Search

The most common malignancy of the esophagus is squamous cell carcinoma (SCC) and regional lymph node metastases are an important prognostic factor. Isolated tumor cells (ITCs) are defined as single tumor cells or small clusters of tumor cells not exceeding 0.2 mm. The prognostic role of ITCs is not clear. This study aimed to determine the prevalence of ITCs in regional lymph nodes in patients with esophageal SCC and to investigate how frequently ITCs represent part of a true metastasis. Surgical specimens from 100 patients with SCC of the esophagus were included. All original H&E stained slides containing lymph nodes were reviewed by two gastrointestinal pathologists. In lymph nodes containing ITCs, additional levels were cut and stained with a H&E- and a cytokeratin stain. Areas of tumor cells that measured >0.2 mm on the deeper sections were classified as metastases. A total of 2460 lymph nodes were examined. ITCs were detected in 10 lymph nodes (0.4%) from nine patients (9%). Deeper sections revealed metastases in five out of the 10 lymph nodes (50%). ITCs in regional lymph nodes of patients with SCC of the esophagus is a rare finding compared with patients with adenocarcinoma of the esophagogastric junction. However, deeper sections often revealed metastases. Therefore, in patients with SCC of the esophagus, we recommend additional sectioning and immunohistochemical examination of lymph nodes when ITCs are detected on the first slide., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

SW480 and SW620 colon carcinoma cell lines derive from primary tumour and lymph-node metastasis of the same patient, respectively. For this reason, these cells represent an ideal system to analyse phenotypic variations associated with the metastatic process. In this study we analysed SW480 and SW620 cytoskeleton remodelling by measuring the cells' mechanics and morphological properties using different microscopic techniques. We observed that different specialized functions of cells, i.e. the capacity to metastasize of elongated cells inside the primary tumour and the ability to intravasate and resist shear forces of the stream of cells derived from lymph node metastasis, are reflected in their mechanical properties. We demonstrated that, together with stiffness and adhesion between the AFM tip and the cell surface, cell shape, actin organization and surface roughness are strictly related and are finely modulated by colorectal cancer cells to better accomplish their specific tasks in cancer growth and invasion.

The aim of this study was to compare the efficacy of physical examination (PE), ultrasound (US), and US combined with fine-needle cytology (US-FNAC) in evaluation of node status before sentinel lymph node biopsy (SLNB) for breast cancer patients. We performed a retrospective study of 3,781 breast cancer patients and calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for PE, US, and US-FNAC, respectively. A total of 3,175 cases were documented as cN0 and 606 as cN1. Abnormal axillary nodes under US were detected in 1,152 cases, among which 821 were proven to have positive nodes by FNAC. The positive FNAC results enabled 11.7% of cN0 patients (373/3,175) to avoid unnecessary SLNB. All 331 cases with abnormal US but negative FNAC results, and the 2,629 cases with normal US underwent SLNB procedure for nodal staging, and metastatic nodes were identified in 745 patients. The sensitivity of PE was 32.2%, with a specificity of 95.5%, a PPV of 83.5%, a NPV of 65%, and an accuracy of 69.3%. The sensitivity, specificity, PPV, NPV, and accuracy of axillary US alone were 58.6, 89.4, 79.6, 75.3, and 76.7%, respectively. Combining axillary US with FNAC resulted in sensitivity, specificity, PPV, NPV, and accuracy of 52.4, 100, 100, 74.8, and 80.3%, respectively. Our study demonstrated that US-FNAC is a feasible and effective triage during axillary staging for newly diagnosed breast cancer patients.

Background: Ultrasound and prophylactic dissections have facilitated identification of small-volume cervical lymph node (LN) metastases in patients with papillary thyroid carcinoma (PTC). Since most staging systems do not stratify risk based on size or number of LN metastases, even a single-microscopic LN metastasis can upstage a patient with low-risk papillary thyroid microcarcinoma (PMC) to an intermediate risk of recurrence in the American Thyroid Association (ATA) system and to an increased risk of death in the American Joint Committee on Cancer (AJCC) staging system (stage III if the metastatic node is in the central neck or stage IVA if the microscopic LN metastasis is identified in the lateral neck). Such microscopic upstaging may lead to potentially unnecessary or additional treatments and follow-up studies. The goal of this review is to determine if the literature supports the concept that specific characteristics (clinically apparent size, number, and extranodal extension) of LN metastases can be used to stratify the risk of recurrence in PTC., Summary: In patients with pathological proven cervical LN metastases (pathological N1 disease; pN1), the median risk of loco-regional LN recurrence varies markedly by clinical staging, with recurrence rates for patients who are initially clinically N0 (clinical N0 disease; cN0) of 2% (range 0%-9%) versus rates of recurrence for patients who are initially clinically N-positive (clinical N1 disease; cN1) of 22% (range 10%-42%). Furthermore, the median risk of recurrence in pN1 patients varies markedly by the number of positive nodes, <5 nodes (4%, range 3%-8%) vs. >5 nodes (19%, range 7%-21%). Additionally, the presence of extranodal extension was associated with a median risk of recurrence of 24% (range 15%-32%) and possibly a worse disease-specific survival., Conclusion: Our previous paradigm assigned the same magnitude of risk for all patients with N1 disease. However, small-volume subclinical microscopic N1 disease clearly conveys a much smaller risk of recurrence than large-volume, macroscopic clinically apparent loco-regional metastases. Armed with this information, clinicians will be better able to tailor initial treatment and follow-up recommendations. Implications of N1 stratification for PTC into small-volume microscopic disease versus clinically apparent macroscopic disease importantly relate to issues of prophylactic neck dissection utility, need for pathologic nodal size description, and suggest potential modifications to the AJCC TNM (tumor, nodal disease, and distant metastasis) and ATA risk recurrence staging systems.

