Small Epithelioid Cells Research Articles

A case report of fungal infection associated acute fibrinous and organizing pneumonitis

BackgroundAcute fibrinous and organizing pneumonitis (AFOP) is an uncommon variant of acute lung injury, characterized by intra-alveolar fibrin and organizing pneumonia. Proposed etiologies include connective tissue diseases, infections, occupational exposure, drug reactions, and autoimmune disease. Here we present a rare case of fungal infection associated AFOP in patient with diabetes mellitus (DM) and review the relevant literature.Case presentationA 67-year-old man complained of cough, fever, dyspnea and hemoptysis. Patient experienced a rapidly progressive course exhibit diffuse predominant consolidation, ground glass opacities, and multifocal parenchymal abnormalities on chest computed tomography (CT). Antibacterial, antifungal, and antiviral treatments were ineffective. A CT-guided percutaneous lung biopsy was performed. Histologically, the predominant findings were as follows: alveolar spaces filled with fibrin and organizing loose connective tissues involving 70% of the observed region, pulmonary interstitial fibrosis, and small abscesses and epithelioid cell granuloma in the focal area. Result of periodic acid-silver methenamine stain was positive. The fungal pathogen from the sputum culture was identified as P. citrinum repeatedly over 3 times. Patient was diagnosed with DM during hospitalization. Corticosteroids combined with an antifungal therapy were effective. Follow-up for 4 months showed complete radiological resolution.ConclusionsAs this common “contaminant” can behave as a pathogen in the immunocompromised host, both clinicians and microbiologists should consider the presence of a serious and potentially fatal fungal infection on isolation of P. citrinum. Based on this case, it could be speculated that AFOP may be associated with fungal infection including P. citrinum.

Primary intraosseous hybrid epithelioid schwannoma/perineurioma in the proximal tibia: a case report of benign hybrid neoplasm with local hypercellularity

BackgroundAs a new entity included in the 4th edition of the WHO classification of tumours of soft tissue and bone in 2013, hybrid peripheral nerve sheath tumours are benign composite neoplasms that demonstrate features of more than one type of nerve sheath tumour, with a wide age distribution and a predilection for superficial location. Those involving deep sites are relatively rare. To the best of our knowledge, only one case of primary intraosseous hybrid peripheral nerve sheath tumours has been documented. In this article, we report another case of hybrid peripheral nerve sheath tumours occurring in bone with different clinical, radiological and pathological features from those in the previously reported cases.Case presentationA 28-year-old female presented with a painful nodule in the right tibia. Radiological examination revealed an oval eccentric osteolytic lesion in the proximal tibia. Histologically, the circumscribed but unencapsulated lesion demonstrated biphasic cellular differentiation. Bland, small epithelioid cells arranged in clusters in the myxoid or collagenous stroma and inconspicuous spindle cells scattered in the hypercellular areas were suggested to originate from Schwann cells according to the detection of S100. Both the elongated spindle cells with thin, wavy nuclei and the spindle cells in fascicular or storiform pattern in hypercellular areas showed a positive immunoreaction for epithelial membrane antigen, indicating perineurial differentiation. Based on histological and immunochemical examinations, the patient was diagnosed with hybrid epithelioid schwannoma/perineurioma. The lesion was resected and has not recurred for 8 months since resection.ConclusionThe present case is the second primary intraosseous hybrid peripheral nerve sheath tumour to be reported. This is also the first reported intraosseous tumour composed of epithelioid schwannoma and perineurioma with hypercellularity, indicating diverse involvement sites and a wide range of histological features among hybrid peripheral nerve sheath tumours. Awareness of such diversity is critical for accurate diagnoses. The morphological overlap with other spindle and epithelioid cell neoplasms, especially pure peripheral nerve sheath tumours, requires that immunochemical and molecular examinations be used as objective tools to provide the necessary information for a differential diagnosis.

