Noncohesive Cells Research Articles

Overdiagnosis of lobular carcinoma of breast- A review of histomorphological features and immunohistochemistry: A case series

: Invasive lobular carcinoma (ILC) accounts for 5%–15% of all invasive breast cancers (BCs) and is the second most common type of BC behind invasive ductal carcinoma (IDC) of no special type. ILC of the breast is characterized morphologically by small, noncohesive cells that infiltrate the stroma in a single-file pattern(Indian file pattern). ILC tumours display features associated with a good prognosis, being low grade, oestrogen receptor positive and is mainly associated with the complete loss of E-cadherin (E-cad) expression.To review the cases of invasive lobular carcinoma and to immunohistochemically categorize IDC and ILC.This is a retrospective study including all the modified radical mastectomy cases of invasive lobular carcinoma of breast reported in the department of Pathology of a tertiary care centre from January 2021 to January 2022. Histopathological and immunohistochemical analysis of those cases were reviewed.We encountered 10 cases of invasive lobular carcinoma of breast from January 2021 to January 2022. The average age of the patients was 55.9 years old (35–72). The classic presentation was a breast lump found in 100% of the cases. On physical examination, breast carcinoma was suspected in all the patients. The average size of the tumours was 4.5 cm (1.4– 9cm). Out of those 10 cases, 4 cases were right sided lesion and modified radical mastectomy was performed in all the 10 cases. All the 10 cases were diagnosed as invasive lobular carcinoma on histopathology and review of those cases showed 7 out of 10 cases to be IDC. Those cases showed pitfalls in histomorphological analysis which were later confirmed by immunohistochemistry. The findings are presented in the study.Our study found that there was a histomorphological pitfall in the diagnosis of IDC. In ambiguous cases with histologically equivocal features, a strong, complete, membranous E-cadherin expression may help in resolving the problem and in aiding in the subclassification of invasive breast carcinoma.

Diffuse Large B-cell Lymphoma of the Prostate: Case Study of an Uncommonly Encountered Entity

Abstract Introduction/Objective Hematologic neoplasms comprise less than 1% of prostate malignancies, with diffuse large b-cell lymphoma (DLBCL) accounting for 15% of those. Chronic lymphocytic leukemia/small lymphocytic lymphoma is most often seen, comprising 53% of lymphomas at this site, with the remainder consisting of marginal zone, mantle cell, and follicular lymphomas. Methods/Case Report Our case involves a 51-year-old African American male presenting to a medium-sized academic medical center with a chief complaint of hematuria with clot retention. Patient did endorse night sweats and chills at this time. Imaging revealed an 11 cm mass involving the prostate and bladder, a 10 cm right adrenal mass, and pelvic lymphadenopathy. A cystoscopy with transurethral resection was performed with tissue histology showing complete effacement of prostatic parenchyma by sheets of medium-sized, mildly irregular, non-cohesive cells with minimal cytoplasm. Tissue morphology appeared highly suspicious for lymphoma, but the rarity of this process along with the possibility of other lesions led to differential diagnoses including small cell carcinoma, poorly differentiated prostatic adenocarcinoma, high-grade urothelial carcinoma, and granulomatous prostatitis. Immunohistochemical staining of neoplastic cells showed CD20+ B cells with a non-germinal center immunophenotype (CD10-) and co-expression of Bcl-2 and c-myc. Subsequent FISH analysis demonstrated a Bcl-6 gene rearrangement without a Bcl-2 or MYC rearrangement. Ki67 was positive in 90% of tumor cells. Rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone was initiated for stage IV DLBCL with prophylactic intrathecal methotrexate. The patient has received 6 cycles of chemotherapy to date with resolution of the prostate and adrenal masses. Bladder involvement is still seen radiographically, but is suspected to be mainly necrotic tissue. Results (if a Case Study enter NA) N/A Conclusion Less aggressive lymphomas are more common, which makes this presentation additionally unexpected. We employed a wide battery of immunohistochemical stains, including NKX3.1, s100, gata-3, pan-ck, CD68, and chromogranin and synaptophysin, when initially evaluating the neoplastic tissue.

Clinicopathologic Study of Gleason Pattern 5 Prostatic Adenocarcinoma With "Single-cell" Growth Reveals 2 Distinct Types, One With "Plasmacytoid" Features.

