower eyelid mass. The mass was excised with the frozen section control. The defect in the lower eyelid was reconstructed with modified Hughes tarsoconjunctival flap and skin graft from the left postauricular area. Histopathologic examination revealed the proliferation of outer hair sheath epithelium with multiple central areas of trichilemmal keratinization. The presence of marked cellular atypia and frequent mitoses indicated the malignant transformation. Malignant PTT has not yet been reported on the eyelid. Malignant PTT should be included in the differential diagnosis for eyelid tumors.

Microscopic In Vivo Description of Cellular Architecture of Dermoscopic Pigment Network in Nevi and Melanomas

To characterize the microscopic aspects of the dermoscopic pigment network in vivo, by means of confocal scanning laser microscopy. Confocal imaging was performed on melanocytic lesions characterized by pigment network at dermoscopy. Some confocal architectural and cytologic features, as observed at the dermoepidermal junction, were morphologically described and quantified by means of a dedicated program. University medical department. We studied confocal images of 15 melanomas, 15 dermoscopic atypical nevi, and 15 common nevi. Features referring to aspect, size, regularity, homogeneity, and infiltration of dermal papillae and to cellular size, regularity, and atypia were described by 2 observers on confocal images. Mean dermal papillary diameter, mean cell area, and shape irregularity were quantified by drawing papillae and cell contours on confocal images and measured with the use of a computer program. Pigment network in melanomas consisted of large basal cells that circumscribed small to medium-sized dermal papillae with marked cellular atypia, sometimes infiltrating dermal papillae. On the other hand, common acquired nevi were characterized by lack of atypical cells and edged dermal papillae. Atypical nevi presented intermediate characteristics between clearly benign and malignant lesions. Cellular atypia was the most sensitive feature for melanoma diagnosis, whereas the presence of nucleated cells infiltrating dermal papillae was the most specific one.

Forearm Mass in an Adolescent

Forearm Mass in an Adolescent

Cellular angiofibroma and related fibromatous lesions of the vulva: report of a series of cases with a morphological spectrum wider than previously described

Cellular angiofibroma (CA) is a rare benign mesenchymal lesion with a predilection for the vulval region. In this report we aim to describe the clinical, pathological and immunohistochemical features of a series of vulval mesenchymal lesions, some of which have the classically described histological appearance of CA while others exhibit atypical features. We believe these lesions fall within the broad spectrum of fibromatous lesions of the vulva. Seven cases were included. Histological sections were examined and immunohistochemical staining with vimentin, desmin, alpha smooth muscle actin, h-caldesmon, S100, EMA, AE1/3, CD34, CD10, ER, PR and MIB1 was performed. The patients' ages ranged from 20 to 65 years and the lesions ranged in size from 10 to 50 mm. All lesions were well circumscribed, moderately cellular lesions and were composed of bland spindle-shaped cells set in a fibrous stroma. Many blood vessels with thick hyalinized walls were present in four cases, in one case occasional such blood vessels were present and in two cases vessels with thick hyalinized walls were not present. In five cases the vessels were at least focally dilated resulting in a haemangiopericytomatous pattern. Histological features identified in a variable numbers of cases included peripheral adipose tissue (four cases), adipose tissue within the centre of the lesion (one case), stromal mast cells (six cases), stromal lymphoid aggregates (five cases), scattered multinucleate cells (five cases), hypocellular hyalinized areas (two cases), myxoid areas (four cases) and focal areas of marked cellular atypia reminiscent of symplastic change within a uterine leiomyoma (one case). Mitotic figures were identified in four cases, all with a mitotic count of < 1 per 10 high-power fields. Immunohistochemically all neoplasms were positive with vimentin and all but one with ER and PR (PR staining was not performed in one tumour). In all cases desmin, alpha smooth muscle actin, h-caldesmon, S100 and AE1/3 were negative (h-caldesmon and AE1/3 staining were not performed in one case). Three cases were positive with CD34, one with EMA and two with CD10. All exhibited a low MIB1 proliferation index of approximately 1%. One lesion recurred locally 6 months following initial removal. CA is a rare benign vulval mesenchymal lesion with limited potential for local recurrence. We describe several hitherto unreported histological features which add to the morphological spectrum. Although not all lesions exhibit the classically described histological features of CA, we believe all fall within the broad spectrum of benign vulval fibromatous lesions. These cases are characterized by vimentin positivity but negative staining with smooth muscle markers which assists in excluding many of the other vulvovaginal mesenchymal lesions which enter into the differential diagnosis. The immunophenotype indicates that CA probably exhibits fibroblastic rather than myofibroblastic differentiation. These lesions are almost always positive with ER and PR, suggesting that they probably arise from the hormone receptor-positive subepithelial mesenchymal layer within the lower female genital tract.