AB045. Prognostic significance and characterization of small epithelioid cell population in uveal melanoma

AB045. Prognostic significance and characterization of small epithelioid cell population in uveal melanoma

Endoscopic Ultrasound-Guided Fine Needle Biopsy for the Diagnosis of Paraganglioma

Paragangliomas are rare neuroendocrine tumors that originate from the extra-adrenal autonomic ganglia. They should be included in the differential diagnosis of retroperitoneal tumors. Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) has been increasingly used as an effective tool for obtaining diagnostic tissue for histology and molecular studies. We are reporting a patient who was found to have a retroperitoneal mass as an incidental finding and was successfully diagnosed as a non-functional paraganglioma using EUS-FNB without any complications. 50-years-old man who presented to the emergency department after a high-speed motorcycle accident; Computed tomography showed large retroperitoneal mass measuring 9.6 x 12.5 cm. It was a peripherally enhancing, centrally necrotic mass that abuts the Inferior vena cava and aorta. EUS-FNB showed an epitheliod lesion composed of medium sized cells with moderate eosinophilic to clear cytoplasm. Immunostains showed the tumor cells to be positive for CD56 and synaptophysin but negative for pancytokeratins AE1/3 and CAM5.2, Pax-8, CK7, inhibin, S-100 and CD117. This indicates neuroendocrine differentiation, consistent with paraganglioma. He tolerated the procedure well without any complications. Biochemical studies were consistent with non-functioning extra adrenal paraganglioma. The following month, he underwent successful surgical resection of the mass. Paragangliomas can be found in different sites, with the majority being found in the abdomen. They could be either functioning or non-functioning. The functional ones secrete norepinephrine and normetanephrine and represent 36% to 60% of the lesions. Less than 10% could turn malignant. EUS-FNB allows preoperative diagnosis of such lesions. In patients with clinical signs of pheochromocytoma, it is advisable to do 24-hour urine collection of catecholamines and metanephrines before performing EUS-FNB as it is contraindicated in functioning paragangliomas as needle insertion could trigger an adrenergic crisis. In conclusion, EUS-FNB is a safe technique for evaluation of retroperitoneal masses. Physicians should consider biochemical testing to exclude functioning paraganglioma in patients with retroperitoneal masses who have clinical signs of pheochromocytoma prior to performing EUS-FNB to avoid intra-procedural complications.Figure: Abdominal CT (upper left) shows large retroperitoneal peripherally enhancing centrally necrotic mass that measures 9.6 x 12.5 X 10.7 cm. EUS (upper right) shows the mass with the needle going through for fine needle aspiration. FNA cytology slide (bottom left) stained with H&E stain shows small epithelioid cells with moderate pleomorphism, and fine salt and pepper chromatin similar to that seen in neuroendocrine tumors. The paraganglioma mass (bottom right) is shown after surgical resection.

MiT family translocation renal cell carcinoma.

The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs.

A clinicopathologic and immunohistochemical study of 7 cases of sclerosing perineurioma.

Sclerosing perineurioma is a relatively rare tumor that has remained widely unknown since first reported by Fetsch in 1997. To our knowledge, no large or small series of claudin-1 in sclerosing perineurioma has been confirmed to date. We collected 7 new cases of sclerosing perineurioma. Six patients were female, and 1 was male. The patients' age ranged from 15 to 58 years (mean, 36.6 years; median, 42.0 years). The primary reason for consultation at the outpatient clinics was a slowly enlarging mass. The preoperative durations were available for 4 of the 7 cases and ranged from 2 to 7 years. Six tumors were located in the fingers, and the other tumor was found in the palm. The sizes ranged from 4 to 12 mm in diameter (mean, 6.7 mm; median, 6.0 mm). Microscopically, all tumors were nodular lesions, with sclerotic stroma involving reticular dermis primarily consisting of small oval epithelioid cells and plump spindle cells, scattered and arranged in corded, trabecular, reticular, and/or whorled growth patterns. The neoplastic cells were immunoreactive for epithelial membrane antigen (7 of 7) and glucose transporter 1 (7 of 7). The periodic acid-Schiff reaction and positive immunostaining for type IV collagen were observed directly adjacent to the lesional cells in all cases (6 of 6). Claudin-1 immunostaining was positive in all 7 cases, suggesting that claudin-1 may serve as a helpful diagnostic marker for sclerosing perineurioma.

Re-characterization of established human retinoblastoma cell lines.

