Major Growth Patterns Research Articles

Lymphocyte-Rich Spindle Cell Thymoma: Clinicopathologic, Immunohistochemical, Ultrastructural and Molecular Genetic Study of 80 Cases.

A study of 80 cases of spindle cell thymoma in which the spindle cell component was overshadowed by massive numbers of stromal lymphocytes is presented. The patients were 38 women and 42 men, aged 8 to 81 years (mean=54 y). All tumors presented as an anterior mediastinal mass; 5 patients had myasthenia gravis and one had Good syndrome. The tumors were well-circumscribed, encapsulated, and measured 2.9 to 26.0 cm in greatest diameter (mean=7.3 cm). Using modified Masaoka staging, 66 tumors were stage I, 10 were stage IIa, 2 were stage III and 1 was stage IV. Histologically the tumors were characterized by a predominant lymphocytic population admixed with scattered small spindle epithelial cells. The neoplastic spindle cells in these tumors demonstrated 2 major growth patterns: in 33 cases, the tumors were exclusively composed of dense sheets of lymphocytes containing scattered spindle cells resembling a lymphocyte-rich thymoma (WHO type B1); in the remaining cases the tumors showed admixtures of a predominantly lymphocytic component with areas that were lymphocyte-poor and contained a pure spindle cell population similar to WHO type A. Immunohistochemical stains and electron microscopy corroborated the spindle cell morphology in both types. The GTF2I p.L424H variant was identified in 53 of 63 (84%) cases analyzed. Clinical follow-up in 27 cases showed that most of the tumors behaved in an indolent manner. Our study expands the spectrum of spindle cell thymoma by demonstrating the existence of cases that are predominantly composed of lymphocyte-rich elements and lack areas with a pure (lymphocyte poor) spindle cell morphology.

Mathematical modeling of tumor surface growth with necrotic kernels

A two‐dimensional tumor‐immune model with the time delay of the adaptive immune response is considered in this paper. The model is designed to account for the interaction between cytotoxic T lymphocytes (CTLs) and cancer cells on the surface of a solid tumor. The model considers the surface growth as a major growth pattern of solid tumors in order to describe the existence of necrotic kernels. The qualitative analysis shows that the immune‐free equilibrium is unstable, and the behavior of positive equilibrium is closely related to the ratio of the immune killing rate to tumor volume growth rate. The positive equilibrium is locally asymptotically stable when the ratio is smaller than a critical value. Otherwise, the occurrence of the delay‐driven Hopf bifurcation at the positive equilibrium is proved. Applying the center manifold reduction and normal form method, we obtain explicit formulas to determine the properties of the Hopf bifurcation. The global continuation of a local Hopf bifurcation is investigated based on the coincidence degree theory. The results reveal that the time of the adaptive immune system taken to response to tumors can lead to oscillation dynamics. We also carry out detailed numerical analysis for parameters and numerical simulations to illustrate our qualitative analysis. Numerically, we find that shorter immune response time can lead to longer patient survival time, and the period and amplitude of a stable periodic solution increase with the increasing immune response time. When CTLs recruitment rate and death rate vary, we show how the ratio of the immune killing rate to tumor volume growth rate and the first bifurcation value change numerically, which yields further insights to the tumor‐immune dynamics.

A Study on the Somatotype Characteristics of Adolescent Girls between the Ages of 13 and 18

This study analyzes the characteristics of somatotype changes of girls from the ages of 13 to 18 that provide basic data on clothing construction for middle and high school girls. We use data obtained from body measurements of 1,590 adolescent girls 13 to 18 years of age provided in the 6th national anthropometric survey report. The differences among the age groups for 56 direct measurements were analyzed by ANOVA, and the structures of the differences by SNK (Students-Newman-Keuls test) were analyzed. The two major growth ages were ‘ages 13-14’ and ‘ages 15-16’. The first major growth ages focused on all measurement items of height, length, circumference, breadth, depth and other items. The second one focused on measurement items of height and length of torso, circumference, and breadth of lower body. The major growth pattern of the age groups was ‘ages 13<14&15<16&17&18’ which appeared focused on the height and length items of upper body and torso, the width items of lower body and the circumference items of upper body and lower body. The measurement items of front length like waist front length, N.P. to B.P to waistline, N.P. to B.P., and B.P. to B.P. showed the growth pattern for ‘ages 13<14<15<16<17&18’.

