Visible Nucleoli Research Articles

Evaluation of an anal sac adenocarcinoma tumor in a Spitz dog

A 9-year-old emasculated male Spitz with tenesmus and constipation had a subcutaneous mass at the left ventral aspect of the anus with history of polyuria and polydipsia. A complete blood cell count, serum biochemistry panel, and urinalysis (cystocentesis sample) were evaluated. Abnormalities in the serum biochemistry panel included a mildly elevated serum cholesterol concentration (7.28 mmol/L; reference interval, 2.70-5.94 mmol/L), increased serum alkaline phosphatase activity (184 U/L; reference interval, 9-90 U/L), alanine transaminase (122 U/L; reference interval, 5-60 U/L) activity and aspartate aminotransferase (80 U/L; reference interval, 5-55 U/L) activity, severe increased total calcium concentration (16.3 mg/dL; reference interval, 8.2-12.4 mg/dL or 9.3-11.4 mg/dL), and decreased total calcium concentration (3.4 mg/dL, reference interval, 2.5-5.6mg/dL). Furthermore, testing revealed an increased intact parathyroid hormone concentration (38.6 pmol/L; reference interval, 3-17 pmol/L). On cytologic and histopathologic examinations, various types of cells were observed. Most of the cells were oval to polygonal and had elliptical or elongate nuclei and a moderate amount of pale to basophilic cytoplasm. The remaining cells had round to oval nuclei and pale to basophilic cytoplasm. Cells of both types were loosely adhered to each other and were arranged in rosette-like structures. Both neoplastic cell types had fine homogenous chromatin and either a small indistinct nucleolus or no visible nucleolus. Mild anisokaryosis and anisocytosis were observed. Histologically, the mass consists of glandular structures formed by cuboidal cells admixed with bundles of spindle cells. Based on location and histologic features, the final diagnosis was adenocarcinoma of the apocrine gland of the anal sac, which should be included as a cytologic differential diagnosis when spindle cells and typical epithelial cells are observed in masses in the region of the anal sac of dogs.

Adventitious root formation in olive (Olea europaea L.) microshoots: anatomical evaluation and associated biochemical changes in peroxidase and polyphenol oxidase activities

SummaryTrials were performed using in vitro-cultured microshoots of the olive (Olea europaea L.) cultivar ‘Galega vulgar’, as initial explants, to identify histological events and modifications in peroxidase and polyphenol oxidase activities during adventitious root formation. Explant bases were submitted to a 10 s quick-dip treatment to promote rooting, using a sterile solution of 14.7 mM indole-3-butyric acid (IBA). Samples for histology and quantification of enzyme activities were collected at pre-established periods from 0 to 720 h. The first signs of modifications in stem cell morphology were observed 96 h after explant inoculation on olive culture medium (OM), with some cortical cells showing a dense cytoplasm and a large central nucleus, with visible nucleoli. The first mitotic events were observed after 144 h and evolved via two different pathways: non-specific cell division, leading to callus formation; and organised cell division, leading to the formation of root meristemoids. After 456 h, the first organised root primordia became visible. No root formation was achieved without earlier callus development, and 89% of root primordia originated from tissues other than cambial/phloem tissue. Peroxidase and polyphenol oxidase activities were recorded throughout the whole rooting process. The first significant modification in enzyme activity, with a drop from 0.19 to 0.14 ΔA490 units min–1 50 mg–1 of explant material, was observed for peroxidase within the first 4 h after IBA treatment. Subsequent changes in both enzyme activities could be correlated with different phases of the adventitious rooting process.