Retinoblastoma (RB) is the most common malignant intraocular childhood tumor. Forty years after their first description, in the present study, we re-characterized seven established retinoblastoma cell lines with regard to their RB1 mutation status, morphology, growth pattern, endogenous apoptosis levels, colony formation efficiency in soft agar and invasiveness and dissemination capacity in chick chorioallantoic membrane (CAM) assays. All RB cell lines predominantly resemble small epithelioid cells with little cytoplasm and large nucleus, which mainly grow in cell clusters, but sometimes form chain-like structures with incident loops or three-dimensional aggregates. We observed different growth rates for the different retinoblastoma cells investigated. RBL-30, RBL-13 and RBL 383 cells grew very slowly, whereas Y-79 cells grew fastest under our culture conditions. Apoptosis rates likewise differed with highest cell death levels in RB 383 and RB 355 and lowest in WERI-Rb1 and RBL-15. Contradicting former reports, six of the seven RB cell lines analyzed were able to form colonies in soft agarose after single cell seeding within 3 weeks of incubation. Upon inoculation of four out of seven RB cell lines on the dorsal CAM, GFP-positive cells were detectable in the ventral CAM and two RB cell lines caused tumor development, indicating their intravasation and dissemination potential. All RB cell lines exhibited the potential to extravasate from the capillary system after intravenous CAM injection. Our study provides valuable new details for future therapy-related retinoblastoma basic research in vitro.

Cellular mesenchymal tumors of the uterus: a review emphasizing recent observations.

Cellular mesenchymal tumors of the uterus may be divided in 2 main groups, smooth muscle and endometrial stromal. Among the former, highly cellular leiomyoma is the classic example. This tumor is not infrequently confused with an endometrial stromal tumor due to its often yellow color and soft consistency, dense cellularity, striking vascularity, not uncommon irregular margin and even rarely association with seedling cellular leiomyomas, both mimicking the infiltration of a low-grade endometrial stromal sarcoma. Cellular intravenous leiomyomatosis can also mimic endometrial stromal sarcoma due to their shared intravascular growth. A variety of histologic features typical of cellular smooth muscle including clefts and differing vasculature help in this distinction. Although endometrial stromal tumors are typically highly cellular, recent studies have expanded their spectrum to include those that are less so due to smooth muscle metaplasia, fibrous and myxoid change, and even oxyphilic cytoplasm. A subset now designated high-grade endometrial stromal sarcoma showing a t(10;17) has been characterized to show small epithelioid cells associated with brisk miotic activity, typically being CD10, ER and PR negative, and cyclin D1 positive. These tumors are juxtaposed to areas of fibromyxoid endometrial stromal neoplasia in 50% of cases. An enigmatic category of uterine mesenchymal neoplasms, often densely cellular, are those descriptively referred to as "uterine tumors resembling ovarian sex cord tumors." Their spectrum is briefly noted as is their crucial distinction from stromal sarcoma with sex cord-like differentiation. Other tumors that rarely occur in the uterus that are densely cellular include but are not limited to undifferentiated uterine sarcoma, embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, lymphoma or small cell, or undifferentiated carcinoma. In this essay, I review the most helpful morphologic, immunohistochemical, and/or cytogenetic features in the diagnosis of each one of these entities.

Granulomatous Pancreatitis in a Patient with Acute Manifested Insulin-Dependent Diabetes Mellitus

Isolated granulomatous noncaseating pancreatitis is a rare condition exceptionally described in human population. We demonstrate a case of the a 71-years-old female patient suffering from recent diabetes mellitus, generalized atherosclerosis and hypertension who died due to pulmonary embolism and terminal bronchopneumonia. Lipomatosis of pancreatic tissue was observed during the postmortem examination. Histological examination of pancreatic tissue discovered multiple small noncaseating epithelioid cell and giant cell granulomas, partly replacing the islets of Langerhans. To our knowledge, our case represents the first description of noninfectious granulomatous pancreatitis associated with acute manifested insulin-dependent diabetes mellitus.

