LETTERS
Primary Cutaneous Endocrine Mucin– Producing Sweat Gland Carcinoma Co-occurring Simultaneously With Low-Grade Ductal Mucinous Breast Cancer: A Clinicopathologic Conundrum To the Editor: Endocrine mucin–producing sweat gland carcinoma (EMPSGC) is a rare, underreported, low-grade cutaneous malignancy affecting elderly patients with a median age of 70 years, and a significant predilection for females.1 The tumor typically occurs on the eyelids or periorbital skin1 and manifests clinically as a nondescript slowly enlarging flesh-colored nodule, plaque, or swelling.1,2 Histologically, it is characterized by low-grade morphological features, production of mucin, and expression of neuroendocrine markers.1,3 The tumor is clinically indolent and cured by local excision; however, local recurrences may occur.4,5 The coexistence of EMPSGC and low-grade ductal mucinous breast carcinoma has not been hitherto reported. A 75-year-old white female with no oncologic history presented to her dermatologist with a small, asymptomatic, nonulcerated, skin-colored nodule located on the skin adjacent to her left lower eyelid, and slowly enlarging over a period of approximately 3 years. The initial pathologic interpretation at an outside institution was of poorly differentiated carcinoma, and a metastasis was favored. The patient requested a second opinion. Our microscopic examination of the excisional biopsy revealed The authors declare no conflicts of interest.
TO THE
EDITOR
a well-demarcated dermal tumor composed of solid and focal cribriform nests and strands separated by thin fibrous septa. The nests consisted of medium sized round to oval cells with relatively monomorphic nuclei and amphophilic cytoplasm embedded in a mucinous stroma (Figs. 1A–C). Occasional intracellular mucin and hyalinized fibrovascular cores were noted. The tumor cells were positive for cytokeratin AE1/AE3, estrogen and progesterone receptors, GCDFP15, cytokeratin 7, and patchy for synaptophysin (Figs. 1E, F), whereas negative for cytokeratin 20, CDX-2, and S100. There was no immunohistochemical evidence of Her2/neu overexpression. Ki-67 proliferation index ranged from 5% to
10%. P63 and calponin revealed a layer of myoepithelial cells at the periphery of some tumor nests, indicating an in situ component (Fig. 1D). Based on morphological and immunohistochemical features, the tumor was reclassified as a primary cutaneous EMPSGC. Although a primary cutaneous malignancy was favored, given the demographics of the patient, screening for breast cancer was suggested. Subsequent imaging showed a left breast mass that was biopsied and excised to reveal a 2.8 cm welldifferentiated invasive ductal mucinous carcinoma (Nottingham grade 1) with a focal in situ component (Figs 2A–C). The tumor showed a diffuse expression of estrogen and progesterone receptors,
FIGURE 1. EMPSGC of the periorbital skin: (A) Low power view demonstrates a welldemarcated dermal tumor with lobular architecture. Mucin pools with floating epithelial strand, equivalent to invasive mucinous carcinoma, are present (an arrow) (H&E, ·20). B, Medium power magnification shows predominantly solid tumor nests and conspicuous mucinous stroma (H&E, ·100). C, Tumor is composed of cytologically bland and neuroendocrine-appearing cells. Focal cribriform arrangement is seen (H&E, ·400). D, P63 immunostain highlights a layer of myoepithelial cell at the periphery of some nests demarcating an in situ component. Calponin parallels this expression pattern (not shown). E, Tumor cells are immunoreactive for synaptophysin, and (F) display a strong and diffuse nuclear expression of estrogen receptor.
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Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Letters to the Editor
Am J Dermatopathol Volume 37, Number 5, May 2015
FIGURE 2. Left breast low-grade mucinous carcinoma: (A) Low magnification of a core biopsy shows invasive mucinous carcinoma (H&E, ·100). B, High power view demonstrates low-grade nuclei and amphophilic cytoplasm. This malignancy morphologically closely resembles the cutaneous tumor (H&E, ·400). C, P63 immunostain marks myoepithelial cell delineating an in situ component. D, Neuroendocrine differentiation is substantiated by tumor immunoreactivity for synaptophysin.