Acquired Philadelphia Chromosome with Transformed Myelodysplastic Syndrome

Journal of Case Reports in Medicine,2013,2,1,1-2.Published:April 2013Type:Case ReportAuthors:Yoshinobu Saito, Naoto Takahashi, Hideaki Ohyagi, Yoshinori Shinohara, Masaaki Kume, and Kenichi Sawada Author(s) affiliations:Yoshinobu Saito,1 Naoto Takahashi,2 Hideaki Ohyagi,1,2 Yoshinori Shinohara,1,2 Masaaki Kume,1 and Kenichi Sawada2 1Department of Hematology, Hiraka General Hospital, 3-1, Maego Aza Yatsuguchi, Yokote City, 013-8610, JAPAN. 2Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita City, 010-8543, JAPAN. Abstract:Transformation to acute myeloid leukemia (AML) frequently occurs in patients with myelodysplastic syndrome (MDS), and genetic evolution probably plays a critical role in this transformation. However, late appearance of the Philadelphia (Ph) chromosome during the course of transformed MDS is extremely rare. We report a 77-year-old man with transformed MDS and an acquired Ph chromosome. He was initially diagnosed with refractory anemia with 45,XY,del(5)(q?),-7,-14,-17,+mar1,+mar2 [7/20] as the major clone. After 4 months, hematological studies showed progression of anemia with increased number of blast cells. Conventional chromosome analysis revealed 45,XY,del(5)(q?),-7, t(9;22)(q34;q11.2),-14,-17,+mar1,+mar2 [20/20], a subclone with an acquired Ph chromosome derived from a stem clone observed at MDS diagnosis. RT-PCR results were positive for major BCRABL transcript. Although a comparison of whole-genome sequences between original and transformed clones would be informative, the acquired Ph chromosome probably played a role as a “class-I mutation,” which increases cell proliferation in transformed MDS. Keywords:Philadelphia chromosome; Myelodysplastic syndrome; Acute myeloid leukemiaView:PDF (582.63 KB) PDF Images Figure 1: Bone marrow morphology and G-banding revealed clonal evolution. (a) Bone marrow smear (Wright- Giemsa, 1,000×) showed MDS at diagnosis. (b) Karyotype at MDS diagnosis was 46,XY,del(5)(q?)[1]/45,XY,idem, -7,-14,-17,+mar1,+mar2[7]/45,XY,-5[4]/46,XY[8]. A major abnormal clone is shown in Figure 1(b). (c) Bone marrow smear (Wright-Giemsa, 1,000×) showed AML with multilineage dysplasia upon progression of anemia 4 months after MDS diagnosis. The size of the blast cells ranged from medium to large; they showed a high nuclear:cytoplasmic ratio and visible nucleoli. (d) Karyotypes at diagnosis of transformation to AML was 45,XY,del(5)(q?),-7,t(9;22)(q34;q11.2),-14,-17, +mar1,mar2[20]. The Philadelphia chromosome is marked by an arrowhead.

Progressive Diplopia and Facial Weakness in a 62-Year-Old Woman

Progressive Diplopia and Facial Weakness in a 62-Year-Old Woman

Glandular trichomes in <i>Connarus suberosus</i> (Connaraceae): distribution, structural organization and probable functions.

Connarus suberosus is a typical species of the Brazilian Cerrado biome, and its inflorescences and young vegetative branches are densely covered by dendritic trichomes. The objective of this study was to report the occurrence of a previously undescribed glandular trichome of this species. The localization, origin and structure of these trichomes were investigated under light, transmission and scanning electron microscopy. Collections were made throughout the year, from five adult specimens of Connarus suberosus near Botucatu, São Paulo, Brazil, including vegetative and reproductive apices, leaves and fruits in different developmental stages, as well as floral buds and flowers at anthesis. Glandular trichomes (GTs) occurred on vegetative and reproductive organs during their juvenile stages. The GTs consisted of a uniseriate, multicellular peduncle, whose cells contain phenolic compounds, as well as a multicellular glandular portion that accumulates lipids. The glandular cell has thin wall, dense cytoplasm (with many mitochondria, plastids and dictyosomes), and a large nucleus with a visible nucleolus. The starch present in the plastids was hydrolyzed during the synthesis phase, reducing the density of the plastid stroma. Some plastids were fused to vacuoles, and some evidence suggested the conversion of plastids into vacuoles. During the final activity stages of the GTs, a darkening of the protoplasm was observed in some of the glandular cells, as a programmed cell death; afterwards, became caducous. The GTs in C. suberosus had a temporal restriction, being limited to the juvenile phase of the organs. Their presence on the exposed surfaces of developing organs and the chemical nature of the reserve products, suggest that these structures are food bodies. Field observations and detailed studies of plant-environment interactions, as well as chemical analysis of the reserve compounds, are still necessary to confirm the role of these GTs as feeding rewards.

