Melissa Alexander

Primary anorectal mucosal melanoma detected by anorectal cytology

The detection of primary anorectal melanoma on anal cytology is a rare and challenging diagnosis. We report a case where anorectal cytology showed isolated malignant cells with oval nuclei, prominent nucleoli, and elongated wispy cytoplasmic projections. There was no evidence of squamous dysplasia or melanin pigment identified. To the best of our knowledge, this is the first reported case of a primary anorectal melanoma detected in anorectal cytology. Detection of malignancies other than squamous cell carcinoma can be seen on anorectal cytology and should be considered when there is no evidence of anal intraepithelial neoplasia. Diagn. Cytopathol. 2017;45:452–455.

Inflammatory myofibroblastic tumour of the testis with confirmed anaplastic lymphoma kinase gene rearrangement.

Sir: Inflammatory myofibroblastic tumour (IMT), previously referred to as ‘inflammatory pseudotumour’, is a rare spindle-cell neoplasm that typically affects young patients. The lesion has a tendency to recur following resection, and has a low metastatic potential. Initially described in the lung, IMTs have since been recognized in a wide variety of anatomical sites. In the male reproductive organs, IMT is particularly rare, usually involving the paratestis. To our knowledge, only three cases of an intratesticular IMT have been described, all of which were either not associated with or evaluated for anaplastic lymphoma kinase (ALK) reactivity. We describe the first case of an ALK-positive IMT within the testicular parenchyma with the characteristic ALK rearrangement demonstrated by the use of both immunohistochemistry and fluorescence in-situ hybridization (FISH). A 22-year-old male presented to our institution with a right testicular swelling. He had no significant prior medical history. Ultrasonography revealed two hypoechoic echogenic lesions that were considered to be solid in nature. Magnetic resonance imaging demonstrated two solid enhancing rounded homogeneous intratesticular lesions. A right-sided orchiectomy was performed. The specimen was a 48-g, 50 9 30 9 30-mm testis with an attached epididymis and spermatic cord. The testis was bisected along its long axis, and this revealed two discrete tan–yellow nodules that measured 10 mm and 9 mm each. The lesions were 1 mm apart. The remaining

Medallion-like dermal dendrocytoma

Medallion-like dermal dendrocytoma is a benign cutaneous neoplasm that mimics dermatofibrosarcoma protuberans histologically. The distinction between these two entities is critical to prevent unnecessary wide excisions. Herein we describe an acquired MLDD in a 55-year-old female.

Multifocal Invasive Ductal Cancer: Distinguishing Independent Tumor Foci From Multiple Satellites

Patients with multifocal breast cancers (MBCs) have a poorer prognosis than patients with unifocal breast cancers. Studies have attributed this to tumor size underestimation in MBC. An alternative hypothesis is that some MBCs behave in a fashion analogous to the “satellite” and “in-transit metastasis” observed in melanoma and, thereby, are more clinically aggressive. We identified 79 cases of MBC, which we classified into 2 groups: study cases defined as ≥2 morphologically similar tumor foci with ≥1 focus without in situ carcinoma (n = 21); and a control group defined as ≥2 morphologically similar or dissimilar foci with associated in situ carcinoma in all foci (n = 58). The odds of being a study case is 1.86 (95% confidence interval [CI] 1.26-2.74) times greater per unit increase in number of tumor foci (median of 4 tumor foci; P = .002). Study cases were 73.33 (95% CI = 8.91-603.16) times more likely to have lymphovascular invasion (LVI) and 14.72 (95% CI = 4.37-49.61) times more likely to have nodal metastases. Grade I/II tumors were 0.20 (95% CI = 0.07-0.59) times less likely to be study cases. There was a significant positive interaction (P < 0.001) indicated by the relationship of LVI status and nodal status with the study case and control group. We conclude that there is a subset of MBC that presents with more numerous tumor foci and a higher rate of nodal metastasis. The aggressive behavior of these cases may be attributed to their proclivity for LVI.