and a patchy expression of synaptophysin (Fig. 2D). Her2/neu was not overexpressed. Two left axillary sentinel lymph nodes were negative for metastatic carcinoma. Extensive clinical evaluation revealed no evidence of a metastatic disease. Many primary cutaneous neoplasms parallel morphological and immunohistochemical features of breast tumors, reflecting similar embryological origin of sweat and mammary glands.3 EMPSGC is a cutaneous analog of and is histologically indistinguishable from mammary solid papillary carcinoma.1,3 Both tumors are commonly seen in continuity with invasive mucinous carcinoma and hence may represent a precursor stage thereof.1,5 The co-occurrence of EMPSGC and breast carcinoma is not unexpected because the latter is a relatively common malignancy6 and may fortuitously coincide with other tumors.7 Moreover, both conditions typically affect elderly females. An accurate distinction of a primary skin tumor from a metastasis is of paramount clinical importance. However, the definitive distinction of a cutaneous adnexal tumor with mucinous features from a metastatic visceral mucinous carcinoma frequently poses a diagnostic challenge. In our patient, the clinical context provided some clues aiding in resolving the diagnostic dilemma. Lowgrade mucinous breast carcinomas have
426
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a low risk of progression and distant dissemination, especially in the context of negative sentinel lymph nodes biopsy.8 Additionally, the presence of an isolated cutaneous metastasis of few years duration with no evidence of other metastasis would be highly improbable and therefore incompatible with a metastatic etiology of the skin tumor. In our opinion, however, the ultimate evidence of the separate origin of both tumors came from a histopathology demonstrating an in situ component of EMPSGC denoting a primary cutaneous proliferation.3,9 This was accomplished even before the breast tumor was biopsied and facilitated by using immunohistochemical markers to highlight a layer of myoepithelial cells surrounding tumor nests.1,9,10 In summary, we describe a case of low-grade mucinous carcinoma of the breast detected in a patient previously diagnosed with primary cutaneous EMPSGC, a hitherto unreported cooccurrence. The correct diagnosis of tumors representing separate malignancies was made after careful pathology evaluation and clinicopathologic correlation. The histologic examination played a pivotal role in this process. The in situ component confirming primary cutaneous tumor has been evidenced by immunohistochemical identification of myoepithelial cells. EMPSGC has to be included
in the differential diagnosis of adnexal skin tumors detected in patients with mucinous visceral malignancies to avoid a potentially disastrous misdiagnosis of metastatic carcinoma. Jaroslaw Jedrych, Miroslawa Jones, Raja Seethala, Jonhan Ho,
MD* MD† MD† MD*
Departments of *Dermatology, and †Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
REFERENCES 1. Zembowicz A, Garcia CF, Tannous ZS, et al. Endocrine mucin-producing sweat gland carcinoma: twelve new cases suggest that it is a precursor of some invasive mucinous carcinomas. Am J Surg Pathol. 2005;29:1330–1339. 2. Mehta S, Thiagalingam S, Zembowicz A, et al. Endocrine mucin-producing sweat gland carcinoma of the eyelid. Ophthal Plast Reconstr Surg. 2008;24:164–165. doi: 10.1097/ IOP.0b013e3181659c96. 3. Flieder A, Koerner FC, Pilch BZ, et al. Endocrine mucin-producing sweat gland carcinoma: a cutaneous neoplasm analogous to solid papillary carcinoma of breast. Am J Surg Pathol. 1997;21:1501–1506. 4. Koike T, Mikami T, Maegawa J, et al. Recurrent endocrine mucin-producing sweat gland carcinoma in the eyelid. Australas J Dermatol. 2013;54:e46–e49. 5. Hoguet A, Warrow D, Milite J, et al. Mucinproducing sweat gland carcinoma of the eyelid: diagnostic and prognostic considerations. Am J Ophthalmol. 2013;155:585–592 e2.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 5, May 2015
6. McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ. 2000;321: 624–628. 7. Andersson I, Aspegren K, Janzon L, et al. Mammographic screening and mortality from breast cancer: the Malmo mammographic screening trial. BMJ. 1988;297: 943–948. 8. Diab SG, Clark GM, Osborne CK, et al. Tumor characteristics and clinical outcome of tubular and mucinous breast carcinomas. J Clin Oncol. 1999;17:1442–1448. 9. Kazakov DV, Suster S, LeBoit PE, et al. Mucinous carcinoma of the skin, primary, and secondary: a clinicopathologic study of 63 cases with emphasis on the morphologic spectrum of primary cutaneous forms: homologies with mucinous lesions in the breast. The Am J Surg Pathol. 2005;29: 764–782. 10. Dhaliwal CA, Torgersen A, Ross JJ, et al. Endocrine mucin-producing sweat gland carcinoma: report of two cases of an underrecognized malignant neoplasm and review of the literature. Am J Dermatopathol. 2013; 35:117–124.