Adult rhabdomyoma: A challenging diagnosis on cytology

Adult rhabdomyoma: A challenging diagnosis on cytology

Cytologically atypical anal sac adenocarcinoma in a dog

A 10-year-old intact female Shetland Sheepdog with tenesmus had a subcutaneous mass at the left ventral aspect of the anus. On cytologic examination, 2 types of cells were observed. Most of the cells were oval to polygonal and had elliptical or elongate nuclei and a moderate amount of pale to basophilic cytoplasm. The remaining cells had round to oval nuclei and pale to basophilic cytoplasm. Cells of both types were loosely adhered to each other and were arranged in rosette-like structures. Both neoplastic cell types had fine homogenous chromatin and either a small indistinct nucleolus or no visible nucleolus. Mild anisokaryosis and anisocytosis were observed. Histologically, the mass consists of glandular structures formed by cuboidal cells admixed with bundles of spindle cells. Eosinophilic PAS- and Alcian blue-positive secretory material was found in the center of some glandular structures. Both neoplastic cell types had positive staining with paradoxical concanavalin A and expressed cytokeratin, but not vimentin, S-100, α-smooth muscle actin, or desmin. Based on location and histologic and immunohistochemical features, the final diagnosis was adenocarcinoma of the apocrine gland of the anal sac, which should be included as a cytologic differential diagnosis when spindle cells and typical epithelial cells are observed in masses in the region of the anal sac of dogs.

Recurrent anaplastic medulloblastoma in cerebrospinal fluid after autologous hematopoietic stem cell transplant

Cerebrospinal fluid (CSF) dissemination can be seen relatively frequently in medulloblastomas and its presence at diagnosis is important for determining both treatment and prognosis. The anaplastic variant is an aggressive variant of medulloblastoma with characteristic histopathologic features and unfavorable prognosis that was included in the latest WHO classification. Herein, we report the CSF cytologic features of a case of recurrent anaplastic medulloblastoma in a 17-year-old male patient who had undergone autologous hematopoietic stem cell transplant as a part of the treatment protocol. The malignant cells were large, had high nucleocytoplasmic ratios, and highly pleomorphic, frequently polylobated nuclei with coarse chromatin and 1-3 visible nucleoli. These CSF cytologic features differed significantly from those of classic medulloblastoma, which usually shows small cells with rounded, rather uniform nuclei with fine ("blastic") chromatin. The differential diagnosis of anaplastic medulloblastoma is broader than that of classic medulloblastoma, as it includes metastatic carcinomas and large cell lymphoma, a differential diagnosis especially pertinent in this patient with a history of autologous hematopoietic stem cell transplant. Awareness of these unusual but distinctive cytologic features is important for the accurate diagnosis of anaplastic medulloblastomas in CSF specimens and to avoid possible diagnostic pitfalls.

Blastic plasmacytoid dendritic cell neoplasm presenting as fever with diffuse cutaneous nodules

A young man, presented with high-grade fever and disseminated asymptomatic skin lesions of 6-weeks duration. Cutaneous examination revealed multiple infiltrated monomorphic skin-colored papules and nodules upto 2×2 cm all over scalp, face, trunk and extremities. Light microscopy of nodules showed diffuse infiltration of dermis and subcutis by a tumor composed of medium to large cells with round to ovoid nuclei with fine chromatin, few with visible nucleoli and scanty to moderate amounts of eosinophilic cytoplasm. Tumor cells were positive for CD4, CD8, CD56 and negative for CD30, terminal deoxynucleotidyl transferase and Alk-1. Excised axillary lymph node showed similar morphologic and immunohistochemical findings. There was bone marrow involvement with infiltrate of large atypical/immature lymphoid cells. Diagnosis of blastic plasmacytoid dendritic cell neoplasm was made. This is a rare neoplasm. presenting commonly in the skin, with or without concurrent extracutaneous disease.

Production of Giant Mouse Oocyte Nucleoli and Assessment of Their Protein Content

Compared with advanced developmental stage embryos and somatic cells, fully grown mammalian oocytes contain specific nucleolus-like structures (NPB - nucleolus precursor bodies). It is commonly accepted that they serve as a store of material(s) from which typical nucleoli are gradually formed. Whilst nucleoli from somatic cells can be collected relatively easily for further biochemical analyses, a sufficient number of oocyte nucleoli is very difficult to obtain. We have found that isolated oocytes nucleoli fuse very efficiently when contact is established between them. Thus, well visible giant nucleoli can be obtained, relatively easily handled and then used for further biochemical analyses. With the use of colloidal gold staining, we estimated that a single fully grown mouse oocyte nucleolus contains approximately 1.6 ng of protein. We do believe that this approach will accelerate further research aiming at analyzing the composition of oocyte nucleoli in more detail.