Micropapillary carcinoma of the bladder is an extremely aggressive variant of urothelial carcinoma. Radical cystectomy is the standard treatment for all patients, including those with nonmuscle-invasive disease. We present a patient diagnosed with clinical Stage T1 micropapillary carcinoma of the bladder who was found to have a 2-cm metastasis to the head of the pancreas. To our knowledge, this case represents the first report of a solitary metastatic urothelial carcinoma to the pancreas., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A 3.5-year-old intact male double-transgenic New Zealand white rabbit (Oryctolagus cuniculus), apoA-I and LCAT (apolipoprotein and lecithin:cholesterol acyltransferase), was presented with a discrete, raised facial mass (0.5 x 1.0 x 1.0 cm). The mass was surgically excised, with reoccurrence to the same site 88 days later. A second surgical excision was performed, and the rabbit died 3 weeks later from respiratory distress. At necropsy, multiple varying-sized masses were observed in the ventral mandibular region and throughout the lungs, pleura, and diaphragm. On histopathology, the masses were composed of moderately anisocytotic and anisokaryotic polygonal to spindloid cells with moderate finely granular, lightly eosinophilic cytoplasm, having round to oval nuclei with one to several nucleoli and finely stippled chromatin. Mitotic figures were frequent. Lymphatic and venous invasion were noted with neoplastic cells metastasized to the submandibular lymph nodes, lungs, liver, and adventitial surface of the aorta. Fontana-Masson stain was negative for melanin, thereby necessitating immunohistochemistry and transmission electron microscopy. Positive staining with MART-1 (a melanocyte protein marker) combined with transmission electron microscopy revealing type II melanosomes confirmed the diagnosis of an amelanotic melanoma.

Aim: The lymphatic distribution of magnetic carbon nanotubes was studied in vivo and compared with magnetic-activated carbon particles, which were selectively taken up in the lymphatic channels and delivered to the regional lymph nodes., Material & Methods: Magnetic multiwalled carbon nanotubes functionalized with poly(acrylic acid) (mMWNTs) and magnetic-activated carbon particles were subcutaneously injected in mice. The draining lymph nodes were harvested at different times postadministration to examine the lymphatic distribution of these particles. The short-term accumulation and toxicity of mMWNTs in the major organs were studied., Results: mMWNTs had the same properties of lymph node mapping as magnetic-activated carbon particles in mice independent of lymph node metastasis. The degree of black staining of lymph nodes and concentration of mMWNTs had a dose-response relationship. Aggregation of magnetic particles was found around the metastatic foci within the lymph nodes. Footpad injection of mMWNTs did not cause any obvious local or systemic toxicities, and no particle agglomerates were found in the major organs., Conclusion: The feasibility of targeting magnetic carbon nanotubes to lymph nodes was demonstrated and the results support further studies for their potential use in diagnosing and treating cancer.

Objective: To assess the characteristics of enhanced magnetic resonance image with ultrasmall superparamagnetic iron oxide (USPIO) in the inflammatory and tumor metastatic rabbit model, and explore its relevance with histologic ultrastructural findings., Methods: Totally 36 New Zealand white rabbits were randomly divided into lymphadenitis group and metastatic group. Complete Freund's adjuvant was injected into the bilateral dorsal footpads of 18 rabbits to set up ipsilateral lymphadenitis model. The other 18 rabbits received a subcutaneous implantation of VX2 tumor cell suspension (1.5 x 10(7) cells/ml) in both thighs to set up metastatic lymph node model. Magnetic resonance scan were performed 24 hours before and after USPIO (90 micromol Fe/kg) injection. T2 values of each lymph node were measured and lymph node T2 enhancement rate was calculated as well. HE staining, Prussian blue staining, and electronic microscopy were performed to observe the pathological microstructure changes and the distribution of the iron particle in lymph node. Relationship between lymph nodes USPIO enhancement and its microstructures were further analyzed. Results Thirty-six lymph nodes in lymphadenitis group showed different degrees of reactive hyperplasia. Twenty-six lymph nodes in metastatic group were invaded by tumor cell. Non-enhanced scan showed mild difference between T2 signal intensity of the two pathological lymph node types. After USPIO enhancement, inflammatory lymph nodes showed distinct T2 signal reduction at the center, and metastatic lymph nodes showed homogenous and faint T2 signal reduction. Enhancement rate of benign and malignant lymph nodes were 57.39% and 29.45% respectively (P < 0.01). HE staining and Prussian blue staining indicated USPIO particles located mainly in the macrophages at inflammatory lymphatic medulla, while paracortical area and cortical area contained relatively much less USPIO particles due to less macrophages distribution. MRI findings were correlated with the pathological results. Electronic microscopy also verified that the majority of USPIO particles were located in the numerous cytophagic bubbles of macrophages. Lymph nodes metastasis including 4 lymph nodes with completed structure destruction due to entire tumor infiltration, 19 lymph nodes with partially lymph node structure destruction but reduced USPIO-contained macrophage numbers or reduced USPIO particles in macrophages, and 3 lymph nodes with only localized foci tumor metastasis at subcapsular area. Conclusions USPIO enhancement pattern of different lymph nodes is closely related to distribution and functional status of the intra-node macrophages. It may affect the accuracy of the lymph node property diagnosis based on USPIO enhanced image.

Lymphoma diagnosis rarely needs electron microscopy (EM), but one area where it can be useful is in the distinction of cytokeratin-positive lymphoma from carcinoma. The authors describe such a case, where difficulties were encountered due to lack of antibody specificity, distinguishing reactive from tumoral cells, and suboptimal sampling for EM. The tumor was in a lymph node next to the right submandibular gland in a 69-year-old man. This was a malignant tumor, composed of sheets of monomorphic large round cells. Interpretation on the part of a team of pathologists who examined this tumor was divided. On histological sections, the differential diagnosis was between carcinoma and lymphoma, which was modified to cytokeratin-positive lymphoma versus carcinoma since tumor cells were found to be cytokeratin-positive. EM of tumor retrieved from formalin showed plasmablastic features, in keeping with lymphoma with plasmablastic differentiation, one of the light microscopy diagnoses. The moderately strong positivity of cytokeratin and the positivity for Ber-EP4, however, supported carcinoma, and further sampling for EM was carried out, specifically on a cytokeratin-positive area of the wax block. Tonofibrils were found, supporting carcinoma. The final diagnosis was undifferentiated carcinoma with unknown primary site. The study emphasizes the need to take into account the imperfect specificity of cytokeratin, which can be found in several hemolymphoid neoplasms, to distinguish reactive from neoplastic cells, and to secure appropriate sampling for EM. This is one of the occasions where dewaxing (of an immunohistochemically defined wax block) offers positive advantages, despite compromised structural preservation, in the search for diagnostically important organelles.