Perivascular Basophilic Rim as a Histopathological Clue of Cutaneous Pseudomona aeruginosa Sepsis To the Editor: Ecthyma gangrenosum represents a formidable skin sign of the potentially life-threatening systemic infection caused by Pseudomonas aeruginosa (PA). Early diagnosis is vital in the management of PA sepsis. Clinical and histological skin manifestations of ecthyma gangrenosum occur with some variation of appearance, depending on the course of the lesion when it was first observed.1 We describe an immunosuppressed patient with multiple cutaneous lesions by PA sepsis. A 74-year-old man, a known case of large B-cell lymphoma stage IV-A, presented with fever, weakness, and fatigue 8 days after the third chemotherapy cycle. Physical examination revealed a pale and cachectic appearance. Oral temperature was 38.9°C. Thorax x-ray showed condensation in the right upper lobe. Blood analysis The authors declare no conflicts of interest.
Letters to the Editor
FIGURE 1. Intraepidermal vesicles and bullae, blood extravasation, and perivascular basophilic rings (H&E ·100). Detail of perivenular basophilic ring (bottom left corner) (H&E ·200).
revealed pancytopenia. The following day, physical examination showed 9 small, sparse, purplish patches in the patient’s trunk. Blood, urine, stool, and skin cultures were obtained. A skin biopsy was performed and revealed epidermal necrosis with vesicles and bullae, extensive extravasation of red blood cells into the dermis, and some superficial skin vessels with fibrinoid necrosis, but without inflammatory infiltration or thrombi. A perivascular basophilic rim was noted (Fig. 1). Gram stain revealed gram-negative bacilli concentrated at the adventitia of venules and scattered among the collagen
bundles in the dermis and the panniculus adiposus (Fig. 2). Blood and cutaneous cultures grew PA, sensitive to meropenem. The patient received intensive antibiotic treatment and supportive measures, but he developed multiple organ dysfunction syndrome and died 2 days later. The definition of septic vasculopathy is confusing. Histopathologically speaking, septic vasculitis is a thrombo-occlusive vasculopathy with variable morphology. Recently, septic vasculopathy has been defined as the occurrence of the following vascular changes: vessel wall neutrophil infiltration, edema, leukocytoclasis,
FIGURE 2. Gram-negative bacilli around the vessels (gram ·100). In the bottom left corner, gram-negative bacilli sparse the intima (arrows) (gram ·400).
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.amjdermatopathology.com |
427
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Primary Cutaneous Endocrine Mucin– Producing Sweat Gland Carcinoma Co-occurring Simultaneously With Low-Grade Ductal Mucinous Breast Cancer: A Clinicopathologic Conundrum To the Editor: Endocrine mucin–producing sweat gland carcinoma (EMPSGC) is a rare, underreported, low-grade cutaneous malignancy affecting elderly patients with a median age of 70 years, and a significant predilection for females.1 The tumor typically occurs on the eyelids or periorbital skin1 and manifests clinically as a nondescript slowly enlarging flesh-colored nodule, plaque, or swelling.1,2 Histologically, it is characterized by low-grade morphological features, production of mucin, and expression of neuroendocrine markers.1,3 The tumor is clinically indolent and cured by local excision; however, local recurrences may occur.4,5 The coexistence of EMPSGC and low-grade ductal mucinous breast carcinoma has not been hitherto reported. A 75-year-old white female with no oncologic history presented to her dermatologist with a small, asymptomatic, nonulcerated, skin-colored nodule located on the skin adjacent to her left lower eyelid, and slowly enlarging over a period of approximately 3 years. The initial pathologic interpretation at an outside institution was of poorly differentiated carcinoma, and a metastasis was favored. The patient requested a second opinion. Our microscopic examination of the excisional biopsy revealed The authors declare no conflicts of interest.