Each Gleason score category of prostatic adenocarcinoma (or Grade Group) may encompass a diverse group of architectural patterns such as well-formed glands, poorly formed glands, cribriform structures, single cells, and/or solid sheets. We have noted heterogeneity within the single-cell subtype of Gleason pattern 5 prostatic adenocarcinoma that has not been fully addressed. Therefore, we retrospectively reviewed a series of radical prostatectomies with high-grade prostatic adenocarcinoma (Grade Group 4 or 5), identifying tumors with a component of single-cell infiltration. Additional cases identified prospectively were also included. TNM status, association with other histologic patterns, and clinical follow-up status were determined. Immunohistochemistry for NKX3.1, E-cadherin, p120 catenin, and prostate-specific antigen (PSA) were performed in each case. Eighteen cases with a component of well-developed Gleason pattern 5 characterized by single infiltrative cells that comprised ≥5% of the tumor were identified (15/202 retrospective radical prostatectomies with the high-grade disease [7.5%]). The single-cell pattern ranged from 5% to 50% of the tumor volume, with 5 cases containing ≥40%, and variable secondary architecture included diffuse infiltrating single cells with targetoid growth pattern around benign glands, solid expansive nests of noncohesive cells, and corded/single file growth pattern. Further morphologic analysis demonstrated 2 distinct histologic subtypes: (1) (subtype 1; n=9) monomorphic "plasmacytoid" tumor cells with eccentrically placed nuclei and variable intracytoplasmic vacuoles with bland cytology and discohesion and (2) (subtype 2; n=9) more cohesive tumor cells with greater cytologic atypia characterized by prominent nucleoli, greater variability in nuclear size/shape, occasional mitotic figures, and more irregular infiltration. By immunohistochemistry, NKX3.1 nuclear expression and PSA cytoplasmic expression was retained in all cases. Concomitant membranous E-cadherin loss and strong cytoplasmic p120 catenin expression were present in 5 of the 18 (28%) cases, all in subtype 1 (5/9, 56%). Overall, 56% (10/18) of patients had advanced-stage disease (≥pT3b), and 70% (7/10) of these patients had associated lymphovascular invasion. All patients had concomitant cribriform patterns of carcinoma. The outcome was available for 14 patients: 4 died of unknown cause; 6 had biochemical recurrence with distant bone metastasis in 5 of the 6; and 4 patients with <3 years of follow-up currently have undetectable serum PSA levels (2 patients received salvage radiotherapy with androgen deprivation and 2 remain on routine follow-up). In summary, the single-cell pattern of Gleason pattern 5 prostatic adenocarcinoma is uniformly associated with other high-risk histologic patterns (eg, cribriform growth), and high-stage disease with distant metastasis is not uncommon. Our data suggest that the "single-cell" Gleason pattern 5 prostatic adenocarcinoma contains 2 distinct subtypes. Somatic CDH1 alterations may play a role in the development of the "plasmacytoid" pattern characterized by monomorphic cytology with concomitant E-cadherin loss and aberrant p120 catenin expression.

Non-invasive lobular neoplasia of the breast: Morphologic features, clinical presentation, and management dilemmas.

The designation of noninvasive lobular neoplasia applies to atypical epithelial proliferations composed of noncohesive cells secondary to loss or functional alteration of E-cadherin-mediated cell adhesion. The morphologic spectrum of noninvasive lobular neoplasia encompasses atypical lobular hyperplasia (ALH) and classic lobular carcinoma in situ (classic LCIS) and two LCIS variants, namely florid LCIS (F-LCIS) and pleomorphic LCIS (P-LCIS), as defined in the World Health Organization (WHO) Classification of Tumors of the Breast 5th ed. Herein, we review the morphologic, immunohistochemical, and molecular features of noninvasive lobular neoplasia, with special emphasis on F-LCIS and P-LCIS. We also review imaging features, management at core needle biopsy, upgrade rates at surgical excision, and clinical management dilemmas.