Sentinel lymph node (SLN) biopsy affords an accurate, minimally invasive means of staging and determining prognosis in patients with melanoma and for identifying those patients who may benefit from complete regional lymph node dissection. Careful and accurate histopathologic assessment of SLNs is critical to achieving optimal reliability of the technique. Micromorphometric parameters of melanoma deposits in SLNs have been shown to be predictive of regional non-SLN involvement and of clinical outcomes. Several non-histopathologic methods of SLN evaluation have been investigated, and while some of them show promise for the future, excision and histopathologic examination currently remains the gold standard for the evaluation of SLNs.

Accurate lymph node staging in genitourinary malignancy is an important component in the diagnostic algorithm and therapeutic planning. A promising new method for lymph node staging is lymphotrophic nanoparticle enhanced magnetic resonance imaging. This novel technique uses ultrasmall superparamagnetic iron oxide particles, which localize in lymph nodes and provide detailed characterization of these nodes independent of typically accepted size criteria. This review provides a brief overview of the presently accepted methods for noninvasive lymph node staging and thoroughly discusses lymphotrophic nanoparticle enhanced MR imaging: a technique that can be used for accurate detection of lymph node metastases and will likely play a major role in noninvasive lymph node staging in genitourinary cancer in the near future.

The distribution and fine structure of the tumor-associated absorbing lymphatic vessel in the tumor mass of prostate adenocarcinoma and of seminal vesicle metastasis in transgenic mice was studied for the purpose of understanding the modality of tumor cell transendothelial passage from the extravasal matrix into the lymphatic vessel. In the tumor mass, two main cell populations were identified: stromal tumor cells and the invasive phenotype tumor (IPT) cells, having characteristics such as a highly electron-dense matrix rich in small granules lacking a dense core and massed nuclear chromatin, which is positive to immunostaining with anti-SV40 large T antigen antibody. Based on the ultrastructural pictures of different moments of the IPT cell transendothelial passage by ultrathin serial sections of the tumor-associated absorbing lymphatic vessel, the manner of its transendothelial passage through the intraendothelial channel, without involving intercellular contacts, was demonstrated. The presence of IPT cells in the parenchyma of satellite lymph node highlights its significant role in metastatic diffusion. The intraendothelial channel is the reply to the lack of knowledge regarding the intravasation of the tumor cell into the lymphatic circulation. The lymphatic endothelium would organize this channel on the basis of tumor cell-endothelial cell-extravasal matrix molecular interactions, which are as yet unidentified.

Aim: To document the clinical, histological, immunohistochemical and ultrastructural features of three malignant melanomas showing neuroendocrine differentiation., Methods and Results: Three patients, two with primary cutaneous melanoma and one with nasal mucosal melanoma, subsequently developing or simultaneously presenting with metastatic malignant melanoma, were studied by conventional histological technique, immunohistochemistry of formalin-fixed paraffin-wax embedded tissues, and electron microscopy of epoxy-resin-embedded tumour tissue. Tumours showed either small cell or conventional malignant melanoma cell morphology. One of the three primary melanocytic lesions (the nasal melanoma) exhibited neuroendocrine differentiation immunohistochemically. All three metastatic malignant melanomas showed, in varying combinations, immunohistochemical and ultrastructural evidence for neuroendocrine differentiation: they were positive for the melanocytic markers, S100 protein, HMB-45, Melan-A and tyrosinase, and the neuroendocrine markers chromogranin, synaptophysin and neurofilament protein. Ultrastructural study in two of the metastases revealed neuroendocrine granules but no lattice-bearing melanosomes., Conclusions: The cases described are the most comprehensively investigated malignant melanomas showing neuroendocrine differentiation to date, and the first to document neuroendocrine differentiation ultrastructurally in these tumours. Malignant melanoma with neuroendocrine differentiation therefore needs to be recognized among the other, better known variants of malignant melanoma.

A case of metastatic malignant melanoma exhibiting small cell morphology is described. The patient had had a previous primary nodular small cell melanoma. The metastatic tumor was examined by conventional histology, light microscope immunohistochemistry, conventional electron microscopy, and ultrastructural immunolabeling. It consisted of small cells, which, however, varied in size and were present in distinct but merging areas. Tumor cells were negative for S-100 protein and very focally positive for cytokeratin: these findings in combination with small cell morphology suggested the possibility of small cell carcinoma. However, other melanocytic markers were positive. Neuroendocrine markers were negative. By electron microscopy, tumor cells lacked unambiguous melanosomes but contained paranuclear aggregates of nondescript granules. Following ultrastructural immunolabeling, these were found to be decorated with gold-labeled HMB-45 antibodies, thereby confirming them as lattice-deficient melanosomes. This tumor is an uncommon example of malignant melanoma where immunoultrastructural analysis helped clarify the nature of otherwise nondescript granules as true but lattice-deficient melanosomes. This is also the first case of small cell melanoma to be studied by electron microscopy.

We describe a case of primary pulmonary paraganglioma, a tumor that has not been reported in sufficient detail in previous literature. The patient was a 55-year-old woman with hypertension accompanied by an elevated serum norepinephrine level (2651 pg/mL; normal 100-450 pg/mL). Computed tomography revealed a well-circumscribed solid mass, 3.5 cm in diameter, located in the lower lobe of the left lung. In the lobectomy specimen, the tumor had invaded the B8 bronchus and hilar lymph nodes with microscopic metastasis to the mediastinal nodes. The tumor showed histologic, immunohistochemical, and ultrastructural features of paraganglioma: argyrophilic cells arranged in a nesting (Zellballen) or anastomosing trabecular pattern within an arcuate vascular network. Neoplastic chief cells positive for neuroendocrine markers (CD56, synaptophysin, chromogranin A) were surrounded by sustentacular cells positive for S-100 protein. Neurofilament protein was positively stained, but cytokeratins were totally negative. On electron microscopy, chief cells possessed abundant dense core granules with an eccentric halo ("norepinephrine-type" granules). The patient's blood pressure began to decline soon after the resection, and her serum norepinephrine promptly returned to almost normal. On the basis of our experience, our case is a bona fide primary pulmonary paraganglioma, a tumor heretofore subject to considerable skepticism.