Angiosarcoma of the Liver: Clinicopathologic Features and Morphologic Patterns.

Angiosarcoma is a rare malignant neoplasm of the liver. The various morphologic patterns seen with angiosarcomas of the liver have not been systematically studied and their recognition remains a major diagnostic challenge. In order to provide more comprehensive data on the morphologic patterns, angiosarcomas that had been diagnosed between 1996 and 2016 at a large medical referral center were reviewed. The major growth patterns were classified as sinusoidal (non-mass forming) versus mass forming. The mass-forming cases were further subdivided into epithelioid, spindled, or vasoformative. The study identified 21 patients with primary hepatic angiosarcoma: 13 men and 8 women. The ages ranged from 26 to 89 years. Seventeen angiosarcomas were mass-forming tumors, of which 9 showed predominantly vasoformative growth. Most of these vasoformative cases (6/9) were composed of small vessels, 2 cases had slit-like vascular spaces, and one case showed a mixture of small and large vessels. There were 7 mass-forming angiosarcomas without vasoformation: 3 had an epithelioid morphology and 4 were composed primarily of spindled cells. The final mass-forming tumor showed a mixture of vasoformative and nonvasoformative areas. Four of 21 cases were non-mass forming and showed either diffuse sinusoidal infiltration (N=2) or prominent peliotic changes (N=2). Finally, 3 uncommon patterns were identified. One case showed nodules of spindle cells arranged in prominent whorls in a background of loose connective tissue with abundant inflammation. A second case arose in the setting of the Blue Rubber Bleb Nevus Syndrome and showed numerous tumor nodules with an architectural pattern that resembled infantile hemangioma, some with areas of atypia consistent with malignant transformation to angiosarcoma. The third unusual pattern showed multiple nodules of thin walled large caliber vascular proliferations, some of which showed atypia that reached the level of angiosarcoma. The results from this study indicate that the majority of hepatic angiosarcomas are mass forming (two third of cases), a pattern that is recognizable on H&E when vasoformative, but can mimic carcinoma or undifferentatied sarcomas when nonvasoformative (one third of cases). The sinusoidal patterns are particularly challenging and are frequently missed on initial review. Finally, we describe several unsual patterns of angiosarcoma. Awareness of these classic and rare morphologic patterns can help make the diagnosis of angiosarcoma.

Comparing interactions in three-fold symmetric molecules at solid–air interface

Drop-casted ultra-thin films of Benzene-1,3,5 -tricarboxaldehyde (TCA) and Trimesic acid (TMA) are studied using scanning tunneling microscopy (STM) and atomic force microscopy (AFM) to understand the molecular as well as the global nature of molecular assembly on highly oriented pyrolytic graphite (HOPG). We compare the self-assembly of TMA with that of TCA, which offers relatively weak inter-molecular interaction while keeping the same symmetry. While TMA molecules assemble into a porous chicken-wire pattern through strong hydrogen bonding, TCA forms compact assembly driven by a balance of weak hydrogen bonding interactions and high packing density. Major growth patterns in TMA and TCA are isotropic in nature due to same inter-molecular interaction along all molecular compact directions of their adlayer. In addition to the isotropic growth, we also observe anisotropic growth patterns, where the inter-molecular interactions have different magnitude along different molecular compact directions. A substantial amount of amorphous growth is also observed for both molecules. The diversity in the growth behavior for both molecules is understood using inter-molecular interactions for TMA/TCA.

Basal Cell Carcinoma Progression Correlates With Host Immune Response and Stromal Alterations: A Histologic Analysis

