Cutaneous Keratocyst With D2-40 Immunoreactivity in Basal Cell Nevus Syndrome.

ABSTRACT: Although not a diagnostic criterion for basal cell nevus syndrome (BCNS, OMIM#109400), cutaneous cysts, particularly epidermoid cysts, are common in this condition. Cutaneous keratocysts, on the other hand, are extremely rare in general and have been identified in only 5 patients with BCNS. Here, we describe a BCNS patient with a cutaneous keratocyst that demonstrated D2-40 (podoplanin) immunoreactivity, which has been detected in odontogenic keratocysts but not cutaneous keratocysts. This finding suggests that cutaneous keratocysts may be developmentally homologous to odontogenic keratocysts and may behave similarly in terms of invasion and growth pattern.

Verrucous pilar cysts infected with beta human papillomavirus.

Epidermoid cysts with histopathologic features of human papillomavirus (HPV) infection have been previously reported and are commonly termed verrucous cysts. We report a series of eight histopathologically distinct verrucous pilar cysts, distinguished from traditional verrucous epidermoid cysts by trichilemmal keratinization, as well as two verrucous hybrid pilar-epidermoid cysts. These lesions contain characteristic stratified epithelial linings with abrupt transitions to compact eosinophilic keratin, as well as areas of papillomatosis, coarse intracytoplasmic keratohyalin granules, and vacuolar structures suggestive of HPV-induced cytopathic change. HPV-24, a ß genus HPV species, was identified by degenerate polymerase chain reaction in DNA extracted from two of the lesions, and the presence of ß-HPV E4 protein was confirmed by immunohistochemistry. HPV-60, the HPV species most commonly reported in verrucous epidermoid cysts, was not detected. Verrucous pilar cysts represent histopathologically and potentially etiologically distinct lesions which may be underrecognized.

Paediatric orbital conjunctival epithelial cyst with positive asialotransferrin.

Conjunctival orbital cysts are rare; they are typically either conjunctival dermoid or conjunctival epithelial cysts - congenital or acquired (inclusion). We describe the case of a 15-month-old girl presenting with strabismus and proptosis who had a retrobulbar intraconal cystic lesion displacing the optic nerve, with an adjacent middle cranial fossa anomaly. Aspiration of the orbital cyst tested positive for asialotransferrin, raising the suspicion of a direct communication with cerebrospinal fluid (CSF). Subsequent fine cut CT scanning disproved any connection with the intracranial space, and the cyst was excised complete and intact. Histopathology showed a conjunctival epithelial cyst. To our knowledge, this is the first case report in the literature of an asialotransferrin positive pediatric orbital conjunctival epithelial cyst. It is of clinical relevance as it explores the possibility of either a false positive asialotransferrin or potentially a prior developmental communication with the subarachnoid space. These two diagnostic possibilities are discussed.

"Cyst" on the forearm of a 28-year-old female: Case report of a CIC-rearranged sarcoma.

Capicua transcriptional repressor (CIC)-rearranged sarcomas are part of the group of Ewing-like sarcomas or atypical Ewing sarcomas which, thanks to the progress in molecular diagnosis, are being defined by particular genetic abnormalities separating this group into distinct entities with their own particular histological and immunohistochemical features, as well as different survival outcomes. We report the case of a healthy 28-year-old female presenting with a tender lesion on her forearm which after ultrasound examination was clinically favored to represent an infected sebaceous cyst. Hematoxylin-eosin staining showed a lobulated neoplasm within the subcutis composed of poorly differentiated epithelioid to round cells with a small amount of amphophilic cytoplasm. Frequent mitotic figures and tumor necrosis were present. Immunohistochemical studies showed patchy focal CD99 membranous positivity, negative WT1 and TLE1 staining and diffuse nuclear positivity for ETV4 (performed at outside laboratory). FISH analysis showed significant CIC rearrangement enabling a final diagnosis of an undifferentiated small round cell sarcoma harboring the t(4;19)(q35;q13.1) and CIC-DUX4 fusion. This case shows the importance of awareness of this entity as, unlike Ewing sarcoma, these lesions present in the soft tissues rather than bone and may, as in this case, arise in the superficial soft tissues and be submitted to a dermatopathology practice.

Steatocystoma Simplex of the Caruncle: Case Report and Immunohistologic Study.