Epithelioid Cell Granulomatous Response of Waldeyer's Ring among Japanese : A Clinicopathological and Immunohistochemical Study of 16 Cases

The tonsils are uncommonly affected by granulomatous inflammation. This study attempted to clarify the clinicopathological and immunohistochemical findings and presence or absence of Epstein-Barr virus (EBV) in tonsilar granulomatous inflammation. A total of 537 consecutive specimens from tonsillectomies performed at Dokkyo University School of Medicine between 1999 and March 2012 were reexamined. Using formalin-fixed, paraffin-embedded sections, histological, immunohistochemical, and in situ hybridization (ISH) studies were performed. Epithelioid granulomas (EPGs) were identified in the tonsils in 16 (3.0%) cases. There were 8 males and 8 females, aged 4 to 57 years (mean, 23). In 11 patients, EPGs were located in the germinal center (GC), whereas they were located in the interfollicular area as well as GC in the remaining 5 cases. Three types of EPG have been delineated : (i) poorly demarcated small epithelioid cell granulomas (n = 6) ; (ii) well-demarcated non-caseating sarcoid-like granulomas (n = 5) ; and (iii) EPGs within GC showing suppurations at the center (n = 5). An ISH study demonstrated EBV-encoded small RNA (EBER)(+) cells in 4 lesions. The present study demonstrated that the majority of EPGs were located in the GC and tonsilar EPGs showed histological variation.

Clinicopathological features of Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly

To investigate the clinicopathological features of EB virus positive diffuse large B-cell lymphomas (EBV + DLBCL) of the elderly. Four hundred and ninety-six cases of DLBCLs were retrospectively studied by in situ hybridization (ISH) to detect the EBV in tumor cells, and by immunohistochemistry to evaluate the expression of CD10, CD20, CD30, CD79a, bcl-6, bcl-2, MUM-1, CD5, CD3, TIA-1 and Ki-67 protein. Their clinicopathological correlations were analyzed. Of the 59 cases of EBV + DLBCL, 48 cases were EBV positive. The median age of these EBV + DLBCLs was 73 years with male predominance (1.4:1). There were 11 cases with nodal presentation only, 18 cases with extra-nodal presentation and 19 cases with both lymph nodal and extra-nodal involvements, whereas about one third cases with more than one extra-nodal involvement. Thirty-five patients presented with advanced disease (Ann Arbor stage III/IV). A performance status was available in 36 cases and 5 cases had performance status of more than 1. Seven of 30 patients were found with high lactate dehydrogenase value (more than twice of the normal). An IPI-score was calculated in 30 cases and 18 cases had an intermediate/high IPI-score (3-5). The median survival for these patients was 35 months. Morphologically, EBV + DLBCLs of the elderly generally showed a diffuse and polymorphic proliferation of large lymphoid cells with varying degrees of reactive components including small lymphocytes, plasma cells, histiocytes, and epithelioid cells. These tumor cells were frequently characterized by a broad range of B-cell maturation, containing centroblasts, immunoblasts, and Hodgkin- and Reed-Sternberg (HRS)-like giant cells. The study cohort was further morphologically divided into large cell lymphoma subtypes (n = 33) and polymorphic lymphoma subtypes (n = 14) and one case with mixed subtype. Immunohistochemical studies showed that tumor cells were positive for CD20 (47/48) and/or CD79a (45/45) in almost cases. Tumor cells were MUM-1-positive in the majority of the cases (44/47) and were stained for CD10 or bcl-6 in a few cases. Expression of bcl-2 and CD30 was observed in 80.0% (28/35) and 28.9% (11/38) cases, respectively, and most of the cases (33/39) had a high proliferative index (by Ki-67 with a 50% cut-off point). Compared with other EBV + DLBCLs, except the older age and low frequency of bcl-6 staining, no other significant differences were observed in EBV + DLBCLs of the elderly. EBV + DLBCLs of the elderly constitute a distinct clinicopathologic subtype of DLBCL, although many clinical and histological features with EBV + lymphomas are similar with that of younger ages. Differential diagnosis from other types of lymphomas should also be considered.