The effect of matrix metalloproteinases and adhesion molecules on the prognosis in gastric carcinoma

Background: Matrix metalloproteinases (MMPs), adhesion molecules, and receptors are needed in the process of cancer growth. This study aims to investigate the role of MMP-3, MMP-10, MMP-11, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in gastric cancer. Materials and Methods: Fifty-two gastric carcinoma cases who underwent gastrectomy were included in the study. The cases were inspected with regard to the presence/absence of lymph node and distant metastases. The selected paraffin blocks were immunohistochemically stained with MMP 3, MMP 10, MMP 11, ICAM (CD 54), and VCAM (CD 106). Results: Most of the cases (n: 50, 94%) with gastric cancer manifested cytoplasmic staining with MMP-11. MMP-10 expression was found in 45 of 52 (86.5%), MMP-3 staining was determined in 43 (82.6%) of gastric carcinomas. Different areas of differentiation within the tumor showed differences in MMP expression in terms of intensity and extensiveness. ICAM-1 expression was found in 47 of 52 (90.4%) cases and with VCAM-1, 46/52 (88.5%) of gastric cancers manifested positive staining. Its expression was found to be higher in the nonmetastatic group both in intestinal and diffuse types. VCAM-1 was diffusely expressed in gastric cancers. However, we did not determine a significant correlation concerning differentiation and lymph node and distant metastasis. Conclusions: MMP-3, MMP-10, MMP-11, ICAM-1, and VCAM-1 are expressed in gastric cancers and are thought to be involved in tumor development. Levels of expression that decrease in parallel to decreasing differentiation in areas of differentiation within tumor corroborate the idea that they are related to tumor progression. Due to its relationship with metastasis, ICAM-1 expression in noncohesive cells supports the idea that ICAM-1 is a significant factor involved in metastasis development in gastric cancers. Decreased MMP-10 and MMP-11 expression in metastases suggest that these enzymes may also be linked to the metastatic potential of gastric cancers.

Manipulating Living Cells to Construct a 3D Single-Cell Assembly without an Artificial Scaffold.

Artificial scaffolds such as synthetic gels or chemically-modified glass surfaces that have often been used to achieve cell adhesion are xenobiotic and may harm cells. To enhance the value of cell studies in the fields of regenerative medicine and tissue engineering, it is becoming increasingly important to create a cell-friendly technique to promote cell–cell contact. In the present study, we developed a novel method for constructing stable cellular assemblies by using optical tweezers in a solution of a natural hydrophilic polymer, dextran. In this method, a target cell is transferred to another target cell to make cell–cell contact by optical tweezers in a culture medium containing dextran. When originally non-cohesive cells are held in contact with each other for a few minutes under laser trapping, stable cell–cell adhesion is accomplished. This method for creating cellular assemblies in the presence of a natural hydrophilic polymer may serve as a novel next-generation 3D single-cell assembly system with future applications in the growing field of regenerative medicine.

Contact enhancement of locomotion in spreading cell colonies

The dispersal of cells from an initially constrained location is a crucial aspect of many physiological phenomena ranging from morphogenesis to tumour spreading. In such processes, the way cell-cell interactions impact the motion of single cells, and in turn the collective dynamics, remains unclear. Here, the spreading of micro-patterned colonies of non-cohesive cells is fully characterized from the complete set of individual trajectories. It shows that contact interactions, chemically mediated interactions and cell proliferation each dominates the dispersal process on different time scales. From data analysis and simulation of an active particle model, we demonstrate that contact interactions act to speed up the early population spreading by promoting individual cells to a state of higher persistence, which constitutes an as-yet unreported contact enhancement of locomotion. Our findings suggest that the current modeling paradigm of memoryless interacting active particles may need to be extended to account for the possibility of internal states and history-dependent behaviour of motile cells.

