Abundant Mitotic Activity Research Articles

S3139 Primary Hepatic Diffuse Large B Cell Lymphoma Presenting as a Picture of Acute Alcoholic Hepatitis

Introduction: Diffuse large B cell lymphoma (DLBCL) is a prevalent subcategory of Non-Hodgkin lymphoma (NHL) comprising around 25% of all NHL occurrences. Generally, 60% of cases will present with Stage III/IV advanced disease vs 40% with localized disease. While DLBCL can arise from any tissue, 40% of cases will come from extranodal extramedullary tissue; most commonly the stomach or GI. Interestingly, primary hepatic lymphoma is exceedingly rare with a reported incidence of 0.4% of all extranodal NHL and 0.016% for all NHL. The presentation can be vague and a mimicker of other disease with symptoms such as abdominal pain, bloating, nausea, vomiting, and B symptoms. Case Description/Methods: A 59-year-old female with no significant medical history presented for dizziness, fatigue, fever, shortness of breath, weight loss, night sweats, chills × 1 month. She drinks 18 beers/week and is employed at a bar. Initially found to have thrombocytopenia, transaminitis (AST > ALT), hepatosplenomegaly, hypotension, normocytic anemia, latent hepatitis B, and a pulmonary embolism. Her hepatitis was thought to be secondary to alcoholic hepatitis. Her MELD was 12 and Maddrey of -0.6. GI was consulted, further workup showed a past EBV and CMV infection. Quantiferon, HIV, mono, autoimmune and rheumatologic workup were negative. Ultimately a liver biopsy was positive for DLBCL. She was vaccinated for encapsulated organisms, treated for her Hepatitis B, and initiated on R-EPOCH regimen. She was transitioned to RCHOP and ultimately had no evidence of FDG presence on PET Scan and complete response to therapy. She was advised to have routine surveillance per NCCN guidelines (Figure 1). Discussion: Primary hepatic DLBCL is rare and not often diagnosed when a patient presents with acute hepatitis and known risk factors of alcohol use. However, our patient had multiple B-symptoms concerning for lymphoma. The only way to definitively diagnose DLBCL is by liver biopsy with the prevailing management of EPOCH chemotherapy. Early diagnosis and initiation of treatment is crucial due to its poor prognosis and advanced stage presentation. For this reason, a broad differential diagnosis must be considered when evaluating patients with alcoholic hepatitis. This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.Figure 1.: A, Markedly atypical lymphoid infiltrate involving both the hepatic sinusoids and portal tracts. The lymphocytes are large with vesicular chromatin, prominent nucleoli, and fairly abundant mitotic activity B, Immunohistochemical stains are performed. The atypical lymphocytes react with CD20, PAX5, and coexpress BCL-2 (90%) and C-MYC (60%).

1943 Gastrointestinal Plasmacytomas

INTRODUCTION: Plasmacytomas are tumors consist of abnormal plasma cells.They are divided into solitary plasmacytomas of the bone and extramedullary plasmacytomas (EMP). GI tract involvement is seen in 7% of EMP cases. The small intestine is the most commonly involved GI site, followed by stomach, colon, and esophagus. CASE DESCRIPTION/METHODS: A 57-year-old African American female with a history of multiple myeloma treated with chemotherapy followed by autologous stem cell transplant with failure to achieve remission. She presented with a two day history of melena, hematochezia and fatigue. Vital signs: BP 85/45 mmHg, HR 98 bpm, T 98.6 F, RR 18, Oxygen sat 96% on RA. Labs showed a drop in hemoglobin from 8.4 g/dL to 4.9 g/dL. Upper endoscopy showed 1.5 cm polyp in the gastric body (Figure 1a) that was removed. Colonoscopy showed multiple colonic polyps with a 1.5 cm polyp (Figure 1b) in the ascending colon that was removed. Histopathologic examination of stomach polyp (Figure 2a,d) revealed a malignant neoplasm consisting of plasmacytoid cells with inconspicuous nucleoli and abundant mitotic activity. The neoplastic cells were directly infiltrating the residual gastric epithelium and extending beyond the muscularis mucosa. Immunohistochemical staining showed the cells to be strongly positive for CD138 and lambda light chain, while negative for CD20, CD3, and Kappa light chain. These findings were consistent with a diagnosis of plasmacytoma. Histopathologic examination of the colon polyp (Figure 2e,f) showed similar morphology to the gastric polyp. DISCUSSION: Gastrointestinal plasmacytomas are rare, accounting for approximately 7% of all EMPs. Endoscopically, GI plasmacytomas have variable morphological appearances including ulcers, polyposis, thickened folds, ulcerative masses, and constricting lesions. Differentiating GI plasmacytomas from other tumors require histopathological examination. GI plasmacytomas should be considered in the differential diagnosis of myeloma patients presenting with GI bleed.