Mucosal Benign Epithelioid Nerve Sheath Tumors

Mucosal nerve sheath tumors have been well described in the gastrointestinal tract and other mucosal sites. In a series of mucosal biopsies, we have encountered a distinct subset of mucosal peripheral nerve sheath tumors characterized by small epithelioid cells and a benign clinical course. Such epithelioid nerve sheath tumors have been observed as a component of a larger study of colorectal "schwannomas," but herein we describe them in detail. A series of 7 of these lesions detected on mucosal biopsies (6 colonic, 1 bladder) was received by a single large institution in consultation material. The histologic and clinicopathologic features of the cases were reviewed. The mean age at presentation was 58.6 years with a slight female predominance (4 females, 3 males). Five of the colonic lesions were from the left colon and one from the right colon. The bladder biopsy was from the bladder neck. All of the colonic lesions were discovered as small (0.2-1.0 cm) polyps during the time of colonoscopy (3 at the time of routine screening, 2 for the workup of occult blood in the stool). The bladder neck mass was seen on bladder ultrasound after the patient presented with vaginal bleeding. None of the patients had a known history of neurofibromatosis. Histologically, the lesions showed an infiltrative growth pattern and were composed of spindled to predominantly epithelioid cells arranged in nests and whorls. The epicenters of the lesions were located in the lamina propria and extended to the superficial submucosa. The proliferating cells had uniform round to oval nuclei with frequent intranuclear pseudoinclusions and eosinophilic fibrillary cytoplasm. No mitoses were seen. All lesions expressed diffuse S-100 protein, and 3 of 5 lesions stained showed CD34 labeling in supporting cells. All were negative for CD117. All 5 lesions tested were negative for calretenin, while SM31 showed no intralesional neuraxons. One lesion was stained for epithelial membrane antigen and was negative. One lesion was associated with superficial mucosal erosion, and 1 had an inflammatory infiltrate predominantly composed of eosinophils. On follow-up of 5 patients, none has had any symptoms or recurrence of disease. Mucosal epithelioid nerve sheath tumors are a rare entity characterized by prominent epithelioid round to oval cells with an infiltrative growth pattern. These lesions are often discovered incidentally and have a benign clinical course.

Persistent unilateral orbital and eyelid oedema as a manifestation of Melkersson–Rosenthal syndrome

Melkersson-Rosenthal syndrome (MRS) is a complex neuromucocutaneous disorder characterized by localized orofacial oedema and cranial nerve dysfunction, frequently associated with minor signs, including furrowed tongue. Complete forms are rare whereas mono- and oligosymptomatic variants are more common. A 71-year-old man presented with a 2-year history of relapsing and progressively persistent oedema of the right eyelids and periorbital region. A fissured tongue and telangiectatic rosacea had been present since the age of 50 and 60 years, respectively. The patient was also affected by essential hypertension and diabetes mellitus. A skin biopsy showed a marked upper dermal oedema, and small epithelioid cell granulomas arranged in perivascular and perilymphatic location. Collections of small epithelioid cells were occasionally observed within lymphatic spaces. No acid-fast bacteria, fungi or foreign bodies were detected. Intralesional corticosteroids induced transient improvement, whereas minocycline, clofazimine and dapsone have been ineffective. MRS may present with unilateral eyelid and periorbital swelling. Differential diagnoses of such cases may include a variety of cutaneous, ophthalmic and systemic diseases.

Perineurioma: a clinicopathological study of eight cases

Perineuriomas (PN) are uncommon, benign neoplasms that mimic a number of benign and malignant soft tissue lesions. There are two main forms: a rare intraneural PN (IPN), and a relatively more common extraneural soft tissue PN (STPN) including a conventional form (STPNc), sclerosing (SPN), reticular and lipomatous variants. Their diagnosis requires immunohistochemical (IHC) and/or ultrastructural (US) confirmation of perineurial cell differentiation. This study aims to review the clinicopathological features of eight PN we encountered recently, to raise awareness of PN as an entity and to highlight the differential diagnoses which include potentially aggressive lesions. Clinical, histological, IHC and US features of seven STPN and one IPN were studied. The eight PN arose in the limbs of six females and two males aged 30-58 years. Five STPN occurred in subcutis, one intramuscularly and one intradermally. The STPN were well-circumscribed, multinodular growths. STPNc contained bland spindle cells with long cytoplasmic processes arranged in lamellae, storiform patterns and whorls. Three SPN were acrally located and additionally contained small epithelioid cells in cords and clusters in a myxohyaline stroma with extensive sclerosis. One SPN had giant collagen rosettes of spiral collagen. The IPN showed 'pseudo-onion bulbs' of perineurial cells. All PN were at least focally EMA positive, six of eight were Claudin-1 positive and all were S100 protein negative. Common US features were organelle-poor cell processes, many pinocytotic vesicles, sparse intermediate filaments, and tight junctions and patchy external lamina. There were no recurrences (follow-up 1-49 months). PN has a variable morphology and can mimic many benign, borderline and malignant lesions, the differential diagnoses of which are discussed. When confronted with a subcutaneous (in particular) spindle and/or epithelioid cell lesion, EMA/Claudin-1 stains and/or US are essential to identify PN and thereby avoid inappropriately aggressive therapy.