How to approach the many faces of endometrioid carcinoma

This article reviews the salient features of variants of endometrioid carcinoma (ECa) that can pose a diagnostic challenge and/or are associated with unique clinicopathological findings. Variants with distinct architectural and cytologic features include the following: (1) ECa with a villoglandular pattern (tumor with finger-like papillae lined by bland cells with a tendency for vascular/lymphatic invasion and lymph node metastasis once this pattern is seen within the myoinvasive component); (2) papillary ECa of intermediate grade (grade 2) (tumor that can be mistaken for serous carcinoma, as it contains papillae showing slightly irregular contours, moderately atypical cells, and it is associated with vascular/lymphatic invasion/lymph node metastasis, but with common association with mucinous metaplasia, MELF (microcystic, elongated, and fragmented) pattern of invasion, and wild p53 expression); (3) ECa with non-villous papillae (tumor containing pseudopapillae within glands with bland-appearing cytology commonly associated with abortive squamous differentiation and otherwise not different from usual ECa); (4) ECa with microglandular-like pattern (tumor that mimics microglandular hyperplasia of the cervix, often lacking the typical appearance of microglandular hyperplasia and showing Ki-67 index >10%, strong CD10 expression, and negative PAX-2, p63, and CD34); and (5) ECa with sex cord-like formations and hyalinization (tumor with interconnected cords and nests of bland epithelioid and spindled cells that merge with a typical component of low-grade ECa, usually associated with squamous differentiation and hyalinization). This tumor should be distinguished from carcinosarcoma and, in contrast to the latter, it shows nuclear β-catenin expression, ER/PR and patchy p16 positivity, tends to present at a low stage, and has a favorable prognosis and (6) dedifferentiated ECa (tumor showing a low-grade ECa juxtaposed to an undifferentiated carcinoma—the latter characterized by variably sized monotonous, often non-cohesive cells with brisk mitotic activity and usually arranged in sheets). Undifferentiated carcinoma tends to be negative for PAX8 and ER/PR with variable expression of keratins and can be associated with microsatellite instability (may be part of Lynch syndrome). Variants with distinct cytological features include the following: (1) ECa with clear cells (tumors with clearing due to ‘clear' (glycogenated) squamous cells, distinct vacuoles, or not otherwise specified. EC with clear cells should be distinguished from clear cell carcinoma by the absence of the variety of architectural patterns, lack of cuboidal/flattened/hobnail cells, and lack of degree of atypia usually detected in clear cell carcinoma. In addition, they are ER/PR positive and Napsin A and p504S negative in contrast to clear cell carcinoma); (2) ECa with spindle cells (tumor with transition from spindle cells to the glandular component of a low-grade ECa. The spindle cells are keratin, ER/PR, and patchy p16 positive and show wild-type p53 expression); (3) ECa with mucinous differentiation (this tumor can be mistaken for a cervical adenocarcinoma, as they have overlapping features. Expression of ER/PR and vimentin in the context of a negative or patchy p16 positivity and the absence of high-risk HPV allows a correct diagnosis).

A small round cell lesion in the neck of an 11-year-old child

Small round cell lesions in the neck of a pediatric patient may involve a lymph node or present as an extra-nodal solid tumor. Various proliferative lymph node lesions include non-specific reactive hyperplasia, infectious mononucleosis, Castleman’s disease, Rosai-Dorfman disease, Langerhans cell histiocytosis and malignant lymphoma. Besides lymphomas, the other pediatric small round cell tumors (SRCT) of the neck can be a group of malignancies that include neuroblastoma, Ewing’s sarcoma, embryonal rhabdomyosarcoma, and metastasis from retinoblastoma and small cell undifferentiated carcinoma. These lesions are characterized both histologically and cytologically by predominantly small round to oval cells. Special morphological features characterizing these lesions are exclusive noncohesive cells and lymphoglandular bodies for non-Hodgkin lymphoma; rosette formation and filamentous background for neuroblastoma; nuclear molding, acinar formation and paranuclear blue inclusion for metastatic small cell undifferentiated carcinoma; glycogen vacuoles for Ewing’s sarcoma; and tadpole cells for embryonal rhabdomyosarcoma. However, the so called characteristic cytomorphologic features may not be obvious or may be observed in more than one SRCT. To solve the differential diagnostic problems, ancillary studies like cytochemistry, immunocytochemistry, ultrastructure, flow cytometry, cytogenetics and molecular techniques may be of help. The present case is that of a small round cell lesion of neck in an 11-year-old girl.