A 56-year-old woman presented with a right inguinal mass. Biopsy revealed multiple lymph nodes involved with papillary and gland-like structures extending into the surrounding fibroadipose tissue. There was no history of carcinoma or other malignancy. Ultrastructural findings included long microvilli, desmosomes, and tonofilament bundles, indicating metastatic malignant mesothelioma. Malignant mesothelioma only rarely presents as a lymph node metastasis, and electron microscopy is very useful in establishing this diagnosis.

Background: Although there is a significant understanding of the vascular anatomy of the upper aerodigestive tract (UADT), there is less detailed knowledge of the architecture and drainage patterns of the lymphatic system. Detailed knowledge of the lymphatic system is critical for understanding the role of sentinal node identification in the management of different cancers., Methods: We have combined microscopic techniques with in vivo and in vitro lymphographic studies to survey the architecture and drainage patterns of the lymphatic system of the UADT in 850 organ specimens., Results: These studies show an interaction of superficial and deep lymphatic networks that vary in density but have a constant distribution characterized by predictable patterns of lymph drainage into the regional lymph nodes., Conclusions: Detailed knowledge of the lymphatic system of the UADT contributes to a better understanding of the patterns of metastatic spread of carcinomas of the UADT and provides a strong rationale for the practice of sentinel node identification in the management of these tumors., (Copyright 2003 Wiley Periodicals, Inc.)

The morphological presentation of malignant plasma cells in multiple myeloma (MM) varies from mature to anaplastic plasma cells with only one reported case of signet ring variant. We describe here another case of signet ring-like lambda light chain MM associated with extra-skeletal spread to lymph nodes, spleen and liver. The clinical and pathological presentations were atypical with no evidence of bone-lytic lesions or monoclonal component on protein electrophoresis, leading to a delay of several years in the diagnosis. Recognition of this morphological entity of MM may help in an early diagnosis of this rare variant.

Purpose: The aim of this study was to determine why colorectal tumors confined to submucosa rarely metastasize. Under normal conditions, the submucosa contains many large lymphatic vessels with thin walls that would presumably favor the spread of cancer cells through the lymphatic system., Methods: Specimens of colorectal cancer tissue, the border between tumor and normal tissue, and normal tissue were obtained from patients undergoing radical resection of colorectal cancer. The material was embedded in methacrylate resin for light microscopy and Epon for transmission electron microscopy examination. Light microscopy observations were routinely performed on serial sections., Results: No lymphatic vessels were ever found in the tumor mass. The border area contained peritumoral inflammatory infiltrate of variable thickness. Where submucosal lymphatic vessels came into contact with peritumoral inflammatory infiltrate, they were profoundly altered: their endothelium was fragmented, and their walls were disrupted. These altered lymphatic vessels were almost always accompanied by mast cells, which were observed in the process of degranulating toward the lymphatic endothelium. No such alterations were detected in blood vessels., Conclusion: Our results suggest that mast cells, probably influenced by inflammatory infiltrate and/or colorectal cancer cells, destroy lymphatic vessels, which prevents cancer cells from spreading through the lymphatic system.

The aim of this study was to compare the clinical usefulness of ultrasmall superparamagnetic iron oxide (USPIO) MR contrast media (Sinerem, Guerbet Laboratories, Aulnay-sous-Bois, France) with precontrast MRI in the diagnosis of metastatic lymph nodes in patients with head and neck squamous cell carcinoma, using histology as gold standard. Eighty-one previously untreated patients were enrolled in a multicenter phase-III clinical trial. All patients had a noncontrast MR, a Sinerem MR, and surgery within a period of 15 days. The MR exams were analyzed both on site and by two independent radiologists (centralized readers). Correlation between histology and imaging was done per lymph node groups, and per individual lymph nodes when the short axis was > or = 10 mm. For individual lymph nodes, Sinerem MR showed a high sensitivity (> or = 88%) and specificity (> or = 77%). For lymph node groups, the sensitivity was > or = 59% and specificity > or = 81%. False-positive results were partially due to inflammatory nodes; false-negative results from the presence of undetected micrometastases. Errors of interpretation were also related to motion and/or susceptibility artifacts and problems of zone assignment. Sinerem MR had a negative predictive value (NPV) > or = 90% and a positive predictive value (PPV) > or = 51%. The specificity and PPV of Sinerem MR were better than those of precontrast MR. Precontrast MR showed an unexpectedly high sensitivity and NPV which were not increased with Sinerem MR. The potential contribution of Sinerem MR still remains limited by technical problems regarding motion and susceptibility artifacts and spatial resolution. It is also noteworthy that logistical problems, which could reduce the practical value of Sinerem MR, will be minimized in the future since Sinerem MR alone performed as good as the combination of precontrast and Sinerem MR.

This work demonstrates differences between B lymphocytes and T lymphocytes as seen in the scanning electron microscope (SEM). Slides of routinely prepared benign and malignant lymphoid tissues were viewed in the SEM. The location of prominent populations of T lymphocytes and B lymphocytes was verified by immunocytochemical staining respectively with CD3 and CD20 antisera. Benign tissues, including infant thymus and adult hyperplastic lymph node, were compared with malignant lymphomas of T-cell and B-cell types. The SEM appearance of benign B and T lymphocytes is compared utilizing the backscattered electron (BSE) mode and secondary electron (SE) mode in adult hyperplastic lymph node and infant thymus, respectively. The BSE and SE modes reveal that the sectioned T-lymphocyte nucleus has a more complex configuration than that of the B lymphocyte. T lymphocytes appear more discrete and separated one from another, while B lymphocytes exhibit close cellular association to form a syncytial array. These features are noted also in malignant lymphomas of B-lymphocyte and T-lymphocyte types, respectively. The SEM can distinguish between B and T lymphocytes by studying the differences in nuclear and chiefly the cell to cell appearances. The syncytial configuration of B lymphocytes may reflect prominent expression of cell adhesion molecules, e.g., ICAM-1, as noted in the literature.