Toxicodermia por metotrexato con marcada dismaduración epidérmica

Abstract—Methotrexate is a competitive folic acid inhibitor and interferes with DNA synthesis. Skin reactions from methotrexate are infrequent and highly varied, and may or may not be a sign of toxicity. We present two patients treated with 35 mg. a week of methotrexate, one for psoriasis and the other for rheumatoid arthritis, who developed mucous and skin lesions related to this drug. The patient with psoriasis also presented with erosion and bleeding of the psoriasis plaques and hepatic and hematologic toxicity. The histological changes suggested a cytotoxic effect from chemotherapy, and presented with a discrete vacuolar interface dermatitis with marked epidermal dysmaturation, cellular atypia and eccrine squamous syringometaplasia. In both patients, we interpreted the mucocutaneous lesions as a sign of toxicity from the drug.

Gynecomastia With Marked Cellular Atypia Associated With Chemotherapy A Diagnostic Pitfall in Fine-Needle Aspiration

c Gynecomastia is a common benign male breast disease, which may exhibit mild cellular atypia in cytology specimens. However, marked cytologic atypia can be seen in gynecomastia superimposed by chemotherapy. The case described in this report demonstrated severe cytologic atypia of gynecomastia mimicking carcinoma in a patient treated with chemotherapy for acute leukemia. A distinct cytologic feature helpful in avoiding the diagnostic error is described, namely, atypical cells admixed with bland ductal cells and appearing at a different plane. The importance of applying strict diagnostic criteria in breast cytology and clinical correlation is also emphasized. (Arch Pathol Lab Med. 2002;126:613‐614)

Prostate Duct (Endometrioid) Adenocarcinoma Simulating Urothelial Carcinoma

Prostate duct adenocarcinoma, previously referred to as endometrioid carcinoma because of its histological resemblance to endometrial carcinoma, is a rare prostatic malignancy. Histologically, this tumor is characterized by marked cellular atypia and pleomorphism. The main differential diagnosis includes high-grade prostatic intraepithelial neoplasia and urothelial carcinoma. We present a case of 78 yr old male with a prostate duct adenocarcinoma simulating urothelial carcinoma. Immunohistochemical studies were crucial to establish the diagnosis. (The J Histotechnol 24:121, 2001)Submitted: February 19, 2001; Accepted with revisions: February 20, 2001

Prostate Duct (Endometrioid) Adenocarcinoma Simulating Urothelial Carcinoma

Prostate duct adenocarcinoma, previously referred to as endometrioid carcinoma because of its histological resemblance to endometrial carcinoma, is a rare prostatic malignancy. Histologically, this tumor is characterized by marked cellular atypia and pleomorphism. The main differential diagnosis includes high-grade prostatic intraepithelial neoplasia and urothelial carcinoma. We present a case of 78 yr old male with a prostate duct adenocarcinoma simulating urothelial carcinoma. Immunohistochemical studies were crucial to establish the diagnosis. (The J Histotechnol 24:121, 2001)Submitted: February 19, 2001; Accepted with revisions: February 20, 2001

Carcinomas in situ of the breast with indeterminate features: role of E-cadherin staining in categorization.