Neoplastic progression is characterized in part by escape from immune surveillance and formation of growth-permissive stroma. Basal cell carcinoma (BCC) can be subclassified into low- and high-risk types for local recurrence. To determine whether these types of BCC correlate with alterations in local host immune response and stroma and whether these changes follow stepwise histologic progression from low- to high-risk subtypes, we assessed the clinicopathologic features in 175 consecutive primary (nonrecurrent) BCC excision specimens. BCCs exhibited a significantly higher frequency of mixed rather than homogeneous growth patterns (76% vs. 24%, P=0.0001). Nodular (84%) was the most common pattern identified followed by superficial (77%), infiltrative (27%), morpheic (5%) and micronodular patterns (4%). Only superficial (12% of all BCC) and nodular (12%) patterns were identified in BCC with a homogeneous histologic phenotype. Micronodular and infiltrative-morpheic patterns were not identified together in mixed patterned BCCs, and these high-risk types were contiguous with nodular BCC. Superficial predominant BCC (major growth pattern) was significantly associated with trunk and extremity location (76%) and skin without solar elastosis (82%), whereas BCC harboring a nodular growth pattern component was significantly associated with a head and neck location (63%) and the presence of adjacent solar elastosis (all P< or =0.03). Significant correlations were identified for BCC subtypes with inflammatory and stromal alterations: superficial BCC with old regression and moderate to dense peritumoral lymphocytic infiltrates; high-risk types correlated with active regression; infiltrative and morpheic BCC with fibrosing tumor stroma; and micronodular BCC with loss of both host inflammatory and stromal tumor responses. Evaluating the theoretical histologic stepwise model of BCC progression (superficial-to-nodular-to-micronodular, or superficial-to-nodular-to-infiltrative-to-morpheic BCC types) revealed significant linear correlations with host response and alterations of tumor stroma (r=0.54, P=0.0001). BCC exhibit distinct epithelial-stromal-inflammatory patterns that correlate with BCC subtype and tumor progression. This ostensible pathway of diminishing host response and gain of permissive tissue environment highlights neoplastic evolution from low to high risk for local recurrence of BCC and implicates a histologic continuum reflecting dynamic host-BCC interactions.

Benign mimickers of prostatic adenocarcinoma

The diagnosis of prostatic adenocarcinoma, especially when present in small amounts, is often challenging. Before making a diagnosis of carcinoma, it is prudent for the pathologist to consider the various benign patterns and processes that can simulate prostatic adenocarcinoma. A useful method of classifying benign mimickers is in relationship to the major growth patterns depicted in the classical Gleason diagram. The four major patterns are small gland, large gland, fused gland and solid. Most mimickers fit within the small gland category and the most common ones giving rise to false-positive cancer diagnosis are atrophy, post-atrophic hyperplasia, atypical adenomatous hyperplasia and seminal vesicle-type tissue. A number of other histoanatomic structures such as Cowper's gland, verumontanum mucosal glands, mesonephric glands and paraganglionic tissue may be confused with adenocarcinoma. Additionally, metaplastic and hyperplastic processes within the prostate may be confused with adenocarcinoma. Furthermore, inflammatory processes including granulomatous prostatitis, xanthogranulomatous prostatitis and malakoplakia may simulate high-grade adenocarcinoma. Atypical adenomatous hyperplasia (adenosis), a putative precursor of transition zone adenocarcinoma, has overlapping features with low-grade adenocarcinoma and may cause problems in differential diagnosis, especially in the needle biopsy setting. The pathologist's awareness of the vast array of benign mimickers is important in the systematic approach to the diagnosis of prostatic adenocarcinoma. Knowledge of these patterns on routine microscopy coupled with the prudent use of immunohistochemistry will lead to a correct diagnosis and avert a false-positive cancer interpretation.

A Spontaneous Rat Ovarian Cystoadenocarcinoma with Papillary Growth to the Serosa.

A spontaneous ovarian cystadenocarcinoma with papillary growth to the serosa in a 66-week-old F344 rat was investigated morphologically and compared with a rat abdominal mesothelioma. Macroscopically, a large white soft mass was found in the right ovarian area with disseminated small nodules to the serosa and cloudy bloody-ascites in the abdominal cavity. Metastases to the lungs and lymph nodes were noted. Histologically, major growth patterns of the ovarian mass were tubular, cystic and/or papillary. The tubular areas were characterized by atypical cuboidal and/or columnar epithelial cells, with various amounts of stroma dividing glands. Cystic areas consisted of single or multiple cysts lined by uniform epithelial cells with intra-cystic papillary growth, supported by abundant hyaline-like stroma. Continuing from the ovarian mass, tumor cells were spread on the mesentery and omentum. Superficially, papillary projections resembling those of a mesothelioma were apparent. In deep areas, tubular structures consisting of epithelial cells were surrounded by various amounts of connective tissues. In the mesothelioma, collagen fibers were diffusely distributed around clustered or individual tumor cells. Since the histologic features strongly suggested a derivation from ovarian surface epithelium, we diagnosed this case as an ovarian cystadenocarcinoma with papillary growth to the serosa. Immunohistochemical results did not provide any clear specific reactions to distinguish ovarian cystadenocarcinomas from mesotheliomas.