Since epithelial inclusions in axillary lymph nodes are rare, some diagnostic problems concerning their nature have arisen. We report a case of a cystic squamous epithelial inclusion in an axillary lymph node of a patient affected by a high grade breast carcinoma with focal squamous differentiation. Although the lesion was histologically benign, the possibility that it represents a well-differentiated squamous metastasis cannot be completely ruled out. To our knowledge, this is the first case of an epithelial lymph node inclusion associated with a breast carcinoma showing morphological evidence of squamous differentiation. Here, we discuss the diagnostic problems and give a review of the literature.

Nuclear grooves have been described as a cytologic feature in a variety of extrathyroid lesions. When a cytologic specimen demonstrates prominent longitudinal nuclear grooving, a wide range of pathologic lesions should be considered. To our knowledge, the two cases presented are the first report of longitudinal nuclear grooving described in cytologic preparations of malignant melanoma.

The ultrastructural modes of lymphatic and blood vessel invasions were studied comparatively in hamsters with squamous cell carcinoma (O-1N) that had a high potential for lymph node metastasis. The endothelial injury, which was caused by mechanical stretching with the growth of O-1N, was the initial and characteristic feature common to both vascular invasions. Tumor cell nests penetrating the lymphatic lumen through disrupted endothelial cells still maintained their volume and continuity to the underlying tumor cell nests. In contrast, pronounced microthrombotic and neutrophilic reactions occurred at the site of blood vessel penetration. Within the lymphatic lumen, large clusters of O-1N cells were kept longer in spite of lymphocytic and macrophagic reactions. In blood vessels, clusters of tumor cells that had passed through dense fibrin layers were reduced in size and further disintegrated into smaller pieces by neutrophils. In conclusion, lymphatic invasion is a mechanical process, and smooth and direct invasion of large tumor cell nests into lymphatic vessels is responsible for causing more prompt and frequent lymph node metastasis in O-1N than a hematogenous type.

A case history of a patient showing signs of upper gastrointestinal bleeding is described. Extensive analysis showed that the bleeding was due to a malignant Schwannoma of the stomach with several lymph node metastases. The patient was operated on and is doing well 5 years after surgery. The literature on this rare malignant tumour is reviewed.

Background: Signet-ring sinus histiocytosis is a rare and distinctive reactive disorder recently observed in the axillary lymph nodes of patients with breast carcinoma. This form of sinus histiocytosis closely resembles and can easily be confused with metastatic adenocarcinoma., Methods: To determine the incidence of this reactive process in lymph nodes from different anatomic sites, broaden its morphologic spectrum, and discuss the differential diagnosis, the authors examined lymph nodes from 316 radical prostatectomy specimens, 184 modified radical mastectomy specimens, 108 colectomy specimens, 57 gastrectomy specimens, and 27 radical hysterectomy specimens. These surgical procedures were performed to treat carcinoma of the prostate, breast, colon, stomach, and uterine cervix, respectively. A total of 9741 lymph nodes were histologically examined. The lymph nodes containing sinus signet-ring cells were stained with mucicarmine, Alcian blue, and periodic acid-Schiff stains (PAS). Immunostains for epithelial, lymphoid, and histiocytic markers were also performed. In two cases, tissue was retrieved from the paraffin block and subsequently processed for electron microscopic examination., Results: Only 4 of 316 radical prostatectomy specimens (1.2%) and 2 of 184 axillary dissections (1.08%) contained lymph nodes with signet-ring sinus histiocytosis. Of 9741 lymph nodes reviewed, 37 (24 pelvic and 13 axillary lymph nodes) had signet-ring sinus histiocytosis, for an incidence of 0.38%. Microscopically, the signet-ring histiocytes lacked nuclear atypia and were mucin negative. In two cases, clusters of histiocytes with rounded, eosinophilic, diastase resistant, PAS positive cytoplasmic globules were observed. Both types of signet-ring cells showed reactivity for histiocytic markers and were negative for cytokeratin and lymphoid markers. By electron microscopy, most histiocytes were shown to have a large empty vacuole that displaced the nucleus. Granular material was observed in some of the vacuoles. Some histiocytes exhibited a rounded cytoplasmic body composed of central electron dense, granular material and a rim of microfibrils. No lipid droplets were identified., Conclusions: Signet-ring sinus histiocytosis is a rare and distinctive reactive disorder found incidentally in the pelvic and axillary lymph nodes of patients with carcinoma of the prostate and breast, respectively. Although this histiocytic reaction mimics metastatic adenocarcinoma and signet-ring cell lymphoma, it can be identified by careful cytologic analysis together with positive reactivity for histiocytic markers, negative mucin stains, and lack of reactivity for epithelial and lymphoid markers. The etiology and pathogenesis of this unusual form of sinus histiocytosis remains unclear.

A case report is given of a very rare spontaneous mast cell tumor in the eyelid of the left eye of a female Wistar rat used in a long-term oral toxicity study. Metastasis of the tumor had occurred in the mandibular lymph nodes and in the liver. Clinically, the animal showed blepharospasm, dacryorrhoea, and exophthalmus. Hematologic findings included slight eosinophilia and a remarkable basophilia. At necropsy, a bilateral conjunctivitis was diagnosed and a tumorous mass was found in the left submandibular region. Histologically, the tumor was composed of round to polygonal cells with pale cytoplasm, containing abundant predominantly basophilic granules. The intracytoplasmatic granules stained metachromatically with Toluidine blue and immunostained positively with serotonin. Numerous eosinophils were scattered throughout the tumor and were also present in other organs. Cells with round, oval, or indented nuclei and abundant cytoplasm, containing pronounced eosinophilic granules, were found in spleen and bone marrow. They turned out to be immature stages of eosinophilic granulocytes. Characteristics of the present tumor are compared with observations on mast cell tumors in other species.