Most breast carcinomas in situ (CIS) are easily categorized as ductal (DCIS) or lobular (LCIS). However, some CIS have indeterminate histologic features (CIS-IF). Prior studies have shown that E-cadherin protein expression is lost in lobular but not ductal carcinomas. Therefore, evaluation of examples of CIS-IF for E-cadherin expression by immunohistochemistry might be useful in helping to define their nature. To address this, we studied histologic features and E-cadherin expression by immunohistochemistry in 89 cases of breast CIS (28 LCIS, 33 DCIS, 28 CIS-IF). CIS-IF cases were divided into three groups based on histology: Group 1 cases had all the cytologic and architectural features typical of LCIS but showed areas of comedo-type necrosis (n = 6). Group 2 cases were CIS lesions characterized by small, uniform neoplastic cells either growing in a solid pattern with focal microacinar-like structures but with cellular dyshesion, or growing in a cohesive mosaic pattern but with occasional intracytoplasmic vacuoles (n = 17). Group 3 cases showed marked cellular pleomorphism and nuclear atypia but had the dyshesive growth pattern characteristic of LCIS (n = 5). E-cadherin staining was scored as negative, positive, or mixed (mixture of negative and positive tumor cells). All 28 cases of LCIS were E-cadherin negative, and all 33 DCIS cases were E-cadherin positive by immunohistochemistry. All cases from CIS-IF group 1 and group 3 were negative for E-cadherin, suggesting a closer kinship to LCIS than to DCIS. In contrast, CIS-IF group 2 cases were heterogeneous with respect to E-cadherin staining. Six (35.3%) cases were E-cadherin negative (more akin to LCIS), 5 (29.4%) cases were E-cadherin positive (akin to DCIS), and 6 (35.3%) cases had both E-cadherin-positive and E-cadherin-negative tumor cells, suggesting a mixed DCIS/LCIS phenotype. Our findings suggest that E-cadherin immunostaining is of value in helping to characterize breast carcinomas in situ with indeterminate features. However, validation of these observations will require clinical outcome studies.

Unique Cellular Features in Atypical Adenomatous Hyperplasia of the Lung: Ultrastructural Evidence of Its Cytodifferentiation

Atypical adenomatous hyperplasia (AAH) of the lung could be a good material to understand the histogenesis of peripherally occurring, well-differentiated adenocarcinoma. However, its true biological significance remains to be clarified. The authors present the histomorphological studies of this lesion and compare the ultrastructure with that of nonmucinous bronchioloalveolar carcinoma (BAC) to define characteristic features of AAH. Light microscopy showed the well-preserved pulmonary architecture, proliferated neoplastic cells without marked cellular atypia, and no transitional area to obvious adenocarcinoma. Intranuclear inclusion was present in a large number of neoplastic cells. Electron microscopy revealed that cuboidal or low columnar neoplastic cells proliferated actively but were not crowded on slightly thickened fibrous alveolar septa with both Clara-like granules and small lamellar bodies in the cytoplasm resembling that of Clara cell and type 2 pneumocyte. Some of the nuclei had characteristic invaginations of its nuclear membrane. Although the findings appear to be nonspecific for AAH, the authors emphasize that AAH is an alveolar intraepithelial neoplasia that represents a very early stage in the continuous developmental spectrum of adenomatous neoplasia in the bronchioloalveolar region corresponding to dysplasia or intraepithelial neoplasia in other organs, and will give the significance to speculate its histogenesis.

Neuroendocrine carcinomas (carcinoid tumor) of the thymus. A clinicopathologic analysis of 80 cases.

We studied 80 cases of primary thymic neuroendocrine carcinomas. Most patients had symptoms; approximately one third were asymptomatic. All cases were treated by surgical excision. The tumors were divided according to histopathologic features into low- (n = 29), intermediate- (n = 36), and high-grade (n = 15) types. The tumors displayed a variegated histologic appearance and unusual cytologic features. Some cases showed transition from low to high grade within the same tumor mass. Mitotic activity ranged from fewer than 3 to more than 10 mitotic figures per 10 high-power fields, and most tumors displayed marked cellular atypia and areas of necrosis. In 73 patients, the tumor was confined to the anterior mediastinum. Positive immunohistochemical reaction was observed using antibodies for CAM 5.2 low-molecular-weight cytokeratins, broad-spectrum keratin, chromogranin, synaptophysin, and Leu-7. The clinical follow-up obtained in 50 patients correlated well with tumor differentiation. Therefore, the behavior of these tumors seems to correlate with histologic grade, which seems directly proportional to degree of differentiation. We propose replacing the term thymic carcinoid with thymic neuroendocrine carcinoma, which better reflects the aggressive biologic behavior of these tumors in the mediastinal location.