Pulmonary Myxoma in a Sheep

Pulmonary myxomas are rare in domestic animals and only two cases have been reported previously in sheep. An 8 x 6 x 4 cm mass was detected in the diaphragmatic lobe of the right lung of a 4-year-old Persian Karakul ewe. The mass was well demarcated, multilobulated, soft in consistency and white in colour. The cut surface exuded a mucoid substance and a distinct capsule was evident. Microscopically, the tumour comprised a hypocellular myxomatous matrix, rich in acid mucopolysaccharides, with scattered spindle-shaped or stellate cells. These cells had uniform, oval-shaped nuclei without visible nucleoli and expressed vimentin and S100 on immunohistochemical examination. These gross, microscopical and immunohistochemical features are characteristics of myxoma.

Striking bone marrow plasmacytosis in a patient with sickle cell anaemia

A 48-year-old black African man with known sickle cell anaemia presented with a 3-week history of general lethargy and shortness of breath. He also admitted to a productive cough with yellow sputum, 7 kg weight loss and drenching night sweats. He was pyrexial, with tachycardia, an ejection systolic murmur and bilateral basal crepitations. He also had a tender enlarged liver, 3 cm below the right costal margin. Blood count showed pancytopenia (haemoglobin concentration 45 g/l, neutrophil count 1·6 × 109/l, platelet count 62 × 109/l) and macrocytosis (mean cell volume 104 fl) with an inappropriately blunted reticulocyte response (reticulocyte count 72 × 109/l). A blood film showed the typical features of sickle cell anaemia. A chest radiograph showed diffuse bilateral extensive nodular shadowing with a negative sputum stain for acid-fast bacilli. A bone marrow aspirate showed some haemophagocytosis and, although overall plasma cells were 5–10%, there were large clumps of these cells adjacent to fragments, some with features of immaturity, such as visible nucleoli or lack of chromatin condensation (left panel). Bone marrow trephine biopsy sections showed hypercellularity with granulomas and acid fast bacilli being demonstrated on an auramine stain. In addition 50% of bone marrow cells were plasma cells (right panel, immunoperoxidase for CD138). These showed a normal kappa: lambda ratio and serum protein electrophoresis showed a marked polyclonal increase in immunoglobulin (Ig)G and IgA without any paraprotein. Following detection of acid-fast bacilli in the trephine biopsy sections, anti-tuberculosis treatment was started and culture of the sputum sample subsequently grew Mycobacterium tuberculosis. The pancytopenia resolved on treatment. It is rare for such a striking increase to be detected in plasma cells in infection, although similar observations have previously been made in syphilis. Because of the overall clinical picture, we suspected infection as the cause of the plasmacytosis rather than a plasma cell neoplasm. It is important to be aware that a very marked increase in plasma cells does not necessarily indicate multiple myeloma.

Clinical evaluation of canine mast cell tumor treatment between combined vinblastine and prednisolone and single prednisolone

Thirty three dogs having cutaneous mast cell tumors (MCT) were divided into two groups; group 1 had 23 dogs that were treated with vinblastine and prednisolone and group 2 had 10 dogs that were treated with prednisolone. Evaluation of the 33 pre- and post-treated tissue samples was performed on their clinical stages, histopathological features, expression of proliferative markers such as argyrophilic nucleolar organizer regions (AgNORs), proliferative cell nuclear antigen (PCNA) and Ki-67 and clinical response. All cases were diagnosed as MCT grade II without post-treatment changes in histopathological grade. An increase of uniform nucleus, stroma but a decrease of cytoplasm, the number of visible nucleolus, intralesional vascularization, eosinophilic aggregation, and the mean of mitotic index (pretreatment = 1.6 cells/HPF, post-treatment = 1.1 cells/HPF) was observed in the post-treated samples of both groups. With regard to the clinical evaluation, 18 dogs (78.2%) were partially responsive and the rest (21.8%) were stable in group 1 while five dogs (50%) were partially responsive, three dogs (30%) were stable, and the remaining two dogs (20%) were progressive in group 2. The median survival time of the group 1 cases was 101 days and for the group 2 cases was 175 days. In addition, mean ± standard deviations of AgNORs (dots/cell), PCNA (%), and Ki-67 (%) were 1.83 ± 0.4, 18.67 ± 9.25, and 6.86 ± 7.23 in the pretreatment group 1 and 1.59 ± 0.3, 12.4 ± 7.15, and 1.9 ± 1.35 in the post-treatment group 1, respectively. Mean ± standard deviations of AgNORs, PCNA and Ki-67 were 1.83 ± 0.42, 18 ± 20.01 and 6.74 ± 5.42 in the pretreatment group 2 and 1.67 ± 0.28, 6.28 ± 5.59 and 2.3 ± 1.55 in the post-treatment group 2, respectively. All proliferative markers decreased differently statistically after treatment (P < 0.05). In conclusion, the MCT dogs treated with vinblastine and oral prednisolone and single oral prednisolone were shown to have a decrease in histopathological malignancy characteristics which included AgNORs, PCNA, Ki-67 indices.