An electron microscopic (EM) study of 25 Kaposi's sarcomas (KS) (24 cutaneous lesions, 1 lymphnodal) from 23 patients, mainly sporadic in type, has enabled us to study both the spindle and endothelial cells seen by light microscopy (LM) with the conclusion that they have both a fibroblastic-like EM aspect. Both cell types manifested a spindle shape with oval and occasionally notched nuclei and a reticular pattern of nucleoli. The cytoplasm was characterized by numerous rough endoplasmic reticulum cisternae with few other organelles. The plasma membranes consistently lacked an external or basal membrane and failed to show true cell junctions. In cells delimiting erythrocytes containing spaces it was never possible to document Weibel-Palade (W.-P.) bodies or plasmalemmal vesicles. Unusual findings such as ferritin loaded phagosomes, microtubular reticular structures (MTRS), intracisternal crystalline inclusions (ICCI), multivesicular bodies (MVB), acanthosomic vesicles (AV) and test-tube inclusions or ring-shaped forms (TTI/RSF) were occasionally seen in both sporadic and epidemic KS. The authors discuss the non specific nature of these latter findings.

Background: Nuclear shape analysis of histologic sections from radical prostatectomy specimens has retrospectively predicted outcome in patients with clinically localized prostate carcinoma. If outcome could be predicted preoperatively by nuclear shape analysis, patients might be selected better for definitive surgical therapy. Morphometric analysis of preoperative biopsies, however, has not correlated positively with values obtained from analysis of prostatectomy specimens., Methods: The nuclear shapes of histologic specimens of 20 organ-confined carcinomas, 10 periprostatic fat-invasive carcinomas, 10 seminal vesicle-invasive carcinomas, and 12 lymph node-metastatic carcinomas from 52 patients who had undergone radical prostatectomy for clinically localized disease were evaluated., Results: Nuclei from areas of extraprostatic invasion or regional lymph node metastases were less round than those from the corresponding intraprostatic portion of the tumor (nuclear roundness factor (mean +/- SD) PPF, 51.2 +/- 3.1 vs. 31.2 +/- 3.2; SV, 52.4 +/- 4.1 vs. 31.6 +/- 2.5; and LN, 57.3 +/- 3.1 vs. 36.4 +/- 1.8; paired Student's t tests, P < 0.001). Cells sampled from the periphery of organ-confined tumors had a greater nuclear roundness factor (49.1 +/- 1.5) than did those sampled from the center (34.5 +/- 2.0; P < 0.001) or randomly throughout the tumor (37.8 +/- 1.6; P < 0.001). Nuclear roundness factors for all extraprostatic tumor foci and for peripheral tumor cells in organ-confined disease were similar (analysis of variance, P > 0.05). The intraprostatic portions of randomly sampled primary tumors had similar nuclear roundness factors, regardless of pathologic stage (P > 0.05). Among organ-confined carcinomas, nuclear shape was unrelated to tumor volume., Conclusions: Pathologic stage in clinically localized prostate carcinoma cannot be determined by the nuclear shape profiles of intraprostatic tumor cells. Thus, patients with a poor prognosis or high pathologic stage can be recognized only when samples for morphometric analysis include high proportions of nuclei from the extra-prostatic carcinoma and nuclei from the periphery of organ-confined carcinoma that may not be sampled routinely by prostate biopsy.

The ultrastructure and clinical significance of the basement membrane (BM) are still unclear in esophageal cancer. In this report, we examined the ultrastructure of the BM and microstructures related intercellular adhesion in squamous cell carcinoma of human esophagus using a transmission electron microscope, and investigated their clinical significance. BM was absent in 38% of the examined cases and the frequency or the presence of the microstructures of cancer cells of the infiltrating margin (CCIM) was negatively related to the presence of BM (BM-P); CCIM of BM-P tumors often had smaller number per cell of desmosomes and cytoplasmic processes. These results indicate that CCIM of BM-P tumor are in an 'inconvenient status' for tumor cells to form a firm group. In the intercellular space between CCIM and BM or surrounding stromal cells, all of the CCIM of BM-P tumors had hemidesmosomes, but not those of BM absent (BM-A) tumors. Though no statistical significant difference was found in our clinical observation between BM-P and BM-A tumors, the present study suggested that a considerable proportion of cancer cells have abnormal intercellular adhesiveness via a mechanical mechanism related to the presence or absence of BM.

Background: Nucleolar organizer regions (NORs) are loops of ribosomal DNA that occur in nucleoli and that transcribe to ribosomal RNA. NORs have been identified by means of the Ag-NOR technique in routinely processed tissues, and were found to be of discriminative value between some types of benign and malignant lesions., Methods: Follicular lesions of the thyroid (17 adenomas and 25 carcinomas) were examined. Ten normal thyroids served as the control group. All slides were stained by the Ag-NOR technique and the number of Ag-NOR dots were counted in 50 randomly selected cells. The mean number of Ag-NORs was calculated for each case. Data were statistically analyzed by the Student's unpaired t test., Results: The mean Ag-NOR counts were statistically higher in follicular carcinomas as compared to either follicular adenomas or the normal thyroid. Higher Ag-NOR counts were found in the more aggressively behaving tumors., Conclusions: It is suggested that the Ag-NOR technique could be of use as an adjunct to diagnostic histopathology and as an indicator of biologic behavior in follicular tumors of the thyroid.

The fine needle aspiration findings in a lymph node involved by signet-ring cell melanoma, a very rare variant of malignant melanoma, are reported. The patient had a history of superficial spreading melanoma of the right foot, treated 10 years earlier by below-the-knee amputation. He presented with a right groin mass. Fine needle aspiration of the mass yielded poorly cohesive, large cells with eccentric nuclei and abundant, eosinophilic cytoplasm; many of them exhibited a signet-ring appearance. Melanin pigments were identified in a small proportion of tumor cells, and a diagnosis of metastatic melanoma was made. The subsequent lymph node excision revealed a metastatic tumor composed of polygonal and signet-ring cells that were positive for S-100 protein and HMB-45 but not cytokeratin. Nearly all reported cases of signet-ring cell melanoma occurred as metastatic or recurrent disease. It is important not to mistake signet-ring cell melanoma for adenocarcinoma in aspiration cytology, and a constellation of clinical features and of histochemical and immunohistochemical findings enables a correct diagnosis to be reached.

