Invasive ductal carcinoma not otherwise specified (NOS) is a frequently delineated subtype of infiltrating breast carcinoma preponderantly emerging from terminal duct-lobular unit. In contrast to females, possible emergence of invasive ductal carcinoma within male breast is relatively infrequent. Majority (~80%) of instances of infiltrating duct carcinoma concur with ‘not otherwise specified’ variant which appears to be devoid of pertinent microscopic features, encountered in diverse subtypes of mammary carcinomas [1,2]. Generally a disease of elderly, postmenopausal population, tumefaction commonly emerges in women > 65 years [1,2]. Neuroendocrine differentiation with occurrence of spindle-shaped cells, carcinoid cells, plasmacytoid cells or clear cells imbued with cytoplasmic neurosecretory granules immune reactive to synaptophysin or chromogranin appears to be focal [1,2]. Genetic, hormonal or environmental factors contribute to emergence of invasive ductal carcinoma [1,2]. Hormonal factors engendering ductal carcinoma are early menarche’, delayed menopause, nulliparous state, primigravida > 30 years, obesity with postmenopausal state, occurrence of oestrogen- producing ovarian neoplasms or administration of oestrogens or combined hormone- replacement therapy with progestogens [1,2]. Hormonal induction of carcinoma breast is concurrent with intense, prolonged oestrogenic stimulation which may induce secretion of growth promoters [1,2]. Genesis of invasive ductal carcinoma breast with oral contraceptives remains debatable [1,2]. Neoplastic occurrence is common in individuals with first- degree relatives of carcinoma breast, especially with bilateral disease or preliminary tumour occurrence >50 years. Proportionate tumour emergence is enhanced with incrimination of two or more first-degree relatives [1,2]. Li-Fraumeni syndrome exhibiting germline mutations of p53 gene is associated with carcinoma breast. Chromosomal mutations of BRCA1 and BRCA2 genes may appear in familial carcinoma breast exemplified in young individuals [1,2]. Cowden's disease or multiple hamartoma syndrome is an autosomal dominant disorder arising due to mutation of 10q gene and expounds possible invasive ductal carcinoma or ductal carcinoma in situ- breast in women ~ 50 years, in addition to benign cutaneous neoplasms [1,2]. Heterozygous carriers of ataxia-telangiectasia may depict carcinoma breast by 50 years [1,2]. In contrast to Caucasians, black females frequently exhibit carcinoma breast, particularly in young subjects below < 40 years. Incriminated females represent with excessively proliferating tumours of advanced stage and enhanced nuclear grade which are immune nonreactive to oestrogen receptors or progesterone receptors and enunciate enhanced proportionate mortality [1,2]. Caucasian women delineate elevated proportionate disease emergence due to obesity, lipid-rich diet or excessive consumption of alcohol. Cigarette smoking is non concurrent to emergence of carcinoma breast. Factors decimating possible occurrence of carcinoma breast are enhanced physical activity, consumption of dietary soy or carotenoids, primigravid state <18 years, oophorectomy <35 years, irradiated ovaries or obese individuals <40 years with an-ovulatory menstrual cycles and decimated premenstrual progesterone levels [1,2]. Additionally, conditions such as proliferative breast disease, ductal carcinoma in situ, concurrent multiple, non-proliferative or proliferative benign breast lesions, endometrial carcinoma, carcinoma of contralateral breast, previous breast tissue sampling, radiation exposure in young women <  30 years as encountered with supra-diaphragmatic radiotherapy adopted for Hodgkin's lymphoma, inherent mammographic density with carcinomas occurring at ≤ 50 years or birth weight > 3 kilograms can contribute to emergence of invasive ductal carcinoma breast [1,2]. Upon gross examination, a firm to hard, poorly circumscribed tumefaction of cartilaginous consistency appears to recede from circumscribing mammary tissue. Scraping of tumour creates a grating sensation [1,2]. Cut surface exhibits chalky- white, linear streaks with focal elastosis extending into enveloping stroma with configuration of "crab like" foci of calcification [1,2].

