Granular Chromatin Pattern Research Articles

Cytologic diagnosis and differential diagnosis of histiocytic signet ring cells in effusion specimens.

Benign histiocytic proliferation in effusion specimens can be found in a variety of diseases such as rheumatoid arthritis, systemic lupus erythematosus, microorganism infections, trauma, reactive eosinophilic pleuritis, and others. In addition, nodular histiocytic/mesothelial hyperplasia is another well-recognized rare cause. The previous studies have shown that proliferative histiocytes have raisinoid nuclei and abundant eosinophilic granular cytoplasm and can be confused with malignant lesions, especially metastatic carcinomas. In this study, we evaluated the cytomorphology of benign histiocytes, discussed the diagnosis and differential diagnosis, and the clinical significance of histiocytic signet ring cells in effusion cytology. Seven hundred and fifty-five benign effusion cases (433 pleural effusions and 322 abdominal fluids) were found over 1 year. Among benign cases, 35 cases (28 pleural effusions and seven abdominal fluids) were included with findings of dominantly histiocytic signet ring cell morphology as well as immunohistochemical (IHC) stains. The clinical findings were also correlated. In contrast to the well-documented cytomorphology of raisinoid nuclei and eosinophilic cytoplasm of proliferative histiocytes in previous studies, we find that these cells predominately presented as signet ring cell morphology with clear cytoplasm. The most characteristic findings of benign histiocytes in pleural effusions are: (1) cells are arranged in sheets and/or scattered individual cells, but no two- or three-dimensional cell clusters; (2) cells are intermediate in size and with normal N/C ratio; (3) cells have eccentric located nuclei and abundant clear cytoplasm, giving signet ring cell appearance; (4) nuclei have fine granular chromatin pattern, no hyperchromia or coarse chromatin pattern, no nuclear atypia; and (5) immunohistochemical (IHC) stains demonstrate a strongly positivity for macrophage-histiocyte lineage marker CD68, but negativity for epithelial markers and mesothelial markers. Clinically, these patients do not demonstrate nodularity or lesions in the mesothelial lining of serous cavities. Our study provides a detailed characterization of benign histiocytic signet ring cells in effusion cytology. The differential diagnosis of histiocytic signet ring cells is broad. The most important differential diagnoses are metastatic adenocarcinoma and epithelioid signet ring cell mesothelioma. The accurate diagnosis is critical for the appropriate clinical management of the patient. Cytopathologists should be aware of the diagnostic pitfalls of benign histiocytic signet ring cells in effusion samples in daily practice.

S3421 HIV/AIDS, and MAC vs COVID Diarrhea

Introduction: During the COVID pandemic, it was difficult to differentiate COVID diarrhea vs other causes, especially in the HIV/AIDS population. HIV infected patients are at high risk for GI infections. Biopsy of the small intestine identifies etiologies which help to differentiate infection, inflammatory, and neoplastic GI disease. Case Description/Methods: A 39-year-old male presented with two months of epigastric abdominal pain, severe diarrhea, and dehydration during the COVID pandemic in 2020. Past medical history of AIDS wasting syndrome. The patient was severely hypotensive. Exam was notable for mild epigastric tenderness,and hepatomegaly. Complete blood count (CBC) revealed a Hemoglobin (Hg) of 4.3 g. COVID 19 was positive. Gastrointestinal panel PCR was negative. CD4 count 1, HIV RNA viral load 48,700. MRI of the abdomen and pelvis showed diffuse bowel wall thickening in the small intestines. On hospital day 2, Esophagogastroduodenoscopy (EGD) and Colonoscopy were performed for anemia and diarrhea, which revealed abnormal variegated mucosa in the duodenum. Colonoscopy showed a normal mucosal appearance. The pathology report of the duodenum revealed macrophages in the lamina propria, which stained positive for Acid Fast Bacilli. Duodenal biopsy showed markedly expanded lamina propria with numerous histiocytes having finely granular chromatin pattern (Panel 1 and 2). The patient was diagnosed with Mycobacterium avium-intracellulare enteritis. Discussion: This 39-year-old male presented with chronic diarrhea without fever or respiratory symptoms. The most pertinent question for the health care team was whether COVID 19 caused the diarrhea.. Endoscopy with biopsy of the small intestine was essential for an accurate diagnosis. MAC infection in HIV has been dramatically declining since the widespread use of antiretroviral therapy and prophylaxis against MAC infection compared to the 1990s (from 65.3/1000 in 1992 to 2/1000 in 2015) (1). It is important to differentiate MAC from other diseases with a macrophage infiltration or inclusions: including Whipple’s, histoplasmosis, and macroglobulinemia. Patients with MAC enteritis present with fever, and watery diarrhea with diffuse small bowel malabsorption which mimics Whipple’s disease. However, the key to differentiate these two entities is doing a duodenal biopsy showing foamy macrophages with PAS-positive acid-fast bacilli (2).Figure 1.: Histology finding.