From the archives of the AFIP. Leiomyosarcoma of the retroperitoneum and inferior vena cava: radiologic-pathologic correlation.

Leiomyosarcoma is the second most common primary retroperitoneal tumor in adults. Retroperitoneal leiomyosarcoma exhibits three major growth patterns: (a) completely extravascular (extraluminal) (62% of cases), (b) completely intravascular (intraluminal) (5% of cases), and (c) extra- and intraluminal (33% of cases). The usual clinical manifestation is a large abdominal mass. Intraluminal leiomyosarcoma may be accompanied by symptoms referable to venous thrombosis. The variable gross features and potential for intravascular extension result in various radiologic appearances, the most common being a large, partially necrotic soft-tissue mass in the retroperitoneum with or without extension into the inferior vena cava. Computed tomography and magnetic resonance imaging typically show a nonfatty, necrotic retroperitoneal mass and a vascular component when it is present. Ultrasound and angiography may also be useful, especially if vascular involvement is suspected from other imaging studies. Treatment of choice is surgical excision, which is frequently impossible due to the invasiveness of the tumor. Prognosis is related to extent of invasion and the adequacy of resection. Long-term prognosis is poor, and most patients die of local recurrence or distant metastasis.

Effects of early environments on monkey cortex neuroanatomical changes following somatomotor experience: effects on layer III pyramidal cells in monkey cortex.

Sixteen infant stumptail monkeys were reared to 6 months under four conditions. Behaviors and cortical neuroanatomy were compared. Earlier studies showed effects on stellate cell dendrites. Here are reported the results in six cortical areas on basilar dendrites of layer III pyramidal cells. Basilar dendrites show significantly larger numbers (p less than .05) of branching for motor I cortex under condition 3 associated with the greatest skills and amount of activity in climbing, swinging, and grasping of objects. Visual cortex was not significantly altered by the rearing conditions, but the basilar dendrites showed less branching than in the five other areas of cortex sampled. It is concluded that genetic factors are responsible for the major growth patterns and that environmental factors contribute to quantitative increases or decreases in the branching of dendrites and therefore the finer tuning of neural interconnections.

Carcinoids: the association of histologic growth pattern and survival.

There are five generally accepted carcinoid histologic growth patterns, i.e., insular, trabecular, glandular, undifferentiated, and mixed. To determine their possible prognostic significance, a panel of pathologists studied the growth patterns of 138 carcinoids collected from an Eastern Cooperative Oncology Group carcinoid advanced stage disease chemotherapy investigation. Survival times were measured from date of initial pathologic diagnosis of carcinoid disease to date of either death or last follow-up. Significant differences were observed in survival times between the five major growth patterns (P less than 0.001). Within the mixed growth pattern group, significant differences in survival time were also observed (P approximately 0.05). In decreasing order of median survival time in years, the growth patterns ranked as follows: mixed insular plus glandular, 4.4; insular, 2.9; trabecular, 2.5; mixed insular plus trabecular, 2.3; three pooled low incidence rate mixed growth patterns, 1.4; glandular, 0.9; and undifferentiated, 0.5. Histologic growth patterns are recommended as a stratification factor in future studies of this disease.

Longitudinal somatometrical study on the growth patterns of newborn Japanese monkeys

Growth of Japanese macaques during their first year was analyzed longitudinally, using body measurements. Measurements of 44 somatometrical characters were taken on seven animals. Work with the newborn data produced a formula which fits well. The formula is: y=a (x+b)n (y=size, x=age). At first, growth was analyzed, character by character, using birth sizes and incremental increases. The results show a major growth pattern for many characters: increments vary inversely with birth size. Application of the growth formula produced two further insights: (1) growth pattern is not so simple as imagined from the birth size-increment pattern; and (2) the characters which deviate from the birth size-increment pattern have large growth only at the earliest period (in few months), in spite of their small size. Sex differences were clear within the first year, especially for characters which differ greatly between adults.