TGF-β1 is a multi-functional cytokine that plays an important role in breast carcinogenesis. Critical role of TGF-β1 signaling in breast cancer progression is well documented. Some TGF-β1 polymorphisms influence its expression; however, their impact on breast cancer risk is not clear.
We analyzed 1222 samples in a candidate gene-based genetic association study on two distantly located and ethnically divergent case-control groups of Indian women, followed by a population-based genetic epidemiology study analyzing these polymorphisms in other Indian populations. The c.29C>T (Pro10Leu, rs1982073 or rs1800470) and c.74G>C (Arg25Pro, rs1800471) polymorphisms in the TGF-β1 gene were analyzed using direct DNA sequencing, and peripheral level of TGF-β1 were measured by ELISA.
c.29C>T substitution increased breast cancer risk, irrespective of ethnicity and menopausal status. On the other hand, c.74G>C substitution reduced breast cancer risk significantly in the north Indian group (p = 0.0005) and only in the pre-menopausal women. The protective effect of c.74G>C polymorphism may be ethnicity-specific, as no association was seen in south Indian group. The polymorphic status of c.29C>T was comparable among Indo-Europeans, Dravidians, and Tibeto-Burmans. Interestingly, we found that Tibeto-Burmans lack polymorphism at c.74G>C locus as true for the Chinese populations. However, the Brahmins of Nepal (Indo-Europeans) showed polymorphism in 2.08% of alleles. Mean TGF-β1 was significantly elevated in patients in comparison to controls (p<0.001).
c.29C>T and c.74G>C polymorphisms in the TGF-β1 gene significantly affect breast cancer risk, which correlates with elevated TGF-β1 level in the patients. The c.29C>T locus is polymorphic across ethnically different populations, but c.74G>C locus is monomorphic in Tibeto-Burmans and polymorphic in other Indian populations.
Benign epithelioid peripheral nerve sheath tumor, a rare entity is an umbrella term describing benign, neural origin tumors with epithelioid morphology. Clinically indistinguishable from other benign cutaneous lesions, histopathology offers the only source of accurate diagnosis. Morphologic mimics include many benign and malignant soft tissue lesions. Besides a predominant epithelioid component, the lesion can also show a fair share of spindle cells. A circumscribed nodular tumour of low mitotic activity, it often exhibits areas resembling schwannoma or neurofibroma. An awareness of this entity and its varied morphological aspects helps to arrive at the correct diagnosis and hence avoid unnecessary extensive surgical procedures. This case presents features of this benign tumor which occurred in a 47 years old man.
Benign; epithelioid; nerve sheath; peripheral
Aggressive angiomyxomas are uncommon mesenchymal tumours which most often arise in the perineal and the pelvic regions in women. Extragenital aggressive angiomyxonas are extremely rare. We are reporting a young male with an aggressive angiomyxoma which involved the axillary region and extended into the anterior chest wall, which demonstrated its characteristic histomorphological features. The diagnosis was confirmed by immunohistochemistry. A careful histological examination, along with immunohistochemistry, aids in diagnosing this lesion and differentiating it from tumours which have similar histologies.
Aggressive angiomyxoma; Extragenital; Chest wall; Axilla
Non-Hodgkin’s Lymphomas (NHLs) which are associated with the Acquired Immunodeficiency Syndrome (AIDS) are heterogeneous. Plasmablastic Lymphoma (PBL) was first recognized as an aggressive, invariably fatal subtype of Non-Hodgkin’s Lymphoma which occurred mostly in patients with AIDS, with distinct histomorphologic and immunophenotypic findings, which affected the jaw and the oral mucosa exclusively. Subsequently, there have been case reports which have described extra-oral plasmablastic lymphomas in the lung, jejunum, caecum, nasal mucosa, etc. We are reporting a case of this rare subtype of diffuse large B-cell lymphoma which presented as a soft tissue mass, which we believe is the first case to be diagnosed by FNAC.
Extra-oral; Plasmablastic lymphoma
The epithelioid variant of malignant peripheral nerve sheath tumours is a rare histological entity, and the occurrence of a malignant peripheral nerve sheath tumour in the skull base is even more unusual. We report a case of a 52-year-old man who presented with reduced hearing in the left ear, giddiness and left-sided facial weakness of short duration. He was a known hypertensive. On examination, left-sided 7th to 12th cranial nerve palsies were noted. Computed tomography (CT) and brain magnetic resonance imaging (MRI) were reported as an ill-defined heterogeneously enhancing mass left skull base suggestive of chondrosarcoma. Left tympanotomy and biopsy of the lesion were carried out. On light microscopy and immunohistochemical examination of the biopsy, a diagnosis of epithelioid malignant peripheral nerve sheath tumour was established. The patient underwent left extended modified radical mastoidectomy and selective neck dissection. Histopathological study of the resected surgical specimen confirmed left-sided extensive tumour involvement of skull base structures, as well as neck nodal metastases.
Nerve sheath neoplasm; malignant schwannoma; skull base
Urethral mucosa with intestinal metaplasia and dysplasia is a rare occurrence. To date only a single case has been reported in a male with long-standing urethral stricture. We present a 33-year-old female with polypoid intestinal metaplasia and dysplasia of the external urethral meatus in the absence of an inciting factor. Intestinal metaplasia of the urethral mucosa may undergo dysplasia, emphasizing the necessity of a high degree of clinical suspicion and vigilant pathological examination of these lesions.