Dedifferentiated liposarcoma and pleomorphic liposarcoma

Dedifferentiated liposarcoma (DDLPS) and pleomorphic liposarcoma (PLPS) are distinct high-grade liposarcomas. DDLPS is a nonlipogenic sarcoma characterized by amplification of MDM2 and CDK4. PLPS is a high-grade sarcoma containing lipoblasts, characterized by a complex karyotype and a more aggressive clinical course. Rarely, DDLPS shows lipogenic differentiation, mimicking PLPS. The cytomorphologic features of DDLPS and PLPS and the utility of ancillary studies have not been systemically analyzed. Cytologic preparations of 25 DDLPS and 13 PLPS, all histologically confirmed, were retrospectively reviewed along with clinical and cytogenetic data. Sample cellularity, vascular architecture, background material, predominant cell morphology, quality of the cytoplasm, and nuclear pleomorphism were compared for both tumor types. Immunohistochemistry for MDM2 and CDK4 was performed on cell blocks and/or core needle biopsies. Fine-needle aspirate smears from both DDLPS and PLPS were variably cellular, composed of cellular clusters and noncohesive cells. Abundant myxoid stroma was present in ∼25% of DDLPS and PLPS cases, whereas branching curvilinear vessels were more common in DDLPS than in PLPS (7 of 25 versus 2 of 13). Tumors were composed of predominantly spindled (18 of 25 DDLPS versus 3 of 13 PLPS) or epithelioid cells (7 of 25 DDLPS versus 6 of 13 PLPS). Pleomorphic cells were predominant in 3 PLPS, and were frequent in both (13 of 25 DDLPS versus 10 of 13 PLPS). The cytoplasm was mostly fibrillary and often vacuolated in both entities. Other features included necrosis, mitoses, and a prominent inflammatory infiltrate. The main cytologic differences were the presence of marked pleomorphism, abundant lipoblasts, and cells with microvacuolated cytoplasm in most PLPS. A total of 24 (96%) and 20 (80%) cases of DDLPS expressed MDM2 and CDK4, respectively, whereas none of the PLPS expressed both markers. Six DDLPS tested showed ring or giant marker chromosomes and/or MDM2 amplification by fluorescence in situ hybridization; 2 PLPS had complex karyotypes. DDLPS and PLPS exhibit variable and occasionally overlapping cytologic features. The presence of lipoblasts, cells with microvacuolated cytoplasm, and marked pleomorphism are more suggestive of PLPS, but these characteristics can be present in DDLPS. Coexpression of MDM2 and CDK4 distinguishes DDLPS from PLPS.

Spermatocytic seminoma in a 92-year-old man: report of a case in which SALL4, a potential novel marker for testicular germ cell tumors, was useful for the diagnosis

Spermatocytic seminoma (SS) is a rare testicular germ cell tumor (TGCT), occurring exclusively in the testes. Diagnosis of SS is important because, unlike other testicular tumors, SS must be treated by orchiectomy alone without further adjuvant therapy owing to its inability to metastasize. However, an accurate diagnosis of SS is often difficult given its rarity and the lack of a reliable marker. We report the occurrence of SS in a 92-year-old man—one of the oldest SS patients reported thus far. The patient presented with a painful right scrotal mass, which had been present for 6 months. A computed tomography scan revealed a testicular mass. There was no significant increase in the serum levels of alpha-fetoprotein (AFP) or human chorionic gonadotropin (hCG). A right orchiectomy was performed, which showed a well-circumscribed white-gray mass. A histological examination revealed sheets of non-cohesive cells with little intervening stroma. The tumor consisted of small, medium, and large cells with frequent mitoses, which is suggestive of SS. Whereas common TGCT markers including AFP, hCG, CD30, and placental alkaline phosphatase were all negative, nuclear reactivity for SALL4, a new TGCT marker, and positivity for CD117 (c-kit) finally helped establish the diagnosis of SS. We conclude that SALL4 immunostaining can be helpful for the diagnosis of TGCT when tumors are negative for conventional TGCT markers.

Scirrhous colonic metastasis from lobular carcinoma of breast.

A 68-year-old woman presented complaining of 2months vague abdominal fullness and constipation. She had a history of surgery 5years ago for invasive lobular carcinoma of the left breast. She had good appetite without any severe symptoms such as vomiting, diarrhea, or hematochezia. No abnormal subcutaneous lymph nodes were detected, and blood tests showed no abnormalities including serum tumor markers. Whole-body computed tomography and bone scintigraphy revealed no tumor recurrences. However, endoscopic findings demonstrated a smooth stenotic lesion with submucosal thickening in the transverse colon, but the colonic mucous membrane was grossly normal. The 3-cm-long stenotic lesion was confirmed by colon imaging using water-soluble contrast medium. A biopsy specimen revealed diffuse infiltration of noncohesive malignant cells with round, atypical nuclei from lamina propria to subserosa. Taken together with immunohistochemistry, a diagnosis of metastatic lobular carcinoma from the breast was made, and transverse segmentectomy was done. Colonic metastasis of breast cancer should be included as a differential diagnosis of any abdominal symptoms, even though mild, when patients have a present or previous history of breast cancer.