Can p40 (Polyclonal) Replace p63 (Clone 4A4) in the Cytologic Diagnosis of Pulmonary Non–Small Cell Carcinoma?

Objectives Differentiating squamous cell carcinoma from adenocarcinoma (ACA) in cytology specimens can be challenging. Recent literature showed p40 had higher specificity than p63 for this purpose. Methods We identified 190 cytology cases with p40 (polyclonal) and p63 (monoclonal clone 4A4) immunohistochemistry, including specimens from fine-needle aspirations (FNAs) and effusions. Results ACAs of lung origin stained for p40 and p63 in 21% and 20% of cases, respectively, regardless of specimen site. Among lung FNAs of primary pulmonary ACAs (n = 42), 14% were positive for p40 and 24% were positive for p63. Of the 20 pulmonary ACAs in effusions, more cases showed p40 positivity (40%) compared with FNAs, whereas p63 were positive in 15%. Among metastatic ACAs from other sites (n = 14), more cases were positive for p40 than p63. Conclusions Polyclonal p40 yields a level of false positivity in ACAs similar to p63, which is highest in effusions and is not limited to lung origin.

Hyperactivated mTOR and JAK2/STAT3 pathways: Crucial molecular drivers and potential therapeutic targets of inflammatory breast cancer (IBC).

60 Background: IBC is an aggressive form of breast cancer with poor prognosis. Combined multi-modality Rx results in a 5 year OS of 30-50%, underscoring the unmet need for targeted Rx. Our preclinical research in cell lines and xenografts identifies a role for activated PI3K/mTOR pathway in IBC. IBC cells express IL-6 and IL-8 and recruit tumor activated macrophages (TAMs) that further induce IL-6, IL-8 and activate the JAK2/STAT3 pathway. We investigated the independent and combined activity of these pathways in IBC tissues. METHODS Archived tissues of 42 IBC pts and 13 controls (nl breast) were analyzed using IHC and scored by 3 independent pathologists. Results defined as: 0, 1+ = neg; 2+ = pos for activated mTOR (P-S6) and 0 = neg; 1+, 2+ = pos for activated nuclear JAK2/STAT3 (P-JAK2; P-STAT3), cytokine (IL-6), macrophage (mØ) infiltration (CD68) and TAM (CD163). Proportions of IBC cases with pos expression were compared with controls (Fishers exact tests). Clinical and survival data were obtained. RESULTS Median age at diagnosis: 46 yrs (31-62) in early-stage IBC [EIBC] (n=37) and 41 yrs (29-57) in pts with de novo metastatic IBC [MIBC] (n=5). In EIBC, 19/36: HER2+ (1 unk); 8/19: ER+/HER2+; 8/36: ER-/HER2-. In MIBC, all were ER- (1 unk) and 3/4 were HER2+ (1 unk). 88% Rx with neoadjuvant and/or adjuvant anthracycline and taxane w/o adjuvant trastuzumab. 24 pts died (5/5 MIBC). Median OS: 86 mo (95% CI lower 48 mo) for EIBC & 41 mo (95% CI 8-81 mo) for MIBC. Median RFS: 18 mo (95% CI 18-79 mo) for 23 pts (13 NED; 1 unk). All controls: neg for P-S6, JAK2, STAT3 and TAMs and 92% neg for mØ and IL-6. Proportion of IBC with pos expression when compared to controls listed in table (p <0.0001). Of 31 pts with complete biomarker data who were PS6+, 97% had activated JAK2, 58% had activated STAT3, 80% had strong mØ and TAM infiltration and 97% were IL6+. CONCLUSIONS This is the first study that validates preclinical findings and shows a strong association between mTOR, cytokines, TAMs and JAK/STAT pathways in most IBC pt tissues. Findings suggest a key role for dual blockade of mTOR and JAK/STAT pathways in phase I trials. [Table: see text].