The state of the inguinal nodes is a major prognostic factor in vulvar carcinoma. Because of new surgical trends with selective inguinal lymphadenectomy, the preoperative evaluation of inguinal lymph nodes is essential for adequate treatment of vulvar carcinoma. To evaluate the adequacy of clinical examination and high-frequency transducer sonography in detecting metastatic inguinal lymph nodes, we studied 25 patients with vulvar malignancy who underwent operation. Histopathologically proved lymph node metastases were found in 11 (22%) of 50 inguinal areas studied. All of the suspected metastases were in patients with stage III-IV disease. The inguinal lymph node metastases were found by sonography in nine (82%), by preoperative palpation in one (9%), and by operative palpation in six (55%) of 11 areas. The difference between sonography and palpation was statistically significant (P < 0.01). The sensitivity and specificity were 82% and 87% for sonography, 9% and 100% for preoperative palpation, and 55% and 90% for operative palpation.

The aim of the present study was to evaluate the diagnostic value of electron microscopy (EM) performed on Surecut biopsies from patients without known primary tumour. The material consisted of 108 consecutive biopsies, obtained over a period of two years, from patients with tumour(s) in the liver or lymph nodes (on the neck, in the axilla or retroperitoneum). From each patient fine needle aspirations and Surecut biopsies for light microscopy and electron microscopy were taken. Only biopsies in which material for both electron microscopy and light microscopy was sufficient were included (60%). Immunohistochemical reactions were performed on paraffin sections when indicated. Final diagnoses were confirmed on surgically removed specimens and/or autopsies. Electron microscopy was necessary for obtaining the final histological diagnosis in 15% of the cases. It is therefore recommended to obtain additional ultrasound guided biopsies for EM from cancer patients with tumours in the liver or lymph nodes in cases where the primary origin of the tumour is unknown.

The intra-patient variations of some clinically relevant quantifiable features, between axillary lymph node metastases were evaluated in 44 breast cancer patients. In all lymph node metastases detected (range 2-33 per patient), the mitotic figures were counted, the volume percentage epithelium was assessed and the mean nuclear area was measured. The intra-patient variation for each quantifiable feature was expressed by the coefficient of variation (CV). Since the measurement techniques used introduce a certain, well known variation themselves because of sampling and measurement errors, the CVs found had to be greater than methodological tolerance limits (established in previous studies) to be interpreted as indicating biological variation. The CVs exceeded the methodological tolerance limits in 86% of the cases for the mitotic count, in 48% of the cases for the volume percentage epithelium, and in 47% of the cases for the mean nuclear area. This indicated that in these cases, the variation found in the quantifiable features could not be explained by sampling or measurement errors and should be regarded as real biological variation. Furthermore, the variation in the quantifiable features studied showed a significant positive correlation with the number of lymph node metastases. Thus, there may be considerable intra-patient variation in quantifiable features between axillary lymph node metastases in breast cancer. This may indicate that these lymph node metastases originate independently from different clones within the primary tumour, that they are independently formed in different stages of tumour development, or that they, as an expression of intrinsic tumour heterogeneity, may develop in different directions from the start.

We investigated for the first time the relationships among all the different steroid receptor classes and between steroid receptor status and lymph node involvement in laryngeal carcinoma. Androgen (AR), oestrogen (ER), progesterone (PR) and glucocorticoid (GR) receptors were assayed in the high-speed soluble fraction and in the nuclear extract from 73 carcinomas of the larynx. Forty-one, 26, 15, and 13 tumours expressed cytosolic GR, ER, AR, and PR, respectively, while 33, 26, 13 and 13 biopsies were nuclear-positive for GR, ER, AR, and PR, respectively. Data obtained in histologically-proven non-cancerous larynx (N = 20) compared to those obtained in the malignant specimens showed a significant loss of ER and PR in cancerous larynx over that in the non-cancerous tissue. Lymph node metastases were evaluated in only 53 of the 73 patients and they were noted in 22 cases (41.5%). No significant relationships were found either among the different classes of steroid receptors or between steroid receptors and lymph node involvement. Despite the apparent absence of any interrelationships among the different receptors or tendency towards metastasis, the presence of steroid receptors would justify the use of hormonal manipulations which could be effective in the management of this disease.

In an attempt to better understand the biologic behavior of neoplastic cell metastasis, a histochemical study with the use of six different lectins and a monoclonal antibody against human pulmonary surfactant apoprotein (PE-10) was carried out on primary adenocarcinomas of the lungs and their regional (usually lymphatic to lymph nodes or contralateral lung) and distant (usually hematogenous to extrathoracic organs) metastatic lesions of 54 postmortem cases. Primary pulmonary adenocarcinomas were classified further into acinar, papillary, and solid types according to WHO histological typing. Acinar type primary adenocarcinoma of the lungs showed significantly higher (p less than 0.05) binding reactions to Ricinus communis-I (RCA-I) and Ulex europaeus-I (UEA-I) lectins than solid type adenocarcinoma. With six different lectins, concordantly positive reactions between primary pulmonary adenocarcinomas and their lymphatic and hematogenous metastases were seen in 67% or more cases, and with soybean agglutinin (SBA) and UEA-I the concordance rates between primary and lymphatic metastases (lymph nodes and contralateral lungs, respectively) were significantly higher (p less than 0.05) than those between primary and hematogenous metastases. With PE-10 immunohistochemistry, concordantly positive reactions between primary and metastases were low, especially in cases of distant hematogenous metastases (25%), but the statistical significance of differences was missed by narrow margins. With alcian blue PAS-stain, concordantly positive reactions of mucin production between primary adenocarcinomas and both lymphatic and hematogenous metastases were high (92%), but there was no evidence of correlation between lectin bindings and alcian blue-PAS reactions to either primary or metastatic lesions of pulmonary adenocarcinomas.