A yellow cystic lesion of the caruncle in a 23-year-old woman proved to be a solitary steatocystoma, a rare occurrence in that location. While the histopathologic diagnosis was evident from clusters of sebaceous cells within the cyst wall, a panel of immunohistochemical stains further distinguished the lesion from a keratinous cyst. The most useful stains for differentiating the two conditions were carcinoembryonic antigen, epithelial membrane antigen, cytokeratins 17 and 19, and calretinin. Only three previous cases of caruncular steatocystoma simplex have been reported, none of which included immunohistochemical studies. The current findings support the origin of the cyst from the small duct that connects the unilobular sebaceous gland associated with vellus hairs to the follicular canal.

Histopathological Study on the Proposed Pathogenesis of Intratarsal Keratinous Cysts.

PURPOSE: Intratarsal keratinous cysts (IKCs) are a recently described entity that is frequently misdiagnosed clinically as chalazia and mislabeled in the literature as "intratarsal epidermal inclusion cysts" or "epidermoid cysts." It is important to accurately diagnose IKCs and distinguish them from chalazia because IKCs require a complete surgical excision and can exhibit multiple recurrences following curettage. The authors performed a retrospective case series to further elucidate the pathogenesis of IKCs and to determine the diagnostically optimal panel of stains for diagnosis. METHODS: A study group of 8 specimens of IKCs and control specimens of epidermal inclusion cysts were obtained from their pathology laboratories. The authors compared the histological and immunohistochemical profile of IKCs and epidermal inclusion cysts by staining sections from each specimen with hematoxylin and eosin, periodic acid-Schiff, Masson trichrome, cytokeratin 5, cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen. The immunoreactivity data were then analyzed using a 2-tailed Mann-Whitney test, assuming a nonparametric population (p < 0.05 is significant). RESULTS: Histopathologically, IKCs are embedded in the tarsus lined by stratified squamous epithelium with an inner undulating cuticle filled with a compact keratinous-appearing material. The authors demonstrate that IKCs develop progressively from dilated meibomian ducts to the formation of complete cysts with their markers. The most valuable immunochemical stains to diagnose IKC were cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen (p < 0.05 with each). CONCLUSIONS: These findings provide a better understanding of the pathogenesis and the immunohistochemical findings of this relatively new entity allowing for more appropriate diagnosis of IKCs aiming to reduce future complications from their management.

RASopathic comedone-like or cystic lesions induced by vemurafenib: a model of skin lesions similar but not identical to those induced by dioxins MADISH.

BACKGROUND: Patients treated with vemurafenib for metastatic melanoma often develop skin lesions similar to those observed after exposure to dioxin-like compounds. We previously called these lesions MADISH (metabolizing acquired dioxin-induced skin hamartoma) when analysing a case of acute dioxin poisoning. OBJECTIVE: We performed a clinical trial aimed at comparing the skin lesions observed under vemurafenib treatment with MADISH in order to bring to light a possible crosstalk between vemurafenib and dioxin pathways. METHODS: In this case series study, we explored the histological aspect of skin lesions in 10 cases treated with vemurafenib for malignant melanoma. We also analysed the ability of vemurafenib and tyrosine kinase inhibitors to induce dioxin-AhR pathway. RESULTS: All patients had skin lesions diagnosed as 'non-inflammatory acneiform eruption' by dermatologists. These were predominantly facial with notable retroauricular involvement and clinically compatible with chloracne/MADISH when assessed by dioxin expert. Histological analysis showed mostly comedone-like lesions and dermal cysts containing epithelial wall with basal or lateral epithelial projections and lamellar keratinization and alterations of remaining sebaceous glands. The expression of CYP1A1, a gene highly induced following dioxin exposure, was not observed in these lesions. Vemurafenib and the tyrosine kinase inhibitors erlotinib and gefitinib did not induce CYP1A1 activity. DISCUSSION: Although the skin lesions under vemurafenib treatment were morphologically similar to MADISH, the absence of CYP1A1 expression in dermal cysts of patients and the absence of CYP1A1 activation by vemurafenib led us consider that these skin lesions were different from true MADISH and not mediated by a crosstalk of AhR signalling, but rather to a hyperactivation of PI3K-Akt pathway as a consequence of vemurafenib treatment. A strong expression of CYP1A1 in the epithelial wall of dermal cysts must be required, parallel to the morphology of the lesions, to make the diagnosis of MADISH, the hallmark of an exposure to dioxin-like/chloracnegen compounds.

Classification of cysts with follicular germinative differentiation.