Comparison of Cytologic Characteristics between Adenoid Cystic Carcinoma and Adenoid Basal Carcinoma in the Uterine Cervix.

Background:Adenoid cystic carcinoma (ACC) and adenoid basal carcinoma (ABC) are rare in the uterine cervix. ACC is more aggressive than ABC, thus accurate differential diagnosis is important. In this study, we identified cytologic features useful in distinguishing these two tumors for diagnosis.Methods:Three cases of ACC and five cases of ABC were selected for this study. Cervicovaginal smear slides were reviewed retrospectively, and the area, circumference, major axis, and minor axis of nuclei were measured using an image analyzer.Results:ACC displayed three-dimensional clusters with a small acini pattern. ABC displayed peripheral palisading without an acini pattern. The nuclei of ACC were more irregular and angulated than those of ABC, and the former showed a coarsely granular chromatin pattern. The nucleic area, circumference, major axis, and minor axis were 18.556±8.665 µm2, 23.320±11.412 µm, 5.664±1.537 µm, and 4.127±1.107 µm in ACC and 11.017±4.440 µm2, 15.920±5.664 µm, 4.612±1.025 µm, and 3.088±0.762 µm in the cases of ABC. All measured values showed statistically significant difference (p < .001).Conclusions:Although the nuclei of both of these tumor types were oval shaped, inferred from the ratio of minor axis to major axis (0.728 in ACC and 0.669 in ABC), the area of nuclei was approximately 1.7 times larger in ACC than in ABC. Distinguishing nucleic features, including area, morphology, and chromatin pattern, may be helpful in making a correct diagnosis.

Cytologic diagnostic approach to poorly differentiated thyroid carcinoma: a single-institution study.

Fine-needle aspiration cytology (FNAC) is a well-established technique for the preoperative evaluation of thyroid nodules because it is minimally invasive, cost-effective, quick, efficient, and safe. Various articles have discussed differences in the cytomorphology of different types of thyroid cancer. However, review articles on the cytologic diagnosis of poorly differentiated thyroid carcinoma (PDTC) are scarce as PDTC are rare tumors. Although the histologic diagnostic criteria are well standardized, the cytologic diagnostic criteria are not yet standardized. This prompted us to study the cytomorphological features of PDTC and assess features of distinction from differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC). This was a retrospective study of thyroid FNAC smears from 44 PDTC cases retrieved from the database of a single tertiary cancer institute (2009-2013). Papanicolaou and Giemsa smears were evaluated for 21 cytomorphologic features. Immunocytochemistry was available for 6 cases only. The frequencies of cytomorphologic features in the 44 cases were as follows: hypercellularity, 84.1%; insular pattern, 79.5%; small cell size, 93.2%; high nuclear-cytoplasmic ratio, 93.2%; granular chromatin pattern, 95.45%; nuclear overlapping, 88.64%; mild pleomorphism, 86.36%; grooves/inclusions, 22.7%; binucleation/multinucleation, 9.1%; abrupt nucleomegaly, 34.1%; apoptosis, 45%; mitosis, 25%; necrosis, 34.1%; and colloid, 22.7%. A high index of suspicion is necessary for an upfront diagnosis of PDTC on FNAC. Although PDTC, DTC, and MTC have overlapping features, there are distinguishing features also. The cytologic diagnostic criteria for PDTC need to be standardized by collaborative efforts among tertiary cancer centers. A prompt diagnosis is the key feature for planning multimodality treatment.