Differentiation of the corpus luteum of the mink (Mustela vison): mitogenic and steroidogenic potential of luteal cells from embryonic diapause and postimplantation gestation.

The mink corpus luteum (CL) involutes after ovulation and remains dormant, synthesizing low amounts of progesterone until reactivated to terminate embryonic diapause. We examined the mitotic and steroid synthetic capacity of luteal cells from the diapause and postimplantation phases of mink gestation. Cells from diapause divided in vitro, reaching confluence in 7-8 days. Three phenotypes were distinguishable: a fusiform cell in whorls, a hypertrophied epithelioid cell, and a small epithelioid cell. The first and second cell types divided in vitro after confluence, evidenced by localization of proliferating cell nuclear antigen (PCNA) in their nuclei. The small epithelioid cells were present in cell nests and showed no PCNA activity. Cells derived from reactivated CL did not reach confluence and had no PCNA activity. Progesterone accumulation was enhanced in luteal cells from diapause by LH, FSH, and dibutyryl (Bu2)cAMP, and by LH and (Bu2)cAMP in cells from reactivated CL. In luteal cells from the diapause phase of gestation, LH and (Bu2)cAMP induced increases in mRNA coding for steroidogenic acute regulatory protein, while cytochrome P450 side-chain cleavage enzyme mRNA was increased by prolactin, LH and (Bu2)cAMP. Cellular concentrations of 3beta-hydroxysteroid dehydrogenase-delta5-4-isomerase mRNA were increased by prolactin and (Bu2)cAMP. Thus, luteinization in the mink CL does not engender exit from the cell cycle, as both fusiform and hypertrophied cells from diapause divide in vitro. Reactivation appears to represent terminal differentiation. LH is capable of stimulating steroidogenesis in vitro in luteal cells from diapause, and prolactin and LH appear to have both specific and overlapping stimulatory effects on the CL of this species.

Acquired homozygosity (isodisomy) of chromosome 3 during clonal evolution of a uveal melanoma: Association with morphologic heterogeneity

Cytogenetic investigation of untreated uveal melanoma has shown that the most frequent abnormality is monosomy 3, which occurs in approximately 60% of cases. One of our cases showed distinct pigmented and nonpigmented areas at gross dissection; representative tissue was collected separately from each area, cultured, and harvested using standard cytogenetic techniques. On histologic examination, the pigmented area was found to be composed of small epithelioid cells, whereas the nonpigmented area contained large, pleomorphic epithelioid cells. The karyotype of the pigmented tumor revealed monosomy 3, whereas the nonpigmented tumor showed two apparently normal chromosomes 3. Our purpose in the present study was to investigate the two tumor areas by molecular techniques to determine whether the karyotype of the nonpigmented tumor evolved directly from the pigmented tumor with duplication of the remaining chromosome 3 or whether the two sublines evolved in a divergent fashion from a common precursor stemline. DNA was extracted from normal lymphocytes and separately from both areas of the tumor. The DNA was analyzed using the polymerase chain reaction for polymorphic dinucleotide and tetranucleotide repeat sequences on chromosome 3. Both pigmented and nonpigmented areas of the tumor showed loss of heterozygosity at all informative loci on chromosome 3 that were tested. These results support our hypothesis that an abnormality on chromosome 3 plays a central role in the molecular pathogenesis of uveal melanoma and that some melanomas develop acquired homozygosity (isodisomy) by loss and duplication of the remaining, presumably abnormal, chromosome 3.

Low-grade B-cell lymphomas of the splenic marginal zone: a clinicopathological and immunohistochemical study of 14 cases.