BACKGROUND: Cysts are very common in the routine of dermatopathology but follicular germinative (trichoblastic) differentiation in cysts is seen rarely. The presence of follicular germinative differentiation in a cyst alerts to consider the possibility of a basal cell carcinoma (BCC) arising in a cyst. METHODS: Five cystic lesions with zones of follicular germinative differentiation were collected. Hematoxylin and eosin sections were reassessed for architecture, types of follicular differentiation and stromal characteristics; immunohistochemical studies with Ber-EP4 were analyzed. Articles about follicular germinative differentiation in cystic lesions were reviewed. RESULTS: Cystic lesions with follicular germinative differentiation have been described in the literature under various names including trichoblastic infundibular cyst, cystic trichoblastoma, cystic panfolliculoma (CPF), dermoid cyst with basaloid proliferations, folliculosebaceous cystic hamartoma and BCC occurring in infundibular cysts. The lesions presented by us could be classified as three cystic trichoblastomas, one CPF and one cystic hamartoma with follicular germinative differentiation. CONCLUSIONS: Histopathologically, cystic trichoblastomas can be separated from CPFs. Some lesions defy classification and may be regarded as cystic follicular hamartomas. The presence of follicular papillae and bulb-like structures, advanced follicular differentiation like that of inner and outer root sheath exclude the differential diagnosis of BCC arising in a cyst.

Unusual Eyelid Dermal Keratinous Cysts of Pilosebaceous Origin.

PURPOSE: To describe 2 types of previously unrecognized dermal keratinous cysts of the eyelids-2 single sebaceous duct cysts derived from the glands of Zeis and 2 cases of multiple eruptive vellus hair cysts, both types associated with the pilosebaceous apparatus. METHODS: Clinical records and paraffin sections subjected to hematoxylin and eosin and acid-fast staining were critically reviewed from each case, and additional sections were immunoreacted for cytokeratins (CKs) 7, 14, and 17. RESULTS: Two patients had a slowly enlarging solitary sebaceous duct keratinous cyst at the eyelid margin where the glands of Zeis are located. The squamous cell lining displayed a corrugated squamous membrane manifesting an eosinophilic, refractile, surface cuticle. Either a sebaceous gland or a hair was proximate to the cyst. The squamous lining was CK7, CK14, and CK17. Two other patients developed over 2 and 10 years a different condition consisting of unilateral or bilateral clusters, respectively, of small papules of the upper eyelids. These were lined by keratinizing squamous epithelium without a cuticular membrane. Numerous small vellus hairs along with keratin in the lumens were discovered with acid-fast staining. The epithelium was also CK7, CK14, and CK17. CONCLUSIONS: Histopathologic and immunohistochemical studies can separate these 2 disparate new eyelid entities from the more common keratinous epidermoid cyst of the surface epidermis or the upper hair follicle (CK7, CK14, and CK17). Simple local excision of the anterior lamella of the eyelid is appropriate for the sebaceous duct keratinous cysts of Zeis, but the multiple vellus hair cysts are comparatively refractory to treatment. Both superficial types of cysts are totally unrelated to the deeper Meibomian keratinous cyst, which is not associated with a hair structure and is situated in the tarsus rather than the dermis of the eyelids.

Aryl Hydrocarbon Receptor Activation in Acne Vulgaris Skin: A Case Series from the Region of Naples, Italy.

BACKGROUND: Dioxins are persistent organic pollutants present in the environment. They exert their biological effects by binding to an intracellular receptor, the aryl hydrocarbon receptor (AhR). Activation of AhR leads to the induction of cytochrome p450 1A1 (CYP1A1). Expression of CYP1A1 in human skin is a key marker for AhR activation, and it may induce comedogenesis resulting in acne-like lesions known as chloracne/metabolising acquired dioxin-induced skin hamartomas (MADISH). The contribution of this pathway in patients seen in a busy acne clinic is unknown. MATERIALS AND METHODS: We explored the expression of CYP1A1 by immunohistochemistry in the acne lesions of 16 patients living in the region of Naples, Italy, where epidemiological studies have suggested a possibly increased exposure to environmental dioxins. A composite score to outline potential components of the chloracne/MADISH histological pattern was used. RESULTS: CYP1A1 expression was observed in 11 lesions (69%) and was distributed in sebaceous glands, follicular epithelium, cystic wall and endothelial cells. The histological score for chloracne/MADISH was 'likely' in 3 cases and 'possible' in 11 cases. Compared to current data on CYP1A1 expression in the skin of 67 patients with proven exposure to AhR agonists, these data indicate a high incidence of AhR activation in this series. CONCLUSION: This is the first study analysing AhR activation in skin in a series of patients from a hospital-based acne clinic. It provides information for future controlled prospective studies. The significance of CYP1A1 expression in terms of AhR ligand exposure is discussed.