The Challenging Diagnosis of the Rhabdoid Carcinoma of the Pelvis

Rhabdoid tumor is an uncommon neoplasia characterized by a monotonous population of large, noncohesive cells with vesicular nuclei and large nucleoli. The misleading name was originally suggested because of the striking morphologic resemblance to other skeletal muscle tumors, but neither ultrastructural nor immunohistochemical features support a myogenic origin for this tumor. The rhabdoid tumors of the kidney in pediatric age are characterized by mutation or deletion of 22q11. In adults, tumors with rhabdoid features are uncommon neoplasia reported in different anatomic sites, but their histogenesis is still unclear. We focused on the literature data regarding the rhabdoid features in pelvic and renal tumors, and we describe a carcinoma involving the pelvis and the kidney with exclusive rhabdoid features, which make the anatomical allocation of the tumor difficult. The tumor did not exhibit any similarities to conventional histologic types of renal cell cancer, not even of the sarcomatous type. Tumor cells showed a strong positivity for epithelial markers (AE1/AE3 and CK 8) and for vimentin, whereas they were negative for skeletal and smooth muscle markers. The nuclei of the tumor cells demonstrated a INI1-positive immunohistochemical stain, indicating the lack of mutation or deletion of the 22q11 chromosome. The appropriate diagnosis is that of an extrarenal high-grade rhabdoid carcinoma originating from the urothelium of the renal pelvis. The decision as to whether the tumor arose primarily in the renal parenchyma or in the renal pelvis could be of therapeutic importance. Appropriate immunohistochemical markers can help in the difficult differential diagnosis.

Stable Transfection of E-cadherin Gene into Mouse Embryonic Stem Cells and Its Effects on Adhesive Capacity of Differentiated Cells

BACKGROUND: During the embryonic stage, E-cadherin expression plays a critical role in the formation of hepatic tissue. OBJECTIVE: E-cadherin gene was transfected into mouse embryonic stem cells (ESCs) to observe its effects on adhesive capacity of differentiated cells. DESIGN, TIME AND SETTING: A cytological in vitro observation was performed at the Laboratory of Surgery, First Hospital Affiliated to Sun Yat-sen University between December 2007 and December 2008. MATERIALS: BALB/c mice at gestational 13 days, of clean grade, were provided by Laboratory Animal Center, Sun Yat-sen University. BALB/c mouse ESCs were preserved by professor Huang Bing from the Department of Ophthalmology, Sun Yat-sen University. CMV promoter-containing eukaryotic expression plasmid pEGFP-N1 was gifted by doctor Lu Zhi-yue from Medical College, Sun Yat-sen University. METHODS: Total RNA was extracted from BALB/c mouse fresh hepatic tissue and synthesized into cDNA by reverse transcription (RT). The synthesized cDNA was used as a template to perform a polymerase chain reaction (PCR) that amplifies a targeted fragment. Following double enzyme digestion, pEGFP-E-cadherin plasmids were reconstructed and transfected into mouse ESCs. In vitro differentiation of transfected mouse ESCs was performed. AIN OUTCOME MEASURES: Detection of E-cadherin expression in the differentiation system using RT-PCR and immunocytochemistry and observation of adhesive capacity of differentiated cells. RESULTS: E-cadherin gene-transfected ESCs could stably express E-cadherin during differentiational 1-17 days, while non-transfected ESCs expressed a decreasing amount of E-cadherin. The adhesive capacity of differentiated cells that stably expressed E-cadherin was markedly enhanced. Compact cell connection and multi-layer growth state remained at 19 days. While non-transfected ESCs gradually changed from embryoid bodies into noncohesive cell populations. CONCLUSION: Differentiating E-cadherin ESCs exhibit markedly enhanced adhesive capacity and maintain multi-layer growth state.