The prognostic value of nuclear morphometry in nasopharyngeal carcinoma (NPC) was investigated in 28 patients. Seven morphometric nuclear variables were measured on 100 randomly selected tumor cells in nasopharyngeal biopsies from 18 patients with NPC confined to the nasopharynx. The same variables were measured in 6 patients with metastatic NPC, as well as in lymph node biopsies from 4 patients with metastatic NPC. Nuclear area, nuclear perimeter, long and short nuclear axes, nuclear form factor, nucleolar area, and the ratio of nucleolar area to nuclear area were all measured. Volume-weighted mean nuclear volume was also obtained. Tumor cells from patients with NPC confined to the nasopharynx had significantly larger mean nuclear areas, perimeters, and volume-weighted mean nuclear volumes but significantly smaller nucleolar to nuclear area ratios than tumor cells from patients with nodal metastases. Assessment of nuclear form factor and diameters did not differentiate the two groups.

Extracranial metastases of a poorly differentiated medulloblastoma in a 12-year-old girl were studied by thin section transmission electron microscopy and immunohistochemistry. The primary tumor did not show any differentiation as revealed by immunohistochemistry. On the contrary, the metastatic tumor cells and their processes disclosed features of neuroblastic differentiation when examined ultrastructurally: microtubules, dense core vesicles, and abortive synaptic ribbons. Several dystrophic neurites containing altered subcellular organelles were also found. Furthermore, few processes contained concentric arrays of paired membranes. This report is the first to clearly show the neuronal differentiation of extracranial metastases of poorly differentiated medulloblastoma. We speculate that metastases of medulloblastomas outside the neuraxis behave analogously to medulloblastoma explants cultured in vivo.

A morphometric study of subcellular structures in human primary breast tumors (of the ductal infiltrating type) and their synchronous lymph node metastases was carried out using planimetry and stereology. Each primary neoplasm was compared separately with its axillary metastatic growth in order to detect differences in the quantitative estimates of their subcellular components. A set of 24 morphometric parameters was used to quantitatively describe each neoplastic cell profile. Although some subcellular parameters showed significant differences between the cells of a primary tumor and its metastases, no parameter was found to be consistently altered in all cases. No consistent increase or decrease in the values of the affected parameters was observed in the metastases. More than being due to the expression of a biologically variant (more-or-less differentiated) metastatic phenotype, the differences in stereologic parameters detected in metastatic cells appear to reflect the existence of different functional states of the same cell type.

We present six cases in which lymphadenopathy was the initial manifestation of malignant mesothelioma. In five cases, the primary tumor was located in the peritoneum; it was located in the pleura in the sixth. The involved lymph nodes were cervical in four cases, mediastinal in one, and inguinal in one. The morphologic, immunohistochemical, and ultrastructural features were typical of malignant epithelial mesothelioma. A review of the literature disclosed only one previously documented example of this phenomenon. When confronted with a lymph node involved by metastatic tumor, pathologists should be aware that malignant mesothelioma can present initially in the form of lymphadenopathy and include this possibility in the differential diagnosis.

We report on the clinical and pathologic features of 32 lesions diagnosed as malignant spindle cell and epithelioid cell nevus (S&E nevus). Because of the clinical or initial histopathologic diagnosis of malignant melanoma, six patients had lymph node dissection. Three of these patients also had an enlarged lymph node. In all six cases, metastatic spindle or epithelioid cells were found in at least one of the resected lymph nodes. Of the 30 patients with follow-up information, including all six patients with lymph node metastases, all are alive and well. No recurrences or further metastases have been found. On histopathologic reevaluation, all the lesions had features of S&E nevi. Study of these cases suggests that although some lesions with features of S&E nevi may involve local lymph nodes, widespread metastases do not result.

DNA-estimations, done by flow-through-cytophotometry, were performed in 18 malignant tumors of testis. Aneuploid stemlines which are specific for cancers were found in 17 cases. The only exception was a so called "occult seminoma". It showed only a small difference between the stem-line of tumor and normal cells of testis. So, by using DNA-estimation, it was possible to make a correct diagnosis all 18 patients, suffering from tumor of the testis. The aneuploid stem-lines of seminomas did not differ from those of other cancers. The type of proliferative behavior seems to be a criterion for prognosis. Lymphatic nodes with and without formation of metastases very clearly showed differences in the DNA-content of their nuclei.

A case of metastatic balloon cell melanoma is presented. The balloon cells are ultrastructurally characterized by the presence of numerous cytoplasmic vacuoles and abnormal melanosomes, which confirm their melanocytic origin. The study supports the concept that the cytoplasmic vacuoles represent grossly dilated melanosomes. The value of electron microscopic examination is emphasized in order to distinguish these lesions from other malignant clear cell tumors.

Sixty-three breast carcinomas were examined by electron microscopy to determine the frequency of calcium hydroxyapatite (apatite) within tumor lumina. Twenty-one adenocarcinomas contained apatite in intracytoplasmic and/or intercellular lumina. Well-differentiated tumors exhibited a higher incidence of apatite (44%), while only 20% of the poorly differentiated tumors contained apatite (gamma = +.22). There was no apparent correlation between the presence of apatite and a positive estrogen receptor assay. Ninety-eight adenocarcinomas of other than breast origin (previously processed for electron microscopy) were examined, revealing 2 cases containing apatite in the appropriate locations. The tissue of origin in one case was determined to be ovarian, while the origin of the second case remains undetermined. The ultrastructural finding of apatite in lumina of adenocarcinoma appears to be unusual in that it has only been observed in breast carcinomas and certain ovarian tumors. The presence of apatite within the lumen in addition to other characteristics of an adenocarcinoma may suggest the breast as the primary site.

In a series of 112 cases of breast carcinoma with metastases to the axillary nodes, the mean nuclear area (MNA) in the nodal tumour showed a relationship to survival time that was similar to that given by histological grading. Combination of the 2 measurements increases the possible use of the heterogeneity of the material, leading to a more individualized prognosis.

A lymph node containing metastatic medullary carcinoma of the thyroid gland was examined immunohistochemically for the presence of calcitonin by light and electron microscopy. Electron microscopy showed dense, selective labeling of the tumor-associated amyloid fibrils and labeling of the scanty intracytoplasmic neurosecretory granules. By light microscopy, a few tumor cells showed strong staining, whereas the amyloid fibrils showed equivocal staining.