Infantile myofibroma is a rare and benign tumour of children presenting in the head and neck region. Rendering a final diagnosis of infantile myofibroma can be challenging in the light of nonspecific clinical, radiological findings and its histopathological similarities with a number of neoplasms especially spindle cell tumours. In this paper we discuss a case of infantile myofibroma in a 2-month-old infant, enumerating the various differential entities that have to be eliminated in reaching its specific diagnosis and highlighting the importance of immunopositivity to vimentin and smooth muscle actin (SMA) in establishing its myofibroblastic differentiation.
Chorioangioma is a benign angioma of placenta arising from chorionic tissue. Large chorioangioma has unfavourable effects on both mother and fetus. We describe a case with large chorioangioma that had a poor outcome on the fetus. We also reviewed the literature on prognostic factors affecting fetal outcome.
Extraosseous Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) is an uncommon, aggressive, and malignant tumor with a poor patient outcome. Its occurrence in the lesser sac is a rare event and to the best of our knowledge, has not been previously described. The present case was clinically and radiologically misdiagnosed as a pancreatic tumor/gastrointestinal stromal tumor. Histopathology revealed a tumor with "small round cells" that were positive for CD99, confirming the diagnosis of ES/PNET. This report highlights the importance of considering Ewing's sarcoma in the differential diagnosis of intraabdominal, extraintestinal masses.
CD99 protein; Sarcoma, Ewing; Extraosseous; Neuroectodermal tumors, primitive
Aims of the study were to evaluate the expression Cytokeratin 5/6(CK5/6) and Epidermal Growth Factor Receptor (EGFR) among triple negative breast cancers and high grade infiltrating duct carcinomas. Further to probe if triple negative phenotype can be a surrogate marker for basal phenotype and to correlate the expression of basal markers with disease free survivals among triple negative phenotype and high grade infiltrating duct carcinomas.
Expression of CK5/6 and EGFR were studied by Immunohistochemistry (IHC) in 31 triple negative and 19 non-triple negative high grade breast carcinomas.
21 of the 31 triple negative phenotype (67.7%) breast carcinomas and 7 out of 19 non-triple negative (36.8%) breast carcinomas showed expression of basal markers (CK5/6 and/or over-expression of EGFR). There were statistically significant associations of all the basal-like tumors with negative hormonal status. The basal markers positive phenotype subjects had a shorter disease free interval as compared to basal markers negative phenotype subjects.
Basal-like breast carcinomas constitute a unique clinical and pathological entity, characterized by high tumor grade and a propensity for lack of ER, PR and HER2 expression. Basal phenotypes have a more aggressive course than non-basal phenotype. “Triple negative” status cannot be used as a surrogate for “basal marker expression”.
breast cancer; tumor grade; basal-like; triple-negative; CK5/6; EGFR
Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts is a low grade, rare, soft tissue tumor which commonly occurs on the lower extremities of adults of either sex, though lesions in other anatomic locations have been described. We present a case of a 65-year-old female patient who presented with a left forearm swelling and underwent a wide local excision. Histopathology revealed it to be a PHAT.
Pleomorphic hyalinizing angiectatic tumor; Soft tissue neoplasms; Extremities; Excision
Carney complex is a very rare multiple neoplasia syndrome with cardiac, cutaneous, and neural tumours with a variety of pigmented lesion of skin. We are reporting a rare case of carney complex in which left atrial myxoma with superficial angiomyxoma, giant cell tumour of bone and lentigines showed a unique association. This patient underwent successful surgical excision of left atrial myxoma under cardiopulmonary bypass.
Anchorage independent growth is an important hallmark of oncogenic transformation. Previous studies have shown that when adhesion dependent fibroblasts were prevented from adhering to a substrate they underwent anoikis. In the present study we have demonstrated how anoikis resistant cells gain the transformation related properties with sequential selection of genes. We have proposed this process as a model system for selection of transformed cells from normal cells.
This report demonstrates that some fibroblasts can survive during late stages of anoikis, at which time they exhibit transformation-associated properties such as in vitro colony formation in soft agar and in vivo subcutaneous tumour formation in nude mice. Cytogenetic characterisation of these cells revealed that they contained a t (2; 2) derivative chromosome and they have a selective survival advantage in non adherent conditions. Gene expression profile indicated that these cells over expressed genes related to hypoxia, glycolysis and tumor suppression/metastasis which could be helpful in their retaining a transformed phenotype.
Our results reveal some new links between anoikis and cell transformation and they provide a reproducible model system which can potentially be useful to study multistage cancer and to identify new targets for drug development.
The common cause of mental impairment and the wide range of physical abnormalities is balanced chromosome rearrangement. As such, it is difficult to interpret, posing as a diagnostic challenge in human development. We present a unique familial case report with the paternally inherited autosomal-balanced reciprocal translocation involving chromosomal regions 8q and 18q. The etiology of the translocation, i.e. 46,XX,t(8;18)(q22.1;q22) was detected by conventional high-resolution Giemsa–Trypsin–Giemsa-banding and fluorescence in situ hybridization techniques. The father was found to be the carrier of the chromosome defect and also the same was observed in the first female child referred with a history of delayed milestone development. However, the second female child showed normal 46, XX karyotype. This is the first report of reciprocal translocation involving 8q and 18q associated with the delayed milestone development. The reason likely may be due to the rearrangement of genetic material at these breakpoints having a crucial relationship and thus manifesting developmental delay in the progeny. Accordingly, this paper also shows genetic counseling discussion for the cause.
Balanced reciprocal translocation; chromosomes 8 and 18; delayed milestones; Giemsa–Trypsin–Giemsa banding and FISH; translocation carrier