Establishment and characterization of a cell line (IGSK-3) secreting human chorionic gonadotropin, adrenocorticotropic hormone and parathyroid hormone-related protein derived from primary poorly differentiated adenocarcinoma of the stomach

We recently established human chorionic gonadotropin-, adrenocorticotropic hormone- and parathyroid hormone-related protein-secreting cell line derived from primary poorly differentiated adenocarcinoma of the stomach. The cell line was designated as IGSK-3. Inverted-phase contrast microscopy revealed that the IGSK-3 cells consist of two morphological subtypes. One type has visible nucleoli and clear nuclei, but nucleoli and nuclear membrane of the other type are invisible. The population-doubling time was about 43 h. An analysis of conditioned medium by IGSK-3 cells cultured for 4 days revealed the IGSK-3 cells secrete human chorionic gonadotropin-beta (0.5 ng/mL), adrenocorticotropic hormone (5.5 pg/mL), parathyroid hormone-related protein (3.4 pmol/mL) and epidermal growth factor (14.2 pg/mL). Histopathological diagnosis of the graft of IGSK-3 cells revealed that IGSK-3 cells built a poorly differentiated adenocarcinoma which resembled the original tumor. In addition, the IGSK-3 cell line was immunocytochemically positive for human chorionic gonadotropin-beta and epidermal growth factor receptor, and negative for vascular endothelial growth factor.

Aberrant Diffuse Expression of p63 in Adenocarcinoma of the Prostate on Needle Biopsy and Radical Prostatectomy: Report of 21 Cases

Aberrant diffuse expression of p63 in prostate carcinoma cells is a rare and poorly understood phenomenon. We studied 19 cases of prostate cancer with aberrant diffuse expression of p63 on needle biopsy and reviewed the subsequent radical prostatectomies in 6 cases. In 19/21 cases, 100% of the cancer nuclei stained intensely for p63, with 70% staining in the remaining 2 cases. Two additional radical prostatectomies with aberrant p63 staining with no needle biopsies available for review were also analyzed. On the hematoxylin and eosin-stained slides, 19/21 cases (90.5%) showed a distinctive morphology composed predominantly of glands, nests, and cords with atrophic cytoplasm, hyperchromatic nuclei, and visible nucleoli. Needle biopsy cases ranged from Gleason patterns 3 to 5 with tumor identified on one or more cores, ranging from a minute focus to 80% of the core. In all 8 radical prostatectomies p63 positive cancer was present, with in 2/8 cases both p63 positive cancer and usual p63 negative acinar prostate cancer. In all 8 cases, the tumors were organ confined with negative margins and there was no seminal vesicle involvement or lymph node metastasis. The presence of p63 positive atypical glands with an infiltrative pattern and perineural invasion on radical prostatectomy confirmed the needle biopsy diagnosis of carcinoma. Rarely, prostate cancer can aberrantly express diffuse p63 staining in a nonbasal cell distribution leading to the erroneous diagnosis of atrophy or atypical basal cell proliferation. The diagnosis of prostate cancer is based on the morphology and confirmed by the absence of high molecular weight cytokeratin staining and positivity for alpha-methylacyl-CoA racemase in the atypical glands. Pathologists need to be aware of this rare and unusual phenomenon, which is a potential pitfall in prostate cancer diagnosis.