Plasmacytoid urothelial carcinoma of the bladder

In this report, we present the clinicopathologic features of 11 cases of the plasmacytoid variant of urothelial carcinoma. This is a rare variant of bladder cancer recognized by the current World Health Organization classification of urologic tumors. The plasmacytoid component varied from 30% to 100% of the tumor specimen; in 8 cases, the plasmacytoid component comprised greater than 50% of the tumor with 2 cases showing pure plasmacytoid carcinoma. The architectural pattern of the tumor varied from solid expansile nests with noncohesive cells to mixed solid and alveolar growth; a streaking discohesive architecture was additionally present in 2 cases (18%). At histology, the individual tumor cells had an eccentrically placed nucleus and abundant eosinophilic cytoplasm reminiscent of plasma cells. Most neoplastic cells had nuclei of low to intermediate nuclear grade with occasional nuclear pleomorphism. Seven of 9 mixed cases had concurrent conventional high-grade urothelial carcinoma, and the remaining 2 cases presented features of nested or micropapillary urothelial carcinoma. Small intracytoplasmic vacuoles were variably present in all cases. All patients had advanced stage cancer (>pT3), and 8 (73%) had lymph node metastasis. Immunohistochemical staining demonstrated that both plasmacytoid and associated conventional urothelial carcinoma were positive for cytokeratins 7, 20, and AE1/AE3 and epithelial membrane antigen; CD138 was positive in 3 cases. Follow-up information was available in all cases (range, 2-16 months; mean, 7 months). Nine of the patients died of disease from 2 to 11 months, and 2 patients were alive with disease at 8 and 16 months. In summary, plasmacytoid variant of urothelial carcinoma is an aggressive variant associated with poor prognosis that presents at an advanced clinical stage. In limited samples, it may be misdiagnosed as chronic cystitis or plasmacytoma, a pitfall further compounded by CD138 expression in some cases. Morphological distinction from other malignant neoplasms with plasmacytoid phenotype is critical for its clinical management.

Paraplegia as the presenting manifestation of extramedullary megakaryoblastic transformation of previously undiagnosed chronic myelogenous leukemia

Extramedullary tumors, also known as granulocytic sarcomas (GS), occur most frequently in acute myelogenous leukemia (AML). They may signal the onset of the accelerated phase of chronic myelogenous leukemia (CML) or the blastic transformation of a myeloproliferative disorder. Occasionally, a GS may be the presenting sign of undiagnosed AML, and rarely the presenting sign of undiagnosed CML or aleukemic leukemia. Paraplegia due to a spinal cord GS is an extremely rare presentation of undiagnosed leukemia. This is the first case report of paraplegia as the presenting manifestation of extramedullary megakaryoblastic transformation of previously undiagnosed CML. A 53-year-old woman reported back pain for 6 days, rapidly progressing to paraplegia. Physical examination noted a large abdominal mass and flaccid paralysis in both lower extremities. Spinal MRI revealed a T4-T6 vertebral mass causing spinal stenosis and cord compression. Tumor debulking and laminectomy were performed emergently. The tumor consisted of noncohesive blast cells. The CBC revealed a leukocyte count of 238,300/microl and a differential consistent with CML. Reexamination of the patient found that the abdominal mass was a giant spleen. Further immunohistochemical studies of the tumor were consistent with extramedullary acute megakaryoblastic blast transformation of CML. Although extramedullary blast crises herald the accelerated phases in approximately 10% of CML cases, megakaryoblastic blast transformation of CML accounts for less than 3% of these cases. The combination of acute paraplegia and megakaryoblastic transformation in a previously undiagnosed patient with CML is extremely rare and may pose a diagnostic dilemma.

Cytological evaluation of head and neck tumors in children—A pattern analysis

A total of 135 pediatric head and neck tumors diagnosed in our institute were reviewed with a view to elucidate the overall cytological patterns and analyze the important cytological features. Ninety-four tumors (69.6%) were aspirated for a primary diagnosis, and in 41 (30.4%) cases, fine-needle aspiration cytology was performed to document relapse, recurrence or a metastasis. Among the 94 tumors aspirated for a primary diagnosis, 66 cases (70.2%) were accurately diagnosed, in 22 cases (23.4%) a broad working diagnosis was offered, and 6 cases (6.4%) were misdiagnosed. The accuracy rate was higher (79.3%) when relapse-recurrent and metastatic tumors were included. The smears were broadly divided into six patterns, viz. round cell, epithelial, anaplastic, giant cell, mixed inflammatory, and spindle cell patterns. The round cell pattern was the most frequent one encountered in this group. The cytological features that stood the test of variability were lymphoglandular bodies and a noncohesive cell population in hematolymphoid malignancies, pale chromatin and cytoplasmic vacuoles in primitive neuroectodermal tumor/Ewing's sarcoma (PNET/ES), neuropil and rosettes in neuroblastoma, and plasmacytoid rhabdomyoblasts in rhabdomyosarcoma. A fairly good accuracy was seen in the diagnosis of metastatic undifferentiated carcinoma and anaplastic lymphoma, but the giant-cell and spindle-cell tumors continued to pose a problem in diagnosis. Ancillary techniques such as immunocytochemistry and electron microscopy applied in limited cases helped evaluate Langerhans cell histiocytosis, alveolar rhabdomyosarcoma, and the PNET/ES family of tumors.