TO THE
EDITOR
a well-demarcated dermal tumor composed of solid and focal cribriform nests and strands separated by thin fibrous septa. The nests consisted of medium sized round to oval cells with relatively monomorphic nuclei and amphophilic cytoplasm embedded in a mucinous stroma (Figs. 1A–C). Occasional intracellular mucin and hyalinized fibrovascular cores were noted. The tumor cells were positive for cytokeratin AE1/AE3, estrogen and progesterone receptors, GCDFP15, cytokeratin 7, and patchy for synaptophysin (Figs. 1E, F), whereas negative for cytokeratin 20, CDX-2, and S100. There was no immunohistochemical evidence of Her2/neu overexpression. Ki-67 proliferation index ranged from 5% to
10%. P63 and calponin revealed a layer of myoepithelial cells at the periphery of some tumor nests, indicating an in situ component (Fig. 1D). Based on morphological and immunohistochemical features, the tumor was reclassified as a primary cutaneous EMPSGC. Although a primary cutaneous malignancy was favored, given the demographics of the patient, screening for breast cancer was suggested. Subsequent imaging showed a left breast mass that was biopsied and excised to reveal a 2.8 cm welldifferentiated invasive ductal mucinous carcinoma (Nottingham grade 1) with a focal in situ component (Figs 2A–C). The tumor showed a diffuse expression of estrogen and progesterone receptors,
FIGURE 1. EMPSGC of the periorbital skin: (A) Low power view demonstrates a welldemarcated dermal tumor with lobular architecture. Mucin pools with floating epithelial strand, equivalent to invasive mucinous carcinoma, are present (an arrow) (H&E, ·20). B, Medium power magnification shows predominantly solid tumor nests and conspicuous mucinous stroma (H&E, ·100). C, Tumor is composed of cytologically bland and neuroendocrine-appearing cells. Focal cribriform arrangement is seen (H&E, ·400). D, P63 immunostain highlights a layer of myoepithelial cell at the periphery of some nests demarcating an in situ component. Calponin parallels this expression pattern (not shown). E, Tumor cells are immunoreactive for synaptophysin, and (F) display a strong and diffuse nuclear expression of estrogen receptor.
Am J Dermatopathol Volume 37, Number 5, May 2015
www.amjdermatopathology.com |
425
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Letters to the Editor
Am J Dermatopathol Volume 37, Number 5, May 2015
FIGURE 2. Left breast low-grade mucinous carcinoma: (A) Low magnification of a core biopsy shows invasive mucinous carcinoma (H&E, ·100). B, High power view demonstrates low-grade nuclei and amphophilic cytoplasm. This malignancy morphologically closely resembles the cutaneous tumor (H&E, ·400). C, P63 immunostain marks myoepithelial cell delineating an in situ component. D, Neuroendocrine differentiation is substantiated by tumor immunoreactivity for synaptophysin.
and a patchy expression of synaptophysin (Fig. 2D). Her2/neu was not overexpressed. Two left axillary sentinel lymph nodes were negative for metastatic carcinoma. Extensive clinical evaluation revealed no evidence of a metastatic disease. Many primary cutaneous neoplasms parallel morphological and immunohistochemical features of breast tumors, reflecting similar embryological origin of sweat and mammary glands.3 EMPSGC is a cutaneous analog of and is histologically indistinguishable from mammary solid papillary carcinoma.1,3 Both tumors are commonly seen in continuity with invasive mucinous carcinoma and hence may represent a precursor stage thereof.1,5 The co-occurrence of EMPSGC and breast carcinoma is not unexpected because the latter is a relatively common malignancy6 and may fortuitously coincide with other tumors.7 Moreover, both conditions typically affect elderly females. An accurate distinction of a primary skin tumor from a metastasis is of paramount clinical importance. However, the definitive distinction of a cutaneous adnexal tumor with mucinous features from a metastatic visceral mucinous carcinoma frequently poses a diagnostic challenge. In our patient, the clinical context provided some clues aiding in resolving the diagnostic dilemma. Lowgrade mucinous breast carcinomas have
426
| www.amjdermatopathology.com
a low risk of progression and distant dissemination, especially in the context of negative sentinel lymph nodes biopsy.8 Additionally, the presence of an isolated cutaneous metastasis of few years duration with no evidence of other metastasis would be highly improbable and therefore incompatible with a metastatic etiology of the skin tumor. In our opinion, however, the ultimate evidence of the separate origin of both tumors came from a histopathology demonstrating an in situ component of EMPSGC denoting a primary cutaneous proliferation.3,9 This was accomplished even before the breast tumor was biopsied and facilitated by using immunohistochemical markers to highlight a layer of myoepithelial cells surrounding tumor nests.1,9,10 In summary, we describe a case of low-grade mucinous carcinoma of the breast detected in a patient previously diagnosed with primary cutaneous EMPSGC, a hitherto unreported cooccurrence. The correct diagnosis of tumors representing separate malignancies was made after careful pathology evaluation and clinicopathologic correlation. The histologic examination played a pivotal role in this process. The in situ component confirming primary cutaneous tumor has been evidenced by immunohistochemical identification of myoepithelial cells. EMPSGC has to be included