APC/CCdc20 Controls the Ubiquitin-Mediated Degradation of p21 in Prometaphase

During the G1/S transition, p21 proteolysis is mediated by Skp2; however, p21 reaccumulates in G2 and is degraded again in prometaphase. How p21 degradation is controlled in mitosis remains unexplored. We found that Cdc20 (an activator of the ubiquitin ligase APC/C) binds p21 in cultured cells and identified a D box motif in p21 necessary for APC/C(Cdc20)-mediated ubiquitylation of p21. Overexpression of Cdc20 or Skp2 destabilized wild-type p21; however, only Skp2, but not Cdc20, was able to destabilize a p21(D box) mutant. Silencing of Cdc20 induced an accumulation of p21, increased the fraction of p21 bound to Cdk1, and inhibited Cdk1 activity in p21(+/+) prometaphase cells, but not in p21(-/-) cells. Thus, in prometaphase Cdc20 positively regulates Cdk1 by mediating the degradation of p21. We propose that the APC/C(Cdc20)-mediated degradation of p21 contributes to the full activation of Cdk1 necessary for mitotic events and prevents mitotic slippage during spindle checkpoint activation.

No differences in calcium-binding protein immunoreactivity in the posterior cingulate and visual cortex: Schizophrenia and controls

Schizophrenia-specific alterations in the densities of interneurons immunoreactive (ir) to the calcium binding proteins are reported for several cortical regions. However, no reported studies have searched for such differences within the posterior cingulate cortex using antibodies to a specific calcium binding protein, calbindin (Cb). Aims: Compare the (a) relative density of Cb-ir neurons (ratio of labeled neurons to total neurons), (b) relative width of cortical layers II/III and (c) somal areas of Cb-ir neurons in people with schizophrenia and non-psychiatric age-, gender- and postmortem index-matched controls (9 per group). Method: Tissue from Brodmann's area (BA) 30 and 23 and an internal control region, the visual cortex (BA 18) were labeled with polyclonal Cb antibodies then Nissl counter-stained. Cb-ir neurons as well as counter-stained neurons with clearly visible nucleoli were plotted and counted within their area1 and laminar boundaries. Results: No qualitative or statistical differences in the relative density of Cb-ir neurons were observed. A trend towards a significant effect was detected in BA 30, the relative density of Cb-ir neurons for controls was greater than for schizophrenics ( P = 0.0518). There were no significant differences in the relative cortical widths or somal areas. The data from this study suggest that the posterior cingulate cortex may not be involved in schizophrenia, at least not as far as Cb-ir neurons are concerned.

Trichoepithelioma With Giant and Multinucleated Neoplastic Epithelial Cells

We report an unusual example of trichoepithelioma containing giant and multinucleated cells in the epithelial compartment. The patient was a 52-year-old woman who presented with a solitary nodule on the scalp measuring 2 cm of apparently long duration. The biopsy revealed a typical trichoepithelioma. The unusual feature was the presence in some epithelial nodules of large epithelial cells with hyperchromatic nuclei and no visible nucleoli that exceed 3 to 5 times the adjacent follicular germinative cells. Often, multinucleated cells were seen. Rare nodules were almost entirely composed of giant/multinucleated cells. The majority of the nodules containing giant cells were situated in the deeper portion of the neoplasm. No mitoses were seen in these giant cells. No enlarged or multinucleated cells were seen in the stroma. The neoplastic epithelial cells were diffusely reactive for bcl-2, including the giant and multinucleated cells. The proliferating rate was low; Ki-67 stained some giant cells. CD34 stained the stroma. We believe that the focal presence of pleomorphic giant cells in trichoepithelioma has no clinical or prognostic implications and does not denote its "malignant transformation".

Morphology of Healthy Human Parathyroid Glands in Cytologic Smears

To compare the morphology of different parenchymal cell types in healthy human parathyroid glands (HPGs) in cytologic smears with their structure on histologic sections and to establish criteria for their recognition in smears.The HPGs of 47 subjects (27 females and 20 males) were incidentally removed during surgery on the thyroid gland. The tissue of glands with a normal macroscopic and microscopic appearance was analyzed in cytologic smears and on histologic sections.In cytologic smears (as well on histologic sections), dark and light chief cells predominated. Dark chief cells, which were more numerous than light ones, had a smaller nucleus without a visible nucleolus. The nucleus of light chief cells was larger with 1 or 2 nucleoli visible. The cytoplasm of both types of chief cells was poorly defined, grey-blue and often vacuolated. In the smears, the cytoplasm of oxyphilic cells was dense, gray-rose and well defined. In dark oxyphilic cells, the nuclei were smaller and without a visible nucleolus. Light oxyphilic cells had a larger nucleus and visible nucleolus.The identification and distribution of 4 parenchymal cell subtypes in the smears of pathologically altered HPGs may yield insights into the possible role of these cells in a specific disease.