Undetected invasive lobular carcinoma of the breast: review of false-negative smears.

Analysis of a series of 34 fine-needle aspirations (FNA) from 28 patients with invasive lobular carcinoma (ILC) was undertaken. The false-negative smears were reviewed to reveal the cause of such a relatively frequent error. This was a retrospective study and comparison between the cytological and pathological findings in a series of 34 FNA. Three cases were excluded without sufficient material. Twelve cases were positive, nine suspicious of malignancy, and 10 were considered false-negatives. In a second analysis of this later group, one was reclassified as carcinoma, two reconsidered without sufficient material for diagnosis, and the remaining seven, still considered negatives, constituted the core of this study. Of these seven, there were none with hypercellular smears and in six there was a predominance of fat-tissue fragments. The scarce epithelial component showed honeycomb-flat sheets in four, loose clusters in three, small and tight clusters with irregular limits in six, and more than 10% of isolated epithelial cells (noncohesive cells) in one case. "Staghorns" were undetected and myoepithelial cell nuclei were very scarce in all cases. Some nuclear enlargement was detected in one, angulated nuclear contour in three, and nuclear crowding was present in five. All seven had fine, homogeneous chromatin, without prominent nucleoli. Cytoplasmic limits were undefined in all but one (6/7) and occasional cytoplasmic vacuolization was detected in two. Hypocellular smears with few, small, and dense groups (but always with more than 10 groups in at least one smear) can be related with ILC. In these cases, further studies are recommended to exclude malignancy. The loose cluster and flat sheets identified in four cases represent a benign epithelial hyperplasia mixed with the ILC.

Cytologic diagnosis of malignant mesothelioma, with particular emphasis on the epithelial noncohesive cell type.

The effusion cytologies from 21 cases of malignant mesothelioma (MM) (15 pleural, 6 peritoneal) diagnosed at the Indiana University Medical Center during 1990-1997 were reviewed. Using the classification of Tao (Acta Cytol 1979;23:209-213), 13 cases of MM were of the epithelial cohesive cell type and 8 were of the epithelial noncohesive cell type. While the epithelial cohesive cell type has been discussed in the literature, the epithelial noncohesive cell type has not. The cytomorphologic features for both types are presented with particular emphasis on the noncohesive cell type. The differential diagnosis and use of ancillary confirmatory laboratory tests are briefly discussed. Because of its resemblance to florid reactive mesothelial hyperplasia and the general lack of awareness of the existence of the single-cell pattern of mesothelioma, this diagnosis can often be missed.

Cytologic diagnosis of malignant mesothelioma, with particular emphasis on the epithelial noncohesive cell type

The effusion cytologies from 21 cases of malignant mesothelioma (MM) (15 pleural, 6 peritoneal) diagnosed at the Indiana University Medical Center during 1990–1997 were reviewed. Using the classification of Tao (Acta Cytol 1979;23:209–213), 13 cases of MM were of the epithelial cohesive cell type and 8 were of the epithelial noncohesive cell type. While the epithelial cohesive cell type has been discussed in the literature, the epithelial noncohesive cell type has not. The cytomorphologic features for both types are presented with particular emphasis on the noncohesive cell type. The differential diagnosis and use of ancillary confirmatory laboratory tests are briefly discussed. Because of its resemblance to florid reactive mesothelial hyperplasia and the general lack of awareness of the existence of the single-cell pattern of mesothelioma, this diagnosis can often be missed. Diagn. Cytopathol. 1999;20:57–62. © 1999 Wiley-Liss, Inc.