Enlarged neoplasms demonstrate foci of haemorrhage, necrosis and cystic degeneration. Tumefaction can adhere to chest wall with consequent nipple retraction or dimpling of superimposed cutaneous surface [1,2]. Cytological assessment is achieved with evaluation of features such as cellular pleomorphism, naked tumour nuclei, nuclear magnitude, nuclear periphery, occurrence of nucleoli and mitotic activity. Cytological tumour grade appears concurrent with histological tumour grade [1,2]. Upon microscopy, well differentiated neoplasms depict prominent tubular configurations which are absent in poorly differentiated tumefaction. Low grade neoplasms display focal aggregates of mast cells [1,2]. Tumour cells display cellular and nuclear pleomorphism with nuclear atypia. Neoplastic cells can be singular or configure sheets, nests or cord-like structures. Tumour cells nests are devoid of circumscribing myoepithelial cell layer [1,2]. Stroma is significantly desmoplastic and may entangle obscured aggregates of tumour cells. Tumour necrosis is variable. Focal calcification is observed. Focal elastosis within vascular configurations and ducts engenders grossly visible, chalky-white streaks within the tumour [1,2]. Distinct foci of ductal carcinoma in situ are observed. Perineural invasion ensues. Mitotic figures are prominent. Uncommonly, intraluminal crystalloids can be observed along with focal eosinophilic infiltrate. Melanotic variant exhibits an amalgamation of microscopic features of invasive ductal carcinoma and malignant melanoma [1,2]. Discernible angio-lymphatic invasion commonly appears beyond carcinomatous perimeter and manifests as a tumour cell aggregate with an outline disparate from pervaded tissue space [1,2]. Vascular configurations appear adjacent to neoplastic cell clusters.  Neoplastic cell nests are layered with an endothelial cell layer which is immune reactive to CD31+ or Factor VIII+ [1,2]. Upon ultrastructural examination, foci of glandular differentiation with luminal configuration of microvilli and terminal bars are observed [1,2].

Figure 1: Invasive ductal carcinoma exhibiting ductal articulations of anaplastic ductal epithelial cells with moderate cellular and nuclear pleomorphism and non-conformance with stromal spaces with stromal infiltration.

Figure 2: Invasive ductal carcinoma demonstrating glandular configurations with significant anaplasia, pleomorphism, anisocytosis, hyperchromasia and vesicular nuclei with prominent nucleoli and focal stromal infiltration.

Table 1: TNM classification of Invasive Ductal Carcinoma-Breast [1,2].

Invasive ductal carcinoma is immune reactive to cytokeratin 8/18, cytokeratin 5/6, cytokeratin 19, cytokeratin 7, epithelial membrane antigen (EMA), e-cadherin, oestrogen receptor, milk fat globule, lactalbumin, carcinoembryonic antigen(CEA), B72.3, BCA225, glycogen, mucin, S100 protein, HER2, RCC Ma and CD5 clone 4C7 [3,4]. Immune staining with laminin, type IV collagen and myoepithelial markers frequently depicts a discontinuous or absent basement membrane or myoepithelial cell layer [3,4]. Tumour cells are immune non-reactive to cytokeratin 20,CD10 and myoepithelial marker p63 [3,4]. Invasive ductal carcinoma with focal necrosis may simulate ductal carcinoma in situ [3,4]. Therapeutic strategies are contingent to category, stage and location of neoplasm.  Besides, factors such as age and overall health of incriminated subjects and history of prior disease influence selection of therapeutic strategy [3,4]. Cogent therapy of invasive ductal carcinoma not otherwise specified (NOS) is contingent to tumour magnitude and is defined as                                                       

• Tumefaction below <4 centimetre is subjected to surgical extermination of primary tumour with sampling of axillary lymph nodes. Tumour stage is ascertained following initial surgical intervention [3,4].
• Tumefaction ≥4 centimetres is subjected to modified radical mastectomy along with sampling of axillary lymph nodes [3,4].

Postoperative, adjuvant, combined chemotherapy, radiotherapy, hormonal therapy as with tamoxifen or targeted therapy with agents such as trastuzumab can be beneficially employed [3,4]. Additional surgical intervention is occasionally necessitated in order to achieve comprehensive tumour eradication or excise tumour reoccurrences [3,4].                                                                                           

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3. Parada H, Sun X, Tse CK, Olshan AF, Troester MA. Lifestyle Patterns and Survival Following Breast Cancer in the Carolina Breast Cancer Study. 2019; 30: 83-92.
4. Clark BZ, Onisko A, Assylbekova B, Xin L, Bhargava R, Dabbs DJ. Breast cancer global tumor biomarkers: a quality assurance study of intratumoral heterogeneity. Mod Pathol. 2019; 32: 354-366.