Myofibroblastoma-like changes in fibro(stromo)-epithelial lesions of the breast: report of two cases

Sir, Apart from the well-known epithelial/stromal tumors of the breast, such as fibroadenoma and phylloides tumors, another group of biphasic lesions, showing a wide morphological spectrum on a common basic theme, does exist. These lesions have been variably termed “fibroepithelial tumors,” “hamartomas,” “fibroadenoma variants,” and “stromo-epithelial lesions” [1, 2, 3, 6]. The epithelial component usually features florid/sclerosing adenosis and ductal epithelial hyperplasia. The stromal component is usually composed of fibrous tissue in which mature lipomatous or cartilaginous or osseous components (hamartoma) may be occasionally encountered [6]. Although there is the possibility that stroma may also display a variable fibro/myofibroblastic and myoid differentiation [2, 3], to the best of our knowledge, myofibroblastomalike changes have not been reported in mammary fibroepithelial (hamartomas) lesions. Two women (25 years and 49 years) presented with two nodular breast masses, measuring 1.5 cm and 2 cm in greatest dimension, respectively, which were surgically excised with the pre-operative diagnosis of fibro-adenoma. Histologically, both surgical samples showed the typical features of the so-called “fibro-epithelial lesion,” being composed of an admixture of glandular and stromal component proliferation. The epithelial component consisted of florid and sclerosing adenosis admixed with foci of typical ductal hyperplasia. In both cases, the stroma was completely replaced by bland-looking oval to spindle cells with pale to slightly eosinophilic cytoplasm, arranged in short irregularly intersecting fascicles, interrupted by thick bands of brightly eosinophilic collagen (Fig. 1A, B). Sometimes cells were nested grouped and similarly surrounded by thick collagen bands (Fig. 1C). Cells had round to spindle-shaped nuclei with one or two visible nucleoli (Fig. 1B). These stromal changes were closely reminiscent of myofibroblastoma, typical type, of the breast. Immunohistochemically, the cells of both cases had a similar profile: diffuse and strong immunoreactivity to vimentin and a-smooth-muscle actin (Fig. 1D) and focal staining to desmin, CD34, and bcl-2 protein. No staining was obtained for calponin, h-caldesmon, and S100 protein. This immunophenotype, similar to what is observed in breast myofibroblastoma, is consistent with the fibro/myofibroblastic differentiation of stromal cells. It is well known that mammary stroma has the capability of modulating its cellular phenotype as well as its extracellular matrix components upon several pathological conditions. As tumors of mammary stroma (fibroadenoma, myofibroblastoma, solitary fibrous tumor, leiomyoma), fibro(stromo)-epithelial lesions are examples in which presumptive fibroblast-like mammary stromal stem cells may undergo multidirectional mesenchymal differentiation [4, 5]. This event may well explain the occurrence of a stromal fibromatosis-like fibro/myofibroblastic and/or myoid (leiomyomatous) differentiation in these lesions [2, 3]. The present study provides evidence that mammary stromal cells in fibro-epithelial lesions may also acquire morphological and immunohistochemical features similar to those observed in myofibroblastoma, supporting the hypothesis that such cells (interlobular? and/or intralobular?) are the precursors of myofibroblastoma. Similar myofibroblastoma-like stromal changes have been reported in the more cellular areas of “pseudoangiomatous stromal hyperplasia,” a lesion which is thought to be histogentically related to myofibroblastoma [7]. Although the characteristic slit-like spaces of this lesion are lacking in our cases, the possibility that we are dealing with a nodular, cellular variant of pseudoangiomatous stromal hyperplasia cannot be completely ruled out. G. Magro ()) Dipartimento G.F. Ingrassia, Anatomia Patologica, Universit di Catania, 95123 Catania, Italia e-mail: g.magro@unict.it Tel.: +39-95-3782024 Fax: +39-95-3782023