Ectopic Cortisol and Androgen-Producing Adrenocortical Carcinoma Arising from Adrenal Rest Tissue in a Kidney: Case Report and Literature Review

ABSTRACT Objective: To present a case of an aggressive adrenocortical carcinoma producing both ectopic cortisol and androgens and to provide an extensive literature review of similar cases. Methods: A case presentation is provided that illustrates clinical, biochemical, radiologic, and pathologic findings. We also conducted a PubMed search for similar cases and summarize 15 other cases of malignant adrenal rest tissue. Results: A 50-year-old woman presented with symptoms of Cushing syndrome and virilization. Urine free cortisol and serum adrenal androgens were significantly elevated. Computed tomography of the abdomen revealed a 12-cm mass within the right kidney. Subsequently, the patient underwent right radical nephro-adrenalectomy. The tumor showed a high-grade neoplasm centered in the kidney with polymorphism, highly atypical nuclei, abundant mitotic activity, and necrosis. The Ki-67 proliferation index was 25 to 30%. Immunohistochemical staining of the neoplastic cells favored an adrenal origin. The ...

Retinal histogenesis in an altricial avian species, the zebra finch (Taeniopygia guttata, Vieillot 1817).

Comparative developmental studies have shown that the retina of altricial fish and mammals is incompletely developed at birth, and that, during the first days of life, maturation proceeds rapidly. In contrast, precocial fish and mammals are born with fully differentiated retinas. Concerning birds, knowledge about retinal development is generally restricted to a single order of precocial birds, Galliformes, due to the fact that both the chicken and the Japanese quail are considered model systems. However, comparison of embryonic pre-hatchling retinal development between altricial and precocial birds has been poorly explored. The purpose of this study was to examine the morphogenesis and histogenesis of the retina in the altricial zebra finch (Taeniopygia guttata, Vieillot 1817) and compare the results with those from previous studies in the precocial chicken. Several maturational features (morphogenesis of the optic vesicle and optic cup, appearance of the first differentiated neurons, the period in which the non-apical cell divisions are observable, and the emergence of the plexiform layers) were found to occur at later stages in the zebra finch than in the chicken. At hatching, the retina of T.guttata showed the typical cytoarchitecture of the mature tissue, although features of immaturity were still observable, such as a ganglion cell layer containing many thick cells, very thin plexiform layers, and poorly developed photoreceptors. Moreover, abundant mitotic activity was detected in the entire retina, even in the regions where the layering was complete. The circumferential marginal zone was very prominent and showed abundant mitotic activity. The partially undifferentiated stage of maturation at hatching makes the T.guttata retina an appropriate model with which to study avian postnatal retinal neurogenesis.

A Histologic and Immunohistochemical Study Describing the Diversity of Tumors Classified as Sinonasal High-grade Nonintestinal Adenocarcinomas

Nonintestinal sinonasal adenocarcinomas (SNACs) are somewhat poorly characterized and high-grade nonintestinal SNACs have been only rarely reported. Here, we review our experience with these tumors. Twenty-seven cases of high-grade nonintestinal SNACs were identified from 22 men and 5 women. Ages ranged from 22 to 83 years (mean±1 standard deviation=54.7±18.6 y; median=60 y). Thirteen cases involved the nasal cavity and sinuses, 10 involved the nasal cavity only, and 4 involved sinuses only. Most cases had marked cytologic and nuclear pleomorphism, abundant mitotic activity, and necrosis; however, these features were not uniform. Although histologically heterogeneous, recurrent growth patterns were seen that resembled other neoplasms of the area. Tumors lacked CDX2 and CK20 immunoreactivity (aside from rare CK20 immunoreactive cells). High-grade nonintestinal SNACs are more common in men and, although they occur over a wide age range, they are much more common in older individuals. Histologically, they show a great deal of heterogeneity.