Clinicopathological features and expression of four keratins (K10, K14, K17 and K19) in six cases of eruptive vellus hair cysts.

Six cases of eruptive vellus hair cysts (EVHC) were evaluated for histopathology and the immunohistochemical profile of Ki-67 and four keratins (K10, K14, K17 and K19). The pathological hallmark of EVHC was the existence of vellus hair shafts within the cystic cavity, but atypical pathological changes included two or three cysts and a foreign-body granuloma in three cases. Our results demonstrate that atypical pathological changes are not uncommon in EVHC, and indicate that based on keratin expression, it is likely that EVHC is derived from the infrainfundibulum and sebaceous duct.

Histopathological, histogenetic, and immunohistochemical analysis of epidermoid cyst of spleen.

Splenic cysts are encountered not uncommonly, but large cysts occupying a significant portion of the spleen are extremely rare. We report a case of a young female patient presenting with a large epidermoid cyst involving the majority of the spleen. The patient was involved in a motor vehicle accident during which she sustained multiple rib fractures and traumatic internal organ injuries. She subsequently underwent exploratory laparotomy and splenectomy for grade III splenic lacerations. Incidentally, a 13.3 cm in greatest dimension splenic cyst replacing the majority of the splenic parenchyma was identified. Grossly, the inner lining of cyst was gray-white, smooth, and glistening. Histologically, the thick fibrous cyst wall was composed of stratified squamous epithelium, scattered foci of which were denuded. A panel of properly-controlled immunohistochemical stains was performed and showed the squamous epithelium to be strongly and diffusely immunoreactive with carcinoembryonic antigen (CEA), CA 19-9, and cytokeratin 5/6, focally immunoreactive with HBME-1, and negative for calretinin. The histomorphological features and immunohistochemical staining pattern were consistent with a diagnosis of an epidermoid cyst of the spleen.

Cutaneous ciliated cyst on the finger: a cutaneous mullerian cyst.

As previously recognized by various authors, "cutaneous ciliated cyst" is a confusing term. Typically, the term refers to rare cystic lesions, commonly found on the lower limbs of women in their reproductive years. To date, 40 cases diagnosed as "cutaneous ciliated cyst" have been reported in the literature. Histologically, the cysts are composed of a simple layer of ciliated columnar cells along with nonciliated columnar cells, cuboidal cells, and round "peg-like" cells, resembling fallopian tube epithelium. This histology has been described in cysts found in males and females and in locations other than the lower limbs. Controversy has thus arisen over the etiology of these lesions, with some believing that the cysts arise from heterotopic Mullerian rests and others advocating for ciliated metaplasia of eccrine glands. We herein describe the first case of cutaneous ciliated cyst of Mullerian origin occurring on the dorsal thumb of a 16-year-old female. A review of literature shows that 2 groups of cysts are covered under the umbrella term "cutaneous ciliated cysts." We thus propose the abandonment of the confusing term "cutaneous ciliated cyst" and the adoption of "cutaneous Mullerian cysts" for estrogen receptor/progesterone receptor-positive lesions resembling simple fallopian tube epithelium and "Cutaneous ciliated eccrine cyst" for estrogen receptor/progesterone receptor-negative lesions usually occurring in males, which are immunohistochemically compatible with an eccrine origin.

Multiple intratarsal keratinous cysts of the eyelid.

Intratarsal keratinous cysts are uncommonly reported entities that originate within the tarsal plate. Previously reported cysts have always been solitary, whether primary or recurrent. The authors present an unusual case of a 50-year-old man with 11 intratarsal keratinous cysts on a single eyelid. Complete excision of all the cysts was curative for at least 2 months.

Epidermoid cyst occurring within an intrapancreatic accessory spleen. A case report and review of the literature.