We have studied 14 cases of low-grade, splenic marginal zone, B-cell non-Hodgkin's lymphoma. The clinical presentation in all cases was with splenomegaly and, in 10 cases, circulating neoplastic lymphoid cells in the peripheral blood with involvement of bone marrow. In all cases the splenic white pulp was hyperplastic with expansion of marginal zones and varying degrees of infiltration of germinal centres by neoplastic cells. The cells were a mixture of medium sized lymphocytes with moderate amounts of cytoplasm and finely dispersed nuclear chromatin, together with occasional blast cells with small nucleoli. Satellite red pulp aggregates of tumour cells centred on small epithelioid cell clusters were seen in all cases. These appear to be a characteristic and diagnostically important feature of splenic marginal zone lymphoma. The tumour cells expressed CD20, CD45RA, bcl-2 and the antigens detected by MB2. All cases expressed IgM with light chain restriction. In addition, IgD was expressed in four cases. The follicular dendritic cell network was disrupted in those follicles which were infiltrated by tumour cells. A network of stromal myoid cells, at the periphery of the marginal zone, identified by expression of alpha-smooth muscle actin, was preserved. Alpha-smooth muscle actin positive dendritic cells were also seen within and around satellite tumour nodules in the red pulp.

Differential alpha‐smooth muscle actin expression in a gastric epithelioid leiomyosarcoma in a 14 year old girl

Leiomyosarcoma in childhood is very rare. This report describes the immunohistochemical study of a gastric epithelioid leiomyosarcoma in a 14 year old girl. Microscopically, the tumor showed two distinct histological patterns within the same tumor: small epithelioid cells forming a lobular pattern and spindle-shaped cells forming interlacing fascicles, but no distinct border divided the two types of cells. Immunohistochemically, vimentin was positive in all tumor cells; alpha-smooth muscle actin, however, was negative in small epithelioid cells and positive in spindle-shaped cells. The data revealed that the tumor had components showing two stages of morphological and biochemical differentiation. This case indicates that leiomyosarcomas might lose smooth muscle actin during malignant transformation; or, alternatively, they might arise from a primitive type of smooth muscle cell and some of them could spontaneously differentiate into mature smooth muscle cells, expressing this actin.

Characterization of fibroblast clones from periodontal granulation tissue in vitro.

Connective tissues are known to be composed of heterogeneous fibroblast subpopulations. The significance of this heterogeneity in different physiological and pathological conditions is poorly understood. Granulation tissue is formed in connective tissue during wound healing, chronic inflammation, and certain pathological conditions. In this study, heterogeneity of fibroblasts from granulation tissue was investigated by cell-cloning techniques. Granulation-tissue fibroblasts (GTFs) from both chronically inflamed periodontal lesions and healing wound granulation tissue behaved similarly. GTFs showed a more pronounced decrease in proliferative capacity with increasing cumulative population doubling levels (CPDLs) and 30-40% lower cloning efficiency compared with normal gingival fibroblasts (HGFs). Morphologically, cells in GTF cultures were mainly large, whereas HGFs were mainly small in size. Both cell-line types showed heterogeneity in cell morphology. Clones composed of large stellate-like cells predominated in GTF cultures, whereas clones composed of small spindle-shaped or epithelioid cells predominated in HGF cultures. In both cell-line type the proportion of clones composed of large cells increased without increasing CPDL. These findings show that the properties of the fibroblasts changed during their in vitro life spans. The finding that normal connective tissue and granulation tissues contain morphologically distinct fibroblast clones in different proportions suggests that local factors could stimulate local fibroblasts to differentiate into GTFs. Alternatively, local factors could select some fibroblast subpopulations to overgrow the others to form granulation tissue.

The spectrum of minimal deviation melanoma: A clinicopathologic study of 21 cases

A retrospective study of 21 patients with the histopathologic diagnosis of minimal deviation melanoma (MDM; n = 18) and borderline melanoma (BM; n = 3) was undertaken to determine the prognosis for these patients compared with that for patients with other types of malignant melanoma. The findings indicate that the prognosis for these uncommon nevomelanocytic tumors is somewhat better than that for other malignant melanomas. Follow-up periods in this series ranged from 18 to 96 months (mean, 57 months). Primary lesions ranged in thickness from 1.6 to 10.4 mm. The histopathologic subtypes included the Spitz variant (nine patients), the spindle cell variant (six patients), the combined spindle and epithelioid cell type (three patients), and the small epithelioid cell type (three patients). Only two of the patients died of widespread metastatic disease. Comparison of the histologic and clinical prognostic indicators of mortality in patients who have malignant melanoma with the clinical and pathologic features seen in this series of 21 patients would appear to indicate a diminished tendency toward metastatic or recurrent disease in patients with MDM and BM.