in the differential diagnosis of adnexal skin tumors detected in patients with mucinous visceral malignancies to avoid a potentially disastrous misdiagnosis of metastatic carcinoma. Jaroslaw Jedrych, Miroslawa Jones, Raja Seethala, Jonhan Ho,
MD* MD† MD† MD*
Departments of *Dermatology, and †Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
REFERENCES 1. Zembowicz A, Garcia CF, Tannous ZS, et al. Endocrine mucin-producing sweat gland carcinoma: twelve new cases suggest that it is a precursor of some invasive mucinous carcinomas. Am J Surg Pathol. 2005;29:1330–1339. 2. Mehta S, Thiagalingam S, Zembowicz A, et al. Endocrine mucin-producing sweat gland carcinoma of the eyelid. Ophthal Plast Reconstr Surg. 2008;24:164–165. doi: 10.1097/ IOP.0b013e3181659c96. 3. Flieder A, Koerner FC, Pilch BZ, et al. Endocrine mucin-producing sweat gland carcinoma: a cutaneous neoplasm analogous to solid papillary carcinoma of breast. Am J Surg Pathol. 1997;21:1501–1506. 4. Koike T, Mikami T, Maegawa J, et al. Recurrent endocrine mucin-producing sweat gland carcinoma in the eyelid. Australas J Dermatol. 2013;54:e46–e49. 5. Hoguet A, Warrow D, Milite J, et al. Mucinproducing sweat gland carcinoma of the eyelid: diagnostic and prognostic considerations. Am J Ophthalmol. 2013;155:585–592 e2.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 5, May 2015
6. McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ. 2000;321: 624–628. 7. Andersson I, Aspegren K, Janzon L, et al. Mammographic screening and mortality from breast cancer: the Malmo mammographic screening trial. BMJ. 1988;297: 943–948. 8. Diab SG, Clark GM, Osborne CK, et al. Tumor characteristics and clinical outcome of tubular and mucinous breast carcinomas. J Clin Oncol. 1999;17:1442–1448. 9. Kazakov DV, Suster S, LeBoit PE, et al. Mucinous carcinoma of the skin, primary, and secondary: a clinicopathologic study of 63 cases with emphasis on the morphologic spectrum of primary cutaneous forms: homologies with mucinous lesions in the breast. The Am J Surg Pathol. 2005;29: 764–782. 10. Dhaliwal CA, Torgersen A, Ross JJ, et al. Endocrine mucin-producing sweat gland carcinoma: report of two cases of an underrecognized malignant neoplasm and review of the literature. Am J Dermatopathol. 2013; 35:117–124.
Perivascular Basophilic Rim as a Histopathological Clue of Cutaneous Pseudomona aeruginosa Sepsis To the Editor: Ecthyma gangrenosum represents a formidable skin sign of the potentially life-threatening systemic infection caused by Pseudomonas aeruginosa (PA). Early diagnosis is vital in the management of PA sepsis. Clinical and histological skin manifestations of ecthyma gangrenosum occur with some variation of appearance, depending on the course of the lesion when it was first observed.1 We describe an immunosuppressed patient with multiple cutaneous lesions by PA sepsis. A 74-year-old man, a known case of large B-cell lymphoma stage IV-A, presented with fever, weakness, and fatigue 8 days after the third chemotherapy cycle. Physical examination revealed a pale and cachectic appearance. Oral temperature was 38.9°C. Thorax x-ray showed condensation in the right upper lobe. Blood analysis The authors declare no conflicts of interest.
Letters to the Editor
FIGURE 1. Intraepidermal vesicles and bullae, blood extravasation, and perivascular basophilic rings (H&E ·100). Detail of perivenular basophilic ring (bottom left corner) (H&E ·200).
revealed pancytopenia. The following day, physical examination showed 9 small, sparse, purplish patches in the patient’s trunk. Blood, urine, stool, and skin cultures were obtained. A skin biopsy was performed and revealed epidermal necrosis with vesicles and bullae, extensive extravasation of red blood cells into the dermis, and some superficial skin vessels with fibrinoid necrosis, but without inflammatory infiltration or thrombi. A perivascular basophilic rim was noted (Fig. 1). Gram stain revealed gram-negative bacilli concentrated at the adventitia of venules and scattered among the collagen
bundles in the dermis and the panniculus adiposus (Fig. 2). Blood and cutaneous cultures grew PA, sensitive to meropenem. The patient received intensive antibiotic treatment and supportive measures, but he developed multiple organ dysfunction syndrome and died 2 days later. The definition of septic vasculopathy is confusing. Histopathologically speaking, septic vasculitis is a thrombo-occlusive vasculopathy with variable morphology. Recently, septic vasculopathy has been defined as the occurrence of the following vascular changes: vessel wall neutrophil infiltration, edema, leukocytoclasis,
FIGURE 2. Gram-negative bacilli around the vessels (gram ·100). In the bottom left corner, gram-negative bacilli sparse the intima (arrows) (gram ·400).
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.amjdermatopathology.com |
427
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