Basaloid carcinoma of the lung associated with central cavitation: a unique surgical case focusing on cytological and immunohistochemical findings

A history of an increase in pulmonary mass was presented in the right upper lobe of a 72-year-old male. The bronchial brushing cytology specimens contained many sheet-like or three-dimensional clusters of malignant cells having small to medium-sized, uniform oval to round, and hyperchromatic nuclei, inconspicuous nucleoli, and scanty cytoplasm, admixed with mitotic figures. A coarsely granular chromatin pattern was predominantly noted. We first interpreted it as suspicious of malignancy, such as atypical carcinoid. A right upper lobectomy was performed, and gross examination revealed a centrally cavity-formed tumor lesion, containing asymmetrically thinned wall and looking grayish to whitish, partly adjacent to the bronchiolar wall. On microscopic examination, the tumor was predominantly composed of a solid proliferation of atypical epithelial cells without apparent glandular or squamous differentiation, often arranged in an alveolar growth pattern with peripheral palisading. Immunohistochemically, these atypical cells are negative for all three neuroendocrine markers and thyroid transcription factor 1, whereas positive for 34βE12, p63 and S-100 protein. Therefore, we finally made a diagnosis of basaloid carcinoma with cavity formation. We should be aware that, owing to its characteristic features, cytopathologists might be able to raise basaloid carcinoma of the lung as one of differential diagnoses, based on careful cytological examination.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.dianosticpathology.diagnomx.eu/vs/1519986488570234

Clinicopathologic findings in a dog with a retrobulbar meningioma

An 11-year-old Fox Terrier dog was evaluated for a 10-month history of progressive exophthalmia and visual deficits in the right eye. Ophthalmologic examination revealed severe corneal fibrosis and pigmentation, which obscured examination of the anterior chamber of the right eye. There was decreased retropulsion of the right eye. Neurological examination revealed an absent menace response bilaterally. Pupillary light reflex was normal in the left eye. Due to the corneal pathology, pupillary light reflex was unable to be evaluated in the right eye. A retrobulbar mass with heterogeneous echotexture was identified using ultrasonography. Cytological evaluation of a fine-needle aspirate of the mass disclosed a neoplastic cell population consisting of round to polygonal cells with lightly basophilic to gray cytoplasm and round to ovoid nuclei having a coarse granular chromatin pattern. Magnetic resonance imaging disclosed a right-sided retrobulbar mass that extended through the optic canal and was contiguous with an extra-axial mass in the ventral right rostral and middle cranial fossae. The mass displayed homogenous and strong contrast enhancement. Following exenteration, histological examination of the retrobulbar mass was consistent with meningioma. Immunohistochemically, tumor cells stained positive for vimentin (cytoplasmic) and E-cadherin (membranous), and negative for S100, pancytokeratin, and cytokeratins AE1 and AE3.

Characteristic cytological features of histological grade one (G1) breast carcinomas in fine needle aspirates

To analyse the spectrum of nuclear features as well as dissociation pattern found in fine needle aspirates (FNAC) from histological grade 1 breast carcinomas and evaluate the critical cytological features of these lesions. The material consisted of FNAC smears from 494 histologically confirmed grade 1 breast carcinomas. All smears were revaluated for cell dissociation pattern, nuclear size, cell uniformity, nucleoli, nuclear margin and chromatin pattern. All features were compared with the histological subtype and cytological grading. 73.9% of the cases were cytological grade 1, 24.3% were grade 2 and 1.8% were grade 3. The majority of the cases had a cell dissociation pattern showing both a population of single carcinoma cells and cell clusters (65.9%). Practically all tumours had a granular chromatin pattern (94.7%) and a slightly irregular nuclear margin with folds and grooves (94%) irrespective of histological subtype and cytological grading. Nucleoli were mostly indistinct or small (74%), whereas 24.3% were noticeable and 1.7% abnormal. Practically all cases revealed some degree of pleomorphism with 74.3% showing mild and 22.4% a distinct pleomorphism. A small subgroup of IDC was classified as monomorphic (3.3%). Almost all tumours had nuclear sizes in the range of 2-4 x RBC (96.9%). Not all histological grade 1 carcinomas are cytological grade 1. About 25% were grade 2, and a small subpopulation reached grade 3. The typical/average findings in FNAC from grade 1 breast carcinomas were a population of both groups and single cells showing mild pleomorphism, granular chromatin, slightly irregular nuclear margin, indistinct nucleolus and nuclear size 2-4 x RBC.

Cytological study of early cervical adenocarcinoma: special reference to the depth of invasion

Early cervical adenocarcinoma (ECA) with a tumour depth of <3 mm has a good prognosis. To clarify the cytological features of ECAs with depth <3 mm, these were compared with those of ECA with 3-5 mm and invasive adenocarcinoma (IA) invading the cervical wall with more than 5 mm in depth. The cervical cytological features of ECAs with depth <3 mm (14 cases) were compared with those of ECA with 3-5 mm (four cases) and IA (13 cases). Cytologically, the presence or absence of tumour diathesis, number of atypical cells, crowded cell groups, groups with glandular structures, feathering, groups with palisading borders, rosettes, clusters, cell shape and size, nuclear shape and size, nucleolar shape and size, chromatin distribution, border and character of cytoplasm, and single cell pattern were evaluated. A tumour diathesis was seen in five of 14 ECA <3 mm in depth (36%), all four ECA with 3-5 mm (100%) and 11 of 13 IA with more than 5 mm (85%). Single cells, macronucleoli and coarsely granular chromatin pattern were less frequent in ECA of <3 mm than that in ECA with 3-5 mm and IA. The number of atypical cells and glandular structures in ECA was significantly less than that in IA. Cell crowding, feathering, palisading and rosettes were common in both ECA and IA. The characteristic cytological features of ECA with depth <3 mm, having a good prognosis, were clean background, fewer single cells and macronucleoli, and less frequent coarsely granular chromatin pattern compared with those in ECA with 3-5 mm and IA. The number of atypical cells and glandular structures in ECA was significantly less than that in IA. Familiarity with the cytological features of ECA and its mimics is essential.

小細胞癌（神経内分泌癌）を伴った子宮体部異所性癌肉腫の１例

We report a case of uterine corporeal heterologous carcinosarcoma suspected preoperatively of being small cell carcinoma. A 60-year-old woman admitted for abnormal genital bleeding was found in ultarasonography (US) to have an 8×8 cm uterine corporeal tumor and vaginal tumor. Vaginal tumor brushing cytology showed cells had a high N/C ratio and a granular chromatin pattern with ill-difined and crushed nuclei. Histologically, tumor cells proliferated in solid rosette formations and chondrosarcoma was also found. The woman was definitively diagnosed as having uterine corporeal heterologous carcinosarcoma.

Ultrastructural and Immunohistochemical Features of Coronal Adenomas

We studied by electron microscopy three coronal adenomas discovered incidentally in eyes removed surgically. Tumor cells displayed prominent intercellular interdigitations with numerous desmosomes, mitochondria, abundant rough endoplasmic reticulum, and nuclei with membrane infoldings and a granular chromatin pattern. In these characteristics, the tumor cells were identical to nonpigmented ciliary epithelium of the ciliary processes. These growths contained abundant extracellular material, which showed a dimorphic pattern of complex reduplicated basal lamina and granular areas without structure. Immunohistochemical studies on formalin-fixed, paraffin-embedded coronal adenomas demonstrated type IV collagen and laminin in the extracellular material. These findings confirm that coronal adenomas develop from nonpigmented ciliary epithelium and that the extracellular material of these tumors contains components normally present in basement membranes.

Ewing's sarcoma cells in pleural fluid.

A 17-year-old male with effusion in the pleural cavity and a tumor on the left 7th rib was diagnosed by exfoliative cytological and histological examination of pleural fluid and biopsy specimen from the chest wall tumor.In the pleural effusion, small round cells with nuclear atypia were demonstrated as a mixture of monolayered clusters and single cells, with scanty and indistinct cytoplasm. The nucleus was round, supported by thin and smooth nuclear membrane, and hyperchromatic, showing finely granular chromatin pattern with one or two small but distinct nucleoli. PAS stain demonstrated intracellular glycogen. Histologically, biopsy specimen from the chest wall tumor yielded a diagnosis of round cell tumor, compatible with Ewing's sarcoma.Differential diagnosis of small round cell tumors was discussed from a morphological point of view.

Exfoliative Cytopathology of Atypical Pulmonary Carcinoid: A Case Report

A 35-year-old man was diagnosed as having lung cancer and died six years later. In spite of an initial histological diagnosis of squamous cell carcinoma from the biopsy material, the correct diagnosis of atypical carcinoid was made by sputum cytology. The carcinoid cells had exfoliated into the sputum collected immediately after bronchofiberscopic examination although the bronchial tissues obtained at this time did not reveal any histological findings suggestive of neoplasia. The distinctive cytological features in sputum of atypical carcinoid that differentiate it from small cell carcinoma are considered to be the relatively abundant vesicular cytoplasm and the finely reticular or granular chromatin pattern observed in well-preserved tumor cells. The present case also suggests that clinical data may be indispensable to the differential cytological diagnosis of such tumors.

Carcinomas of the lung with neuroendocrine differentiation.

While there are examples of each of the histologic types of bronchogenic carcinoma in which ectopic hormone production has been demonstrated, three groups of lung cancers manifest this type of differentiation with great regularity. These are the carcinoid, atypical carcinoid, and the small cell carcinoma, which have been called neuroendocrine carcinomas of the lung. The carcinoids are neoplasms with a heterogeneous array of histologic appearances that share relatively uniform nuclear features, the absence of both tumor necrosis and mitotic figures, and a good prognosis. Neuroendocrine differentiation is demonstrable with such regularity in carcinoids that the diagnosis is not considered tenable in the absence of at least one of the following features: argyrophilia, the demonstration of neuron-specific-enolase or neuropeptides by immunohistochemistry or other techniques, or the demonstration of numerous dense-core membrane-bound granules, usually 150 to 250 nm in diameter, by electron microscopy. The atypical carcinoids (well or moderately differentiated neuroendocrine carcinomas) share the neuroendocrine differentiation of the carcinoids and many of their histologic features, but are distinguished by the presence of tumor necrosis, more anaplastic large cell nuclei with numerous mitotic figures, and a distinctly worse prognosis. They are a heterogeneous lot with some similarities to carcinoids, small cell carcinomas, and large cell or adenocarcinomas. The demonstration of at least one of the neuroendocrine features listed above is considered necessary for this diagnosis. Small cell carcinoma is also a heterogeneous group of neoplasma primarily distinguished by their finely granular chromatin pattern which correlates with a much worse prognosis but a higher likelihood of response to chemotherapy and radiotherapy. Many small cell carcinomas share the neuroendocrine differentiation of the carcinoids or atypical carcinoids, but some do not and the demonstration of these features is not a requisite for inclusion in the small group. The morphologic demonstration of neuroendocrine differentiation may be more difficult in small cell carcinomas, but they more frequently produce clinically important amounts of ectopic neuropeptides. While the term neuroendocrine carcinoma of the lung includes several quite different entities and does not by itself convey histogenetic or prognostic implications, the demonstration of neuroendocrine differentiation in pulmonary neoplasms is an important procedure when combined with the recognition of other cytologic and histologic features.

Demonstration of normoblasts in tissue sections by means of an immunohistochemical technique for haemoglobin.

The morphological differentiation between normoblasts and lymphocytes in conventionally stained sections of bone marrow trephines may be difficult.' This is unfortunate, especially since the distinction between the two cell types may be quintessential in cases of suspected chronic lymphocytic leukaemia, lymphocytic lymphoma, or other low grade nonHodgkin lymphomas. Guidelines to this problem include the careful observation of nuclear detailfor example, normoblasts have homogenous densely basophilic round nuclei with cytoplasm which shows halo artefact. Conversely, the nuclei of lymphocytes are of a finely granular chromatin pattern and the cells appear to possess no cytoplasm.' None the less, the differences between the cell types are subjective and appearances may be altered by fixation technique. To enable the recognition of normoblasts in paraffin embedded sections of bone marrow trephines we have made use of the peroxidaseantiperoxidase (PAP) method using a primary antiserum against human haemoglobin.t

Morphogenesis of the mouse coronal suture.

The morphogenesis and maturation of the coronal suture in C57Bl-strain mice was studied histologically using light microscopy from day 15 postconception through day 71 postpartum. Early differentiation of the osteoid precursors proceeds centrally within the 7- to 8-cell-thick fibrous ectomeninx beginning in the regions of the ossification centers and extends peripherally toward the future sutural margin. Differentiation into osteogenic cellular elements is marked morphologically by an increased nuclear:cytoplasmic ratio, dark-staining nucleoli and a granular chromatin pattern. This zone of cells, designated the osteogenic induction front (OIF), extends in advance of any identifiable accumulation of osteoid matrix or biomineralization. As the OIFs of the parietal and frontal bones approach, but prior to any physical overlap, they lie in different planes dorsoventrally; the parietal OIF located dorsal to the frontal OIF, a pattern maintained throughout subsequent sutural morphogenesis. Upon physical overlapping of the parietal and frontal OIFs, the fibrous capsule thickens dorsoventrally assuming a 'fusiform' configuration. This morphological event, referred to as the 'fusiform blastema', has been suggested to presage sutural location and determine the relative vertical position of the bony plates comprising the suture. Our results suggest that this is actually a secondary event, the structure of the suture having already been established with the relative physical overlapping of the respective OIFs.

Cytomorphological Characteristics of the Cytotrophoblastic Cells and Their Difference between Noninvasive Mole and Invasive Mole

A total of 2, 600 cytotrophoblastic cells from the molar tissue of 13 cases of non-invasive mole at the implantation site, and 1, 200 cytotrophoblastic cells from the molar tissue of 6 cases of invasive mole in the myometrium were studied cytomorphologically. Variation in size and shape of cytoplasma and nucleus, increased N/C ratio, granular chromatin pattern, multinucleation, and increased number of prominent nucleoli were characteristic of both groups. These characteristic morphologies are common with many other malignant cells in the current sense of cytodiagnosis.The leading papers so far published say that trophoblastic cells of non-invasive mole are easily distinguishable cytologically from those of invasive mole. To the contrary, our results led to the conclusion that the cytomorphological difference of cytotrophoblastic cells between non-invasive mole and invasive mole was rather quantitative than qualitative.Discussion is made on these results in relation to the nature of invasive mole.

Tissue Repair Cells in the Uterine Cervix

The definition of tissue repair cells was proposed. “Tissue repair is a cell group with characteristic features; round or oval in nuclear shape, prominent nucleoli, fine granular chromatin pattern, moderate anisonucleosis and relatively abundant cytoplasm, deriving from reparative tissue. Neoplasia should be ruled out in tissue repair”Cellular origin of tissue repair cells, differential diagnosis between tissue repair cells and cells from neoplasia, and histology from which tissue repair cells were derived were discussed.

Cytologic Diagnosis of Primary Malignant Melanoma of the Vagina

A case of primary malignant melanoma of the vagina diagnosed cytologically was reported. A dark-brownish tumor of fingertip-size was observed, which had developed on the vaginal wall near the introitus of an 87-year-old female.The main cytologic features on vaginal and scraping smears of the tumor were the scattered distribution of atypical cells, anisocytosis, eccentric nuclei with a finely granular chromatin pattern, unusually large red nucleoli, intranuclear vacuoles and finely granular melanin pigment packed in the cytoplasm. No other lesions showing signs of malignant melanoma than the vaginal one could be found anywhere else in the patient's body.A radical vulvectomy with bilateral groin dissection, wide excision of the vagina and external Co60 irradiation for pelvic lymph nodes were carried out. There has been no sign of recurrence during the 6 months following an operation.Cytologic diagnosis of malignant melanoma of the vagina seems to be extremely important in order to avoid its tendency toward hematogenous metastasis.

Cytologic Study of Syncytial Endometritis of Old Woman

1. The case of a forty-nine year old woman, who complained of bloody discharge, was diagnosed as destructive mole by smear tests which exhibited aty pical cytotrophoblasts.Cytologic figures: cytoplasm showed extreme irregu larities in contour and staining reaction.Structural abnormalities of nuclei such as aberrant form, enlargement over 100μ in diameter, coarse granular chromatin pattern were seen.Syncytial endometritis was the pathologic diagnosis by operative specimen.2.The literature on the cytologic findings of cho rionic diseases is reviewed, and the findings of syncyial endometritis discussed.