CONTEXT: Epidermoid cysts occurring within intrapancreatic accessory spleens are exceptionally rare entities, with only 21 previously reported cases. Their clinical presentation prior to pathologic assessment can raise concern for possible malignancy; however, they behave in a benign fashion. CASE REPORT: A 62-year-old male presented with complaints of abdominal pain. Imaging revealed left-sided retroperitoneal mass and surgical exploration was recommended. Surgery revealed a cystic cavity containing necrotic debris originating from the tail of the pancreas. Microscopy was consistent with an epidermoid cyst arising within an intrapancreatic accessory spleen with positive immunoperoxidase staining for CEA. CONCLUSION: Epidermoid cysts occurring within intrapancreatic accessory spleens can mimic a malignant process both clinically and radiographically. Surgery with pathologic assessment is the only reliable means of diagnosis. While they are a very rare entity, it is an important component of a complete differential diagnosis for a patient presenting with a pancreatic tail mass.

Intratarsal keratinous cysts of the meibomian gland (a sebaceous duct cyst): report of 2 cases.

Intratarsal keratinous cyst of the meibomian gland is a recently described entity that recurs if not completely excised. Herein, we report 2 cases and discuss their diagnosis and management: (1) A 57-year-old man with a recurrent mass of the upper eyelid treated with incision and drainage as a chalazion for more than 5 years and (2) An 85-year-old man presented with a slow growing nodule of the upper eyelid. Exploration via the eyelid crease approach revealed cysts fixed to the tarsus that were completely excised with a portion of the anterior tarsus. Histologically, these cysts exhibited a keratinizing squamous epithelium without a granular layer (trichilemmal keratinization), were lined by an eosinophilic undulating cuticle, contain string-like keratin debris, and had a fibrous wall without sebaceous lobules. All epithelial components strongly expressed high-molecular weight keratins, whereas the lining, cuticle, and keratin contents strongly expressed carcinoembryonic antigen. No recurrence has occurred 7 and 12 months postoperatively. The location and clinicopathologic findings of intratarsal keratinous cysts distinguish it from sebaceous tumors, steatocystoma simplex, epidermoid cyst, and dermoid cyst. However, like steatocystomas, intratarsal keratinous cysts exhibit a sebaceous duct phenotype. The anterior lid crease approach with partial tarsectomy seems to be an effective treatment.

Comparative immunohistochemical analyses on the modes of cell death/keratinization in epidermal cyst, trichilemmal cyst, and pilomatricoma.

Keratinization is a kind of cell death called terminal differentiation and includes various patterns such as epidermal keratinization (EK), trichilemmal keratinization (TK), and shadow cell differentiation (SCD), whereas these have not been comparatively investigated from a standpoint of cell death. In the present study, surgically extirpated specimens of epidermal cyst, trichilemmal cyst, and pilomatricoma (10 cases in each) were subjected to immunohistochemistry for single-strand DNA (ssDNA), gamma-H2AX, cleaved caspase-3, cleaved lamin A, caspase-14, and CD138 to compare the modes of cell death and keratinization pattern. Transitional cells in pilomatricoma were immunoreactive, although not in whole part, for ssDNA and gamma-H2AX, and negative for cleaved caspase-3 and cleaved lamin A. Epidermal and trichilemmal cyst were negative for these 4 markers, except for ssDNA or cleaved lamin A in a small number of parakeratotic cells in a few cases. The keratinizing component showed caspase-14(+)/CD138(-) in epidermal cyst, caspase-14(-)/CD138(+) in trichilemmal cyst, and caspase-14(-)/CD138(-) in pilomatricoma. These results indicate that EK, TK, and SCD have a common property of apoptosis-like programmed cell death without caspase-3 activation or nuclear fragmentation. Meanwhile, they show different characteristics one another as follows: (A), DNA double-strand breaks occur in the transitional cells of SCD but not in EK/TK; and (B), EK, TK, and SCD can be distinguished by expression pattern of caspase-14 and CD138 in the keratinizing component.

Cutaneous ciliated cyst: a case report with focus on mullerian heterotopia and comparison with eccrine sweat glands.

Cutaneous ciliated cyst is an exceedingly rare, benign lesion most commonly found in the dermis or subcutis of the lower extremities of young female patients in their second and third decades. The pathogenesis of the cyst is unknown. We report a cutaneous ciliated cyst in the lower extremity of a 13-year-old female patient. On histologic examination, clusters of eccrine sweat glands were observed adjacent to the cyst. Upon comparison of the immunohistochemical profile of the cutaneous ciliated cyst and the eccrine sweat glands, they appeared almost completely unrelated. The histologic, immunohistochemical, and ultrastructural findings of this case and the literature provide evidence in favor of the Mullerian heterotopia theory.