Low-grade Mucinous Adenocarcinoma of the Uterine Corpus

Uterine corpus mucinous epithelial proliferations present diagnostic challenges due to histologic similarities to cervical lesions. We present a rare but distinctive endocervical-like mucinous carcinoma of the uterine corpus resembling adenoma malignum of the cervix that can be mistaken for a benign endometrial process. The clinical-pathologic features of 16 endometrial carcinomas exhibiting a pure endocervical-like mucinous proliferation were evaluated. Hysterectomy and available prehysterectomy specimens were assessed for architectural complexity, nuclear pleomorphism, macronucleoli, nuclear pseudostratification, mitotic index, necrosis, prominent neutrophils, and voluminous extracellular mucin (mucin encompassing >50% of a ×40 field). Cases involving the cervix or lower uterine segment were confirmed as endometrial in origin based on immunohistochemical stains (estrogen receptor, progesterone receptor, p16, and vimentin). Patient age ranged from 45 to 70 years; 6 of 16 (38%) were premenopausal, 11 of 16 (69%) had abnormal bleeding, and 7 of 16 (44%) had a history of hormonal therapy. Prehysterectomy diagnoses were benign in 2 of 16 (13%) cases, borderline in 9 of 16 (56%) cases, and carcinoma in 5 of 16 (31%) cases, whereas 8 of 16 (50%) hysterectomy specimens showed myoinvasive adenocarcinoma. With the exception of 2 cases, architectural complexity was low-to-moderate and no specimens showed marked nuclear pleomorphism. Macronucleoli and abundant mitotic activity were absent. Nuclear pseudostratification was present in 7 of 16 (44%) cases, necrosis in 1 of 16 (6%) cases, prominent neutrophils in 7 of 16 (44%) cases, and voluminous extracellular mucin in 9 of 16 (56%) cases. Cytologically bland mucinous epithelial proliferations should be diagnosed with caution in endometrial samplings. The presence of an endocervical-like mucinous epithelial process in association with voluminous extracellular mucin should prompt consideration for a low-grade mucinous adenocarcinoma of the uterine corpus.

Intracardiac Mass in a Man Infected With Human Immunodeficiency Virus

Intracardiac Mass in a Man Infected With Human Immunodeficiency Virus

Knee Pain in a 13-Year-Old Boy

Knee Pain in a 13-Year-Old Boy

P63 Coordinates Anogenital Modeling and Epithelial Cell Differentiation in the Developing Female Urogenital Tract

p63 is a p53 homologue required for cutaneous development that is expressed in immature squamous epithelium and reserve cells of the cervix. Humans with p63 mutations exhibit defects in limb, accessory organ (skin appendage, breast, prostate), and genitourinary development. Because p63 expression patterns imply a strong role of the gene in the female genital tract development, newborn female p63-/-, +/-, and +/+ mice were examined in situ, dissected, and compared. Nuclear p63 protein was localized to the skin, vagina, bladder, urethra, and basal columnar cells of the caudal uterus in p63+/+ and +/- animals. p63-/- mice exhibited abnormal genital morphogenesis with hypoplastic genitalia, a single cloacal opening, and persistence of columnar epithelium at lower genital tract sites that normally undergo squamous and urothelial differentiation. The defects observed support p63-dependent pathways of genital tract development that permit externally, ectodermal basal cell replenishment integral to reciprocal epithelial stromal signaling, urorectal septation, and modeling of the external genitalia; and internally, the emergence of basal epithelial cell populations capable of divergent epithelial cell differentiation in the vagina, cervix, and urinary tract. Defects in the first pathway explain imperforate anus, vaginal septum, genital hypoplasia, and micropenis reported in humans with p63 mutations. The second is necessary for the generation of multipotential reserve cells in the cervix and may be operative in other epithelial stromal interactions integral to the emergence of uterine basal cells later in life.

Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors.

Endometrial stromal tumors are divided into three types: benign stromal nodules, endometrial stromal sarcomas, and undifferentiated endometrial sarcomas. A variety of cytogenetic abnormalities involving chromosome 7 have been reported in endometrial stromal sarcomas, including a recurrent t(7;17)(p15;q21). We have identified two zinc finger genes, which we have termed JAZF1 and JJAZ1, at the sites of the 7p15 and 17q21 breakpoints. Analyses of tumor RNA indicate that a JAZF1/JJAZ1 fusion is present in all types of endometrial stromal tumors; however, the fusion appears to be rarer among endometrial stromal sarcomas that would be considered high-grade according to certain classification schemes. These findings suggest that the less malignant endometrial stromal tumors may evolve toward more malignant types, but that some endometrial stromal sarcomas with relatively abundant mitotic activity may compose a biologically distinct group.

Degeneration patterns of postganglionic fibers following sympathectomy.

In cats the time course of degeneration following lumbal sympathectomy was studied in the ramus communicans griseus (rcg) and in the nerves to the triceps surae muscle using light and electron microscopic methods. The left lumbar sympathetic trunk including its rami communicantes was removed from L2 to S1 using a lateral approach. The animals were sacrificed between 2 and 48 days after the sympathectomy. Tissue samples were taken (a) one cm proximal to the entrance of the rcg into the spinal nerve, and (b) one cm proximal to the entrance of the nerve into the muscle belly. In the rcg signs of degeneration can already be recognized in the myelinated as well as in the unmyelinated axons 48 h after sympathectomy. The degenerative processes in the axons reach their peak activity at about 4 days p.o. They end a week later. Signs of the reactions of the Schwann cells and of the endoneural cells can first be seen 2 days p.o. They are most pronounced around the 8th day p.o., and last at least up to the third week. Thereafter the cicatrization processes settled to a rather steady state (total observation period 7 weeks). In the muscle nerves the first signs of an axonal degeneration of the sympathetic fibers can be recognized 4 days after surgery. The signs of axonal degeneration are most striking about 8 days p.o. They have more or less disappeared another week later. The reactions of the Schwann cells also start on the fourth day but outlast the degenerative processes by some 8 days. Thus the degenerative and reactive processes in the rcg precede those in the muscle nerves by 2 days early after surgery and by 6 days 3 weeks later. Seven weeks after surgery, fragments of folded basement lamella and Remak bundles with condensed cytoplasm and numerous flat processes are persisting signs of the degeneration. In addition to the differences in time course between the proximal and the distal site of observation, it was also noted that both the axonal degeneration and the reactions of the Schwann cells are more pronounced in the rcg than in the muscle nerve. For example there was abundant mitotic activity in the central endoneural and Schwann cells whereas we could not detect such activity in the periphery.(ABSTRACT TRUNCATED AT 400 WORDS)

Merkel cell carcinoma of the skin: the structure and origin of normal Merkel cells.

A series of 15 Merkel cell tumours of skin is reported. They occur dominantly on the head and neck and on the extremities of elderly women, frequently presenting as a reddish nodule. Three cases were associated with squamous carcinoma at the same site, an association deserving further study. There are two main patterns: the commoner one takes the form of a trabecular carcinoma in the dermis mimicking metastatic carcinoma, including oat-cell carcinoma and neuroblastoma: a dissociated-cell form mimicks malignant lymphoma. The triad of vesicular nuclei with very small nucleoli, abundant mitotic activity and apoptosis is so characteristic as to be virtually pathognomonic in conjunction with structural features. Argyrophilia is common, but Bouin fixation is necessary to demonstrate it regularly. Small round secretory granules (89 +/- 18 nm) with narrow haloes, and an abundance of intermediate size filaments are among the ultrastructural hallmarks. There is a close similarity between better differentiated tumour cells and normal Merkel cells. The neural crest origin of MC is in doubt both on the basis of studies of the development and regeneration of MC and from the study of Merkel cell tumours.

GRISEOFULVIN THERAPY AS A CAUSE OF LYMPH NODE PROLIFERATION RESEMBLING MALIGNANT HISTIOCYTOSIS

The relationship between lymphadenopathy and certain drugs especially the hydantoins has been well documented. Although the histologic appearance of the lymph node may be quite disturbing and suggest a malignant lymphoma, most cases, but not all, are clinically and pathologically benign. This report documents the occurrence of a lymph node proliferation in a child which resembled malignant histiocytosis. The differential diagnostic problem between malignant histiocytosis and immunoblastic lymphadenopathy in childhood is illustrated and explored in the context of this case.A 12-year-old male developed a generalized rash, fever, diffuse lymphadenopathy (including mediastinal) and hepatosplenomegaly soon after the onset of Griseofulvin therapy. An enlarged cervical lymph node revealed a predominatly sinusoidal proliferation of large, atypical “histiocytoid” cells and abundant mitotic activity. Partial obliteration of the follicular architecture had occurred. Following an interpretation of probable malignant histiocytosis, Griseofulvin therapy was discontinued and it was elected to withhold further treatment. All abnormal clinical findings regressed and the patient has remained well for over 2 years. A repeat lymph node biopsy was unremarkable. Retrospectively, the atypical “histiocytoid” cells represented, in fact, “immunoblasts” or transformed lymphocytes and the process more appropriately belongs to the category of immunoblastic lymphadenopathy (N. Engl. J. Med,292: 1,1975. Am J Med 59:803, 1975).

Sarcoma-like disease in a single specimen of the American oyster.

AbstractAn unusual lesion observed in the right mantle of an oyster, Crassostrea virginica [see Couch: Nat. Cancer Inst. Monogr. 31: 557–562, 1969], resembles certain reticulum sarcomas of mammals. Characteristics shared by the oyster tumor and mammalian reticulosarcoma are: (1) relatively large blastoid (anaplastic?) cells with scant cytoplasm and enlarged, pleomorphic nuclei; (2) occasional binucleate or multinucleate cells; (3) many mitoses (many more than found in comparable normal or injured tissue); (4) focal (tumor-like condition) rather than diffuse distribution of blastoid cells; and (5) altered patterns of reticulum fibers.Further histological and cytological study of this tumor, utilizing Lillie’s stain for reticulum and the mercury bromophenol blue method of Mazia, Brewer and Alfert for total protein, reveals that alterations in the connective tissue stroma result from invasion and replacement of normal vesicular connective tissue cells by large blastoid cells. These stromatic alterations are of two forms: (1) collapse and aggregation of remnants of normal reticulum fibers upon replacement or degeneration of normal vesicular cells; and (2) apparent (though, perhaps, not real) increase in reticulum in limited areas of the tumor as compared to normal areas in other oysters. The blastoid cells have a marked affinity for the total protein stain in cytoplasm and nuclei and show a much more intense staining for protein than do normal hemocytes, vesicular cells, and epithelial cells.Additionally, abundant mitotic activity suggests that active protein synthesis is a biochemical characteristic of oyster blastoid cells and supports the hypothesis that these are largely undifferentiated or anaplastic, neoplastic cells. It is recognized that active protein biosynthesis is a characteristic of normal cells undergoing division or elaborating secretory substances. However, the intensely proteinaceous nature of these cells is related to their neoplastic character since this oyster tumor and its unusual blastoid cells are highly abnormal and rare (1/5,000 oysters examined). The Alcian blue method for acid mucopolysaccharides showed no increase in acid mucopolysaccharides in the tumorous mantle epithelium, or in the lesion proper. No recognizable parasites or infectious agents were found in the oyster sections studied.The origin of the blastoid cell remains enigmatic. Additional specimens with this rare